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Purpose Metformin combined with the mTOR inhibitor rapamycin showed potential synergistic anti-tumor activity in preclinical studies in pancreatic ductal adenocarcinoma (PDA). This phase 1b study (NCT02048384) was conducted to evaluate the feasibility and activity of metformin +/- rapamycin in the maintenance setting for unselected patients with metastatic PDA (mPDA) treated with chemotherapy. Materials and methods Eligible patients with stable or responding mPDA after ≥ 6 months on chemotherapy were randomized 1:1 to metformin alone (Arm A) or with rapamycin (Arm B), stratified by prior treatment with FOLFIRINOX. Fluorodeoxyglucose (FDG) PET scans and peripheral blood mononuclear cells were obtained for exploratory analyses. Results 22 subjects (11 per arm) received treatment per protocol. Median PFS/OS were 3.5 and 13.2 months respectively, with 2 year OS rate of 37%; there were no differences between arms. No responses were observed by RECIST; however, decreases in FDG avidity and/or CA19-9 were observed in several long-term survivors. Treatment related adverse events of Grade ≥ 3 occurred in 0% vs 27% of patients in Arm A vs B and were asymptomatic hematologic or electrolyte abnormalities that were not clinically significant. Improved survival was associated with low baseline neutrophil: lymphocyte ratio, baseline lack of assessable disease by PET, and greater expansion of dendritic cells following treatment. Conclusions Metformin +/- rapamycin maintenance for mPDA was well-tolerated and several patients achieved stable disease associated with exceptionally long survival. Further prospective studies are needed to clarify the role of these agents in the maintenance setting and to enhance patient selection for such approaches.

726 Background: The development of new treatments in oncology is a long, costly, and, too often, unsuccessful process. Methods for screening agents earlier in development and strategies for conducting smaller randomized controlled trials are needed. Methods: We used a mathematical model of tumor growth kinetics fit to serial radiographic tumor measurements or CA19-9 values to estimate rates of exponential tumor growth [g] and decay [d] during treatment for pancreatic ductal adenocarcinoma (PDAC). Results: We retrospectively collected and analyzed data from 2691 patients with stage III-IV PDAC who were enrolled in five clinical trials or were included in two large real-world data sets from Columbia University Irving Medical Center and Veterans Administration Medical Centers. Using log-rank comparison of Kaplan-Meier plots by quartile of g, we found that in patients with metastatic PDAC g correlates highly with overall (OS) and progression-free survival (PFS) (p

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by stromal fibrosis, hypoxia, and nutritional deprivation. PDAC tumors grow aggressively, diagnosis is typically made after metastasis and the disease remains associated with poor outcomes. The triplet chemotherapy regimen of gemcitabine, nab-paclitaxel with cisplatin was associated with a median overall survival of 16.4 months in patients with metastatic pancreatic cancer in the first-line setting (Jameson et al., 2020). Nutritional, metabolic interventions offer an opportunity to fundamentally change the tumor microenvironment and improve outcomes for patients. A medically supervised ketogenic diet (MSKD) defined as lower carbohydrate, lower protein, and higher fat can significantly reduce glucose and insulin and increase metabolically active ketone bodies. A ketogenic diet combined with triplet chemotherapy (gemcitabine, nab-paclitaxel, cisplatin) was shown to inhibit murine pancreatic KPC tumor growth and to triple the survival benefit of chemotherapy alone. The ketogenic diet combined with triple chemotherapy was associated with glucose depletion, altered TCA substrate usage, and NADH elevation. Methods: In this Phase II randomized clinical trial (NCT04631445), we are evaluating a medically supervised ketogenic diet (MSKD) versus a standard diet when combined with the triplet therapy in patients with treatment-naive advanced pancreatic cancer. The primary endpoint is progression free survival for triplet therapy while on MSKD or non-MSKD. Secondary endpoints include disease control rate (PR+ CR+ SD for at least 9 weeks), change in CA 19-9 (or CA125, or CEA if not expressers of CA 19-9), average insulin levels, HbA1c, body weight, a comparison of gut microbial diversity, changes in serum metabolites and quality of life via the EORTC QLQ-C30 assessment. Unlike prior ketogenic intervention studies, the MSKD is being supported by a continuous care nutrition intervention through Virta Health Corp, that offers tracking of daily ketone and glucose levels, a web-based software application, education, and communication with a remote care team to ensure sustained nutritional ketosis. A total of 40 patients with untreated metastatic PDAC are planned for enrollment, 20 randomized to each arm. The trial opened for accrual November 2020. Citation Format: Diana Hanna, Gayle S. Jameson, Drew W. Rasco, Angela Alistar, Richard C. Frank, Anthony B. El-Khoueiry, Julia E. Wiedmeier, Caroline Roberts, Brandon Fell, Sarah Hallberg, Denise Roe, Derek Cridebring, Joshua Rabinowitz, Stephen Thomas Gately, Daniel D. Von Hoff. Randomized Phase II trial of two different nutritional approaches for patients receiving treatment for their advanced pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT549.

TPS637 Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by stromal fibrosis, hypoxia, and nutritional deprivation. PDAC tumors grow aggressively, diagnosis is typically made after metastasis and the disease remains associated with poor outcomes. The triplet chemotherapy regimen of gemcitabine, nab-paclitaxel with cisplatin was associated with a median overall survival of 16.4 months in patients with metastatic pancreatic cancer in the first-line setting (Jameson et al., 2020). Nutritional, metabolic interventions offer an opportunity to fundamentally change the tumor microenvironment and improve outcomes for patients. A ketogenic diet defined as lower carbohydrate, lower protein, and higher fat can significantly reduce glucose and insulin and increase metabolically active ketone bodies and has been evaluated in patients with a variety of solid tumors (Weber et al, 2020). Recently, a ketogenic diet combined with triplet chemotherapy was shown to inhibit murine pancreatic KPC tumor growth and significantly prolong animal survival over chemotherapy alone. Tumor growth inhibition was associated with glucose depletion, altered TCA substrate usage, and NADH elevation. Methods: In this Phase II randomized clinical trial (NCT04631445), we are evaluating a medically supervised ketogenic diet (MSKD) versus a standard diet when combined with the triplet therapy in patients with treatment-naive advanced pancreatic cancer. The primary endpoint is progression free survival for triplet therapy while on MSKD or non-MSKD. Secondary endpoints include disease control rate (PR+ CR+ SD for at least 9 weeks), change in CA 19-9 (or CA125, or CEA if not expressers of CA 19-9), average insulin levels, HbA1c, body weight, a comparison of gut microbial diversity, changes in serum metabolites and quality of life via the EORTC QLQ-C30 assessment. Unlike prior ketogenic intervention studies, the MSKD is being supported by a continuous care nutrition intervention through Virta Health Corp, that offers tracking of daily ketone and glucose levels, a web-based software application, education, and communication with a remote care team to ensure sustained nutritional ketosis. A total of 40 patients with untreated metastatic PDAC are planned for enrollment, 20 randomized to each arm. The trial opened for accrual November 2020. Clinical trial information: NCT04631445.

Background: Increasing evidence suggests that high concentrations of AA (vitamin C) can decrease the growth of aggressive tumors, including Ras-mutant tumors. Based on the unmet need in MPC, its high frequency of Ras mutations, and prior work combining PP +C +G in pts with MPC (response rate of 70.5%, median survival 16.4 mos), we explored the addition of AA to that regimen. Pre and post treatment biopsies for biomarkers and digital spacial profiling are also being performed. Methods: This pilot trial utilized a 3 + 3 design for dose escalation of AA. Eligibility criteria included untreated stage IV MPC, ECOG 0-1, and measurable disease. Excluded were pts with a G6PD deficiency, renal oxalate stones, or need of capillary blood glucose monitoring as AA causes false low readings. The primary objective of the phase 1b was to determine the maximum tolerated dose (MTD) of AA in combination with PP +C +G in pts with MPC. Exploratory objectives included analysis of tumor texture on radiologic scans as an imaging biomarker for response; correlation between peak plasma levels of AA and response to treatment; potential biomarkers in the tumor including tumor immune cell infiltration, stromal activation, stem call enumeration; change in numbers of circulating tumor stem cells and macrophage lineage changes. Results: As of 7/2021, the phase Ib enrollment in this study has been completed. Six pts were treated in the cohort of AA 25 gm/m2, 4 pts at AA 37.5 gm/m2, and 7 pts at 56.25 gm/m2. The majority of all reported AEs were grades 1-2. The most common AEs related to study treatment were: platelet count decrease (70.6%), diarrhea (70.6%), hypomagnesemia (52.9%), dysgeusia (47.1%), peripheral sensory neuropathy (47.1%), nausea (35.3%), fatigue (35.3%), neutrophil count decreased (35.3%), and hypokalemia (35.3%). Of the 17 pts enrolled, 15 were evaluable. Response by RECIST 1.1 is 11 PR (73.3%), 2 SD (13.3%), 2 PD (13.3%). Evaluation of median PFS and OS is ongoing. Conclusions: This study has a high response rate of 73%. Most pts in all AA dosing cohorts experienced a brisk response to therapy. AA did not appear to add toxicities compared to historical AE data of PP +C +G and was well tolerated in all dose cohorts. The MTD of AA was not reached in the 56.25 gm/m2 cohort. The protocol allowed for an additional dose escalation of AA to 75 gm/m2. However, all pts in the 56.25 gm/m2 cohort achieved our goal of peak plasma AA levels of > 20 mM so the study was closed to enrollment. Quality of life measures, tumor tissue and blood sample analyses are underway. Supported by SU2C, Cancer Research UK, Lustgarten Foundation, Destroy Pancreatic Cancer & the Young family. Citation Format: Gayle S. Jameson, Erkut H. Borazanci, Daniel D. Von Hoff, Joshua D. Rabinowitz, Michael S. Gordon, Sarah D. LeGrand, Courtney Snyder, Karen Ansaldo, Denise J. Roe, Haiyong Han. A phase Ib/II trial of high dose ascorbic acid (AA) + paclitaxel protein bound (PP) + cisplatin (C) + gemcitabine (G) in patients (pts) with previously untreated metastatic pancreatic cancer (MPC) [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-015.

Background: Effective therapy for the treatment of PDAC remains one of the greatest unmet oncology clinical needs. The addition of C to G and AP has shown 71% ORR in a previously reported study [JAMA Oncol. 2019 Oct 3;6(1):125-32]. In preclinical work, vitamin D (Vit D) analog therapy decreases myeloid derived suppressor cells and regulatory T cells, turning PDAC into a more immune favorable microenvironment. This trial combines AP/C/G with Vit D analog P and the anti-PD-1 antibody N as a combination therapy for patients with previously untreated metastatic PDAC. This trial evaluates the efficacy and safety of NAPPCG in that patient population (NCT02754726). Methods: Eligibility criteria include Stage IV PDAC, no prior chemotherapy for systemic disease, KPS ≥ 70, and RECIST 1.1 measurable disease. Doses are AP 125 mg/m2, G 1000 mg/m2, each infused over 30 minutes with C 25 mg/m2 infused over 60 minutes on days 1, 8, 22, and 29 of a 42-day cycle. N is given at a fixed dose of 240 mg as a 60 minute infusion on days 1, 15, and 29. P is given at a fixed dose of 25 µg IV twice weekly. Primary objective was to determine the efficacy of the combination for patients with previously untreated metastatic PDAC through determining CR, ORR, PFS, and OS. The secondary objective was to evaluate safety in patients with previously untreated metastatic PDAC. Exploratory endpoints include evaluating tissue molecular profile as it relates to treatment outcomes. Results: Trial was conducted May 2016 with enrollment completed August 2020. 35 patients have been enrolled in the study and 32 are evaluable (baseline and ≥1 follow up CT scan). Most common drug-related grade (Gr) 3-4 adverse events (AE’s), are thrombocytopenia 76% (gr 3 = 34%, gr 4 = 28%) with no serious bleeding events, anemia 37% (gr 3 = 37%, gr 4 = 0%), and CIPN 11% (gr 3 = 11%, gr 4 = 0%). Immune Related Adverse Events >5% were colitis (gr 3=8.6%, gr 4= 0%) and dermatitis (gr 3=8.6%, gr 4= 0%). By RECIST 1.1 criteria, the best response is 1 CR, 26 PR, 4 SD, 1 PD, yielding an 84% ORR (95% CI = (67%, 95%). Median PFS is 6 months (95% CI = (5, 8)). Median OS is 18 months (95% CI = (13, 22)). Conclusions: Although a small study, the high response rate is encouraging. Evaluation of exploratory endpoints is ongoing. Pursuing this regimen in localized PDAC is warranted due to its high ORR. Supported by grants from the Seena Magowitz Foundation, Mattress Firm, Bristol Myers Squibb, and SU2C. Citation Format: Erkut Borazanci, Gayle S. Jameson, Sunil Sharma, Frank Tsai, Ronald L. Korn, Lana Caldwell, Karen Ansaldo, David T. Ting, Denise Roe, Anna Bermudez, Daniel D. Von Hoff. A phase II pilot trial of nivolumab (N) + albumin bound paclitaxel (AP) + paricalcitol (P) + cisplatin (C) + gemcitabine (G) (NAPPCG) in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC) [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PR-002.

Background: Pancreatic ductal adenocarcinoma (PDA) is a lethal cancer with complex genomes and dense fibrotic stroma. This study was designed to identify clinically relevant somatic aberrations in pancreatic cancer genomes of patients with primary and metastatic disease enrolled and treated in two clinical trials. Methods: Tumour nuclei were flow sorted prior to whole genome copy number variant (CNV) analysis. Targeted or whole exome sequencing was performed on most samples. We profiled biopsies from 68 patients enrolled in two Stand Up to Cancer (SU2C)-sponsored clinical trials. These included 38 resected chemoradiation naïve tumours (SU2C 20206-003) and metastases from 30 patients who progressed on prior therapies (SU2C 20206-001). Patient outcomes including progression-free survival (PFS) and overall survival (OS) were observed. Results: We defined: (a) CDKN2A homozygous deletions that included the adjacent MTAP gene, only its’ 3′ region, or excluded MTAP; (b) SMAD4 homozygous deletions that included ME2; (c) a pancreas-specific MYC super-enhancer region; (d) DNA repair-deficient genomes; and (e) copy number aberrations present in PDA patients with long-term (⩾ 40 months) and short-term (⩽ 12 months) survival after surgical resection. Conclusions: We provide a clinically relevant framework for genomic drivers of PDA and for advancing novel treatments.

Purpose: To determine whether deposition characteristics of ferumoxytol (FMX) iron nanoparticles in tumors, identified by quantitative MRI, may predict tumor lesion response to nanoliposomal irinotecan (nal-IRI).Experimental Design: Eligible patients with previously treated solid tumors had FMX-MRI scans before and following (1, 24, and 72 hours) FMX injection. After MRI acquisition, R2* signal was used to calculate FMX levels in plasma, reference tissue, and tumor lesions by comparison with a phantom-based standard curve. Patients then received nal-IRI (70 mg/m2 free base strength) biweekly until progression. Two percutaneous core biopsies were collected from selected tumor lesions 72 hours after FMX or nal-IRI.Results: Iron particle levels were quantified by FMX-MRI in plasma, reference tissues, and tumor lesions in 13 of 15 eligible patients. On the basis of a mechanistic pharmacokinetic model, tissue permeability to FMX correlated with early FMX-MRI signals at 1 and 24 hours, while FMX tissue binding contributed at 72 hours. Higher FMX levels (ranked relative to median value of multiple evaluable lesions from 9 patients) were significantly associated with reduction in lesion size by RECIST v1.1 at early time points (P < 0.001 at 1 hour and P < 0.003 at 24 hours FMX-MRI, one-way ANOVA). No association was observed with post-FMX levels at 72 hours. Irinotecan drug levels in lesions correlated with patient's time on treatment (Spearman ρ = 0.7824; P = 0.0016).Conclusions: Correlation between FMX levels in tumor lesions and nal-IRI activity suggests that lesion permeability to FMX and subsequent tumor uptake may be a useful noninvasive and predictive biomarker for nal-IRI response in patients with solid tumors. Clin Cancer Res; 23(14); 3638–48. ©2017 AACR.

Summary Background Further optimisation of present standard chemoradiation is needed in patients with locally advanced rectal cancer. Veliparib, an oral poly(ADP-ribose) polymerase inhibitor, has been shown to enhance the antitumour activity of chemotherapy and radiotherapy in preclinical models. We aimed to establish the maximum tolerated dose and establish the recommended phase 2 dose of veliparib combined with neoadjuvant capecitabine and radiotherapy. Methods This phase 1b, open-label, multicentre, dose-escalation study was done at six hospitals (one in Australia and five in the USA). Patients were eligible if they were aged 18 years or more and were newly diagnosed with stage II to III locally advanced, resectable adenocarcinoma of the rectum with a distal tumour border of less than 12 cm from anal verge. Patients were ineligible if they had received anticancer therapy or surgery (except colostomy or ileostomy) 28 days or less before the first dose of study drug, previous pelvic radiotherapy, or previous treatment with poly (ADP-ribose) polymerase inhibitors. Enrolled patients received capecitabine (825 mg/m 2 orally twice daily) with radiotherapy (50·4 Gy in 1·8 Gy fractions daily, approximately 5 days consecutively per week for about 5·5 weeks). Veliparib (20–400 mg orally twice daily) was administered daily starting on day 2 of week 1 and continuing until 2 days after radiotherapy completion. Patients underwent total mesorectal excision 5–10 weeks after radiotherapy completion. The primary objectives were to establish the maximum tolerated dose and recommended phase 2 dose of veliparib plus capecitabine and radiotherapy, with an exposure-adjusted continual reassessment methodology. Efficacy and safety analyses were done per protocol. The reported study has completed accrual and all analyses are final. This trial is registered with ClinicalTrials.gov, number NCT01589419. Findings Between June 12, 2012, and Jan 13, 2015, 32 patients received veliparib (22 in the dose-escalation group; ten in the safety expansion group); 31 were assessable for efficacy ( Interpretation Veliparib plus capecitabine and radiotherapy had an acceptable safety profile and showed a dose-proportional pharmacokinetic profile with no effect on the pharmacokinetics of capecitabine. Preliminary antitumour activity warrants further evaluation. Funding AbbVie Inc.

IMPORTANCE: Genomes of metastatic pancreatic cancers frequently contain intrachromosomal aberrations, indicating a DNA repair deficiency associated with sensitivity to DNA damaging agents, such as platinum. OBJECTIVE: To determine response rate following treatment with nab-paclitaxel plus gemcitabine plus platinum-based cisplatin for patients with metastatic pancreatic ductal adenocarcinoma (PDA). DESIGN, SETTING, AND PARTICIPANTS: This was a single-arm, open-label, phase 1b/2 clinical trial of nab-paclitaxel plus gemcitabine plus cisplatin treatment in which 25 patients with previously untreated metastatic PDA were enrolled. The trial was conducted from December 2013 to July 2016 at 3 US sites, with the last patient receiving study treatment at the end of October 2016, and the study closing January 2018. INTERVENTIONS: Patients were treated with nab-paclitaxel plus gemcitabine plus various doses of cisplatin, 25 mg/m(2), 37.5 mg/m(2), and 50 mg/m(2), on days 1 and 8 of a 21-day cycle. MAIN OUTCOMES AND MEASURES: Primary end point was complete response rate as assessed by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST), and levels of carbohydrate antigen 19-9 (or in nonexpressers, carbohydrate antigen 125 or carcinoembryonic antigen). Efficacy analysis included evaluable patients (those who received at least 1 dose of study treatment and had at least 1 postbaseline tumor assessment). RESULTS: Of 25 patients enrolled in the study, the median (range) age was 65.0 (47.0-79.0) years, 14 (56%) were men, and most (24) were white (96%). The maximum tolerable dose of cisplatin was 25 mg/m(2). The most common treatment-related adverse events grade 3 or higher were thrombocytopenia (17 patients [68%]), anemia (8 patients [32%]), and neutropenia (6 patients [24%]). Fatal events occurred for 3 patients (12%); 2 were related to study participation. A median (range) of 8 (1-15) cycles was completed. The RECIST responses in 24 evaluable patients included 2 complete responses (8%), which was below the primary end point of 25%, 15 partial responses (62%), 4 stable disease (17%), and 3 progressive disease (12%), with median overall survival of 16.4 (95% CI, 10.2-25.3) months; 16 patients (64%) were alive at 1 year, 10 (40%) at 2 years, 4 (16%) at 3 years, and 1 (4%) at 4 plus years. Overall survival ranged from 36 to 59 months. Median progression-free survival was 10.1 (95% CI, 6.0-12.5) months. Thus, the overall response rate was 71%, and the disease control rate was 88%. CONCLUSIONS AND RELEVANCE: This triple drug regimen showed substantial clinical activity in this small study. Although the primary end point was not reached, the high overall response rate, disease control rate, and median survival time among patients with advanced PDA treated with this combination are encouraging. The regimen is being studied in patients with PDA in the neoadjuvant setting and in patients with advanced biliary cancers. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01893801

Purpose Improvements in systemic treatment have led to a prolongation of survival and quality of life in patients with metastatic tumors in recent years. However, despite this improved standard of care, it is expected that the progression-free survival (PFS) for patients with refractory cancers will continue to decline over subsequent therapy lines. In those patients, studies and meta-analyses showed that treatment based on multiplatform molecular profiling (MMP) of tumor tissue may derive a clinical benefit. The aim of this study was to analyze if molecular-based therapy may prolong PFS compared with the PFS of the immediately prior therapy. Methods We pooled clinical data of 140 patients treated within 3 recently conducted pilot studies and included an additional 21 patients who were treated within the ongoing ONCO-T-PROFILE program. The PFS of the molecular-based treatment was compared with the PFS of the previous therapy using Kaplan-Meier curves. Results In heavily pretreated cancer patients, the PFS could be significantly improved using molecular-based treatment options (120.0 vs. 89.5 days). More than 50% of patients showed a clinical benefit from MMP-guided therapy as defined by a PFS ratio of 1.3 or greater. Conclusions We conclude that pretreated cancer patients can benefit from incorporation of molecular profiling, as demonstrated by not only an increase of the PFS ratio but also PFS. Further randomized trials in specific tumor subtypes may help establish specific patient populations who might benefit most from MMP guidance.

Background Molecular analysis has revealed four subtypes of pancreatic ductal adenocarcinoma (PDAC). One subtype identified for the presence of DNA damage repair deficiency can be targeted therapeutically with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib. We performed a single institution retrospective analysis of treatment response in patients with PDAC treated with olaparib who have DNA damage repair deficiency mutations. Subjects, Materials, and Methods Patients with germline or somatic mutations involving the DNA repair pathway were identified and treated with olaparib. The primary objective was to examine the objective response rate (ORR). The secondary objectives were assessing tolerability, overall survival, and change in cancer antigen 19-9. Quantitative texture analysis (QTA) was evaluated from CT scans to explore imaging biomarkers. Results Thirteen individuals with metastatic PDAC were treated with Olaparib. The ORR to Olaparib was 23%. Median overall survival (OS) was 16.47 months. Four of seven patients with BRCA mutations had an effect on RAD51 binding, with a median OS of 24.60 months. Exploratory analysis of index lesions using QTA revealed correlations between lesion texture and OS (hepatic lesion tumor texture correlation coefficient [CC], 0.683, p = .042) and time on olaparib (primary pancreatic lesion tumor texture CC, 0.778, p = .023). Conclusion In individuals with metastatic PDAC who have mutations involved in DNA repair, Olaparib may provide clinical benefit. BRCA mutations affecting RAD51 binding domains translated to improved median OS. QTA of individual tumors may allow for additional information that predicts outcomes to treatment with PARP inhibitors.

e16720 Background: Pancreatic cancer (PC) is the third most lethal form of cancer in the United States, and is most often diagnosed having already metastasized, making its 5-year survival rate one of the lowest. Metastatic PC (mPC) is most common at sites such as liver, lymph nodes, and lung while, in contrast, brain metastases from PC are rare. Brain metastases present a major challenge for future oncological research, as they are difficult to treat. If PC patients most likely to develop brain metastases can be identified earlier, there is an opportunity for rapid therapeutic intervention. There is limited research and understanding of the relationship between pancreatic cancer and brain metastases. Methods: We performed a retrospective, non-interventional study using deidentified data. Inteliquet’s data was aggregated from its consortium of 175 US healthcare locations, which includes a variety of source systems at each site. These sources include electronic medical record systems, laboratory information management systems, and other sources. A subset of the adult mPC data originally treated at HonorHealth was identified as an exploratory cohort. Results: 833 patient records were identified with drug treated mPC, 33 (4%) of which had metastasized to the brain. The PC dataset had a median diagnosis age of 65 and was 46% female. The site of the primary tumor within the pancreas was acquired from ICD10 code: 35% were in the head, 14% in the tail, 15% in the body, 5% in overlapping sites, 6% in other parts and 26% where location was unspecified. Metastatic locations came from secondary malignancy ICD10 codes: 63% had liver and 25% had lung metastases, which aligns with prior studies. For patients with brain metastases, the gender distribution was 42% female, while the distribution of primary PC site was: 33% head, 9% tail, 6% body, 6% in overlapping locations, 12% in other parts and 33% with unspecified location. The median age of diagnosis in the brain metastasis group was 67 years. Conclusions: This is the largest study of PC patients with brain metastases that we could find. 33 patients out of 833 had brain metastases compared to a recent review which had 25 cases. Our data suggests that specification of the primary pancreatic site is more difficult, aside from the head of the pancreas. Analyses are underway to explore correlations between other clinical factors and brain metastases, and to calculate the time in between the initial pancreatic cancer diagnosis and detection of the brain metastasis. This hypothesis-generating cohort will be tested in patient data from the rest of the consortium.

4631 Background: Localized PDAC management has recently evolved. Due to concerns over micro metastases at diagnosis the use of neoadjuvant chemotherapy for PDAC has become more common. Typical therapies involve the use of multiagent systemic chemotherapies with or without radiation therapy. In retrospective studies, Cancer Antigen 19-9 (CA 19-9) normalization in borderline resectable (BR) and locally advanced (LA) PDAC has been associated with greater OS. The addition of cisplatin (C) to gemcitabine (G) and paclitaxel protein bound (A), has shown promising clinical data in a previously reported study in advanced PDAC [JAMA Oncol. 2020;6(1):125-132]. We conducted a prospective, phase 2 clinical trial of patients with resectable (R), BR, and LA PDAC utilizing a regimen combining A + G + C + paricalcitol (P) with the primary endpoint of CA 19-9 normalization (NCT03138720). Methods: Eligibility criteria include patients with histologically confirmed R, BR, or LA PDAC, elevated CA 19-9, and a KPS ≥ 70% with normal end organ function. Doses are A 125 mg/m2, G 1000 mg/m2, C 25 mg/ m2, P at a fixed dose of 25 µg on days 1, 8 of a 21-day cycle (all treatment IV). Primary objective is to evaluate CA 19-9 normalization with the neoadjuvant chemotherapy. Secondary objectives are to assess R0 rate, pathologic complete response (pCR), safety and tolerability, radiologic response rate, and 2 year overall survival (OS) from date of study entry. Exploratory objectives include evaluating imaging biomarkers and vascular involvement by tumor in relation to therapy. Results: To date 24 of the planned 24 patients have been enrolled. 13 male, 11 female; age range 49 to 84 yo. Patient classifications is 8 R; 7 BR; 9 LAPC. Median baseline CA 19-9 156 (range 45-3674). Most common drug related grade (gr) 3-4 adverse events (AEs) are: thrombocytopenia gr 3 29%, gr 4 25%, anemia gr 3 45.8%, gr 4 4.2%, and hypophosphatemia gr 3 8.3%. CA 19-9 normalization occurred in 50% (12/24) who have completed at least 1 cycle of treatment. To date, 14 individuals went to surgery, with 13/14 achieving R0, (1 pCR). Overall response rate in measurable patients is 38% (1 CR, 8 PR). Median OS and 2-year survival data are not yet matured. Conclusions: In patients with non-metastatic PDAC, the use of A+G+C+P resulted in a CA 19-9 normalization rate in 50% of individuals. The study is ongoing and OS data is maturing. Clinical trial information: NCT03138720 .

Introduction: Based on the unmet medical need in MPC, its high frequency of Ras mutations, and prior work combining PP + C + G demonstrating an objective response rate of 70.5% in 24 pts with MPC with a median survival of 16.4 mos (J Clin Oncol 2017;35 [suppl 4S; abstract 341]), we are exploring the addition of HD AA to PP + C + G (#NCT03410030). Background: Increasing evidence suggests that HD AA (vitamin C) can decrease the growth of aggressive tumors, including Ras-mutant tumors, by inducing oxidative stress (Chen et al., PNAS 2008; Yun et al., Science 2015; Shoenfeld et al., Cancer Cell 2017). Despite the potential to produce toxic radicals, high-dose AA has generally been well tolerated in animals and humans, including in combination with chemotherapy. Methods: This phase Ib/II trial uses a 3 + 3 dose escalation of AA. Eligibility criteria include pts with previously untreated stage IV MPC, ECOG 0-1, and measurable disease. Excluded are pts with a G6PD deficiency, history of renal oxalate stones, and need of frequent capillary blood glucose monitoring as AA causes false low readings. Doses are PP 125 mg/m2, G 1000 mg/m2, C 25 mg/ m2 on days 1 and 8 of each 21-day cycle. AA infusions are given on days 1, 3, 8, 10, 15, and 17 every 21 days. We plan on studying up to 4 dose levels of AA including 25, 37.5, 56.25, and 75 gm/m2, seeking to determine the recommended phase 2 dose (RP2D). Tissue analysis is being done on pre- and optional post-treatment tumor biopsies. Primary objective(s): phase Ib—to determine the maximum tolerated dose (MTD) and RP2D of AA with PP + C + G; phase II—to determine the efficacy (disease control rate of CR+ PR+ SD x 18 weeks) of the combination at the RP2D in pts with MPC. Exploratory objectives include quantitative textural analysis, correlation between peak plasma levels of AA and treatment response, and potential biomarkers in the tumor. Planned sample size is up to 24 pts in phase Ib and up to 21 pts in phase II. Results: As of 6/23/19, 9 pts have been treated. Grade (gr) ≥ 3 treatment-related adverse events are thrombocytopenia, gr 3 (44%), gr 4 (11%) with no serious bleeding events; neutropenia gr 3 (22%); anemia gr 3 (22%); hypokalemia gr 3 (22%); diarrhea gr 3 (11%); hypomagnesemia gr 3 (11%); and hypophosphatemia gr 3 (11%). In the 7 response-evaluable pts (baseline and ≥ 1 follow-up CT scan), all pts have experienced a disease response to therapy with substantial decrease in tumor size and decline in tumor markers. It is too early in the trial to determine complete and partial response rates. Conclusion: Through the first two dose levels of AA we have observed good tolerability and preliminary evidence of high levels of antitumor activity. Dose escalation is continuing. (Supported by SU2C, Cancer Research UK, Lustgarten Foundation & Destroy Pancreatic Cancer.) Citation Format: Gayle S. Jameson, Erkut H. Borazanci, Joshua Rabinowitz, Karen Ansaldo, Sarah LeGrand, David Propper, Courtney Snyder, Michael Gordon, Denise Roe, Daniel D. Von Hoff. A phase Ib/II trial of high-dose (HD) ascorbic acid (AA) + paclitaxel protein bound (PP) + cisplatin (C) + gemcitabine (G) in patients (pts) with metastatic pancreatic cancer (MPC) [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B27.

Background: Localized PDAC management has recently evolved. Due to concerns over micrometastases at diagnosis, the use of neoadjuvant chemotherapy for PDAC has become more common. Typical therapies involve the use of multiagent systemic chemotherapy with or without radiation therapy. Cancer antigen 19-9 (CA 19-9) normalization in borderline resectable (BR) and locally advanced (LA) PDAC has been associated with greater OS. The addition of cisplatin (C) to gemcitabine (G) and paclitaxel protein bound (A) has shown promising clinical data in a previously reported study in advanced PDAC (J Clin Oncol 2017;35:suppl 4S; abstract 341). We conducted a prospective, phase 2 clinical trial of patients with resectable, BR, and LA PDAC utilizing a regimen combining A + G + C + paricalcitol (P) with the primary endpoint of CA 19-9 normalization (NCT03138720). Methods: Eligibility criteria include patients with histologically confirmed resectable, BR, or LA PDAC, elevated CA 19-9, and a KPS ≥ 70% with normal end organ function. Doses are A 125 mg/m2, G 1000 mg/m2, C 25 mg/ m2, P at a fixed dose of 25 μg on days 1, 8 of a 21-day cycle (all treatment IV). Primary objective is to evaluate CA 19-9 normalization with the neoadjuvant chemotherapy. Secondary objectives are to assess R0 rate, pathologic complete response (pCR), safety and tolerability, radiologic response rate, and 2-year overall survival (OS) from date of study entry. Exploratory objectives include evaluating imaging biomarkers and vascular involvement by tumor in relation to therapy. Results: To date, 21 of the planned 24 patients have been enrolled: 11 male, 10 female; age range 49 to 85 yo. Patient classifications are 7 R; 7 BR; 7 LAPC. Most common drug-related grade (gr) 3-4 adverse events (AEs) are thrombocytopenia gr 3 40%, gr 4 33%, anemia gr 3 60%, and hypophosphatemia 13%. Of the 21, 16 are evaluable for maximum percent decrease in CA 19-9. CA 19-9 normalization occurred in 44% (7/16) who have completed at least 1 cycle of treatment. To date, 9 individuals went to surgery, with 8/9 achieving R0 (no pCR). Overall response rate in measurable patients is 26% (4/15 PR). Median OS and 2-year survival data are not yet matured. Conclusions: In patients with nonmetastatic PDAC, the use of A+G+C+P resulted in a CA 19-9 normalization rate in 44% of individuals. The study is ongoing and OS data are maturing. (Supported by grants from the HonorHealth Foundation and Marley Foundation.) Citation Format: Erkut Borazanci, Gayle Jameson, Courtney Snyder, Frank Tsai, Michael Gordon, Sunil Sharma, Carol Guarnieri, Amar Thosani, Syed Rahmanuddin, Ronald Korn, Steven Sckolnik, Paula Sedivy, Susan Haag, Kevin Gosselin, Daniel Von Hoff, Albert Amini. Paclitaxel protein bound plus gemcitabine plus cisplatin and paricalcitol neoadjuvant therapy for localized pancreatic ductal adenocarcinoma (PDAC) [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B05.

Background: Pancreatic cancer remains a deadly disease, and immunotherapy is effective in only 1-2% of microsatellite instability-high pancreatic cancers. The response to immunotherapy is very heterogeneous across tumor types, but recently there is evidence that the gastrointestinal microbiome may influence the response to immunotherapy. The SU2C Catalyst Trial is a randomized phase II maintenance trial to compare outcomes using a combination regimen of the vitamin D agonist, paricalcitol, plus the PD-1 inhibitor pembrolizumab vs. pembrolizumab alone. As a part of this trial, we are examining the composition of the gut microbiome. Methods: Patients with metastatic pancreatic cancer receiving standard first-line chemotherapy are eligible after achieving best response of at least stable disease and are then randomized to pembrolizumab +/- paricalcitol groups. Patients remain on study treatment until disease progression or treatment-ending toxicities. Patients collect stool samples within 72 hours prior to day one of each cycle, 24-72 later, and ca. 30 days after treatment discontinuation. DNA is extracted from fecal samples and 16S rRNA gene libraries are generated targeting the V4 region of bacterial and archaeal rRNA gene. Libraries are sequenced on the Illumina MiSeq and sequence reads are analyzed using QIIME2. Results: To date, we have analyzed the gut microbiota of six patients who have completed between one to four cycles of study treatment. We identified 28 taxa that occurred at ≥5% relative abundance in any given patient. As is true for most microbiome studies, intersubject variation was much greater than intrasubject variation. However, in three patients, there was significant change in the composition of the microbial communities over time. One patient had a “healthy” microbiome across the one treatment cycle with a good balance of Bacteroidetes and Firmicutes and the presence of Faecalibacterium prausnitzii. This patient discontinued the study due to treatment-related hypophysitis Grade 2, which was resolved by prednisone treatment and remains in survival follow-up. One patient had a relatively healthy microbiome during cycle one and two, but the composition of the gut microbiome became severely dysbiotic at the time the patient discontinued study treatment due to disease progression; this patient died five months later. The remaining four patients were dysbiotic across all treatment times, with some having very low alpha diversity. Conclusions: The gut microbiota of pancreatic cancer patients in the SU2C trial was very heterogeneous and usually dysbiotic. In one patient, who survives progression free, a “healthy” microbiome was observed. This provides promise for future use of the gut microbiome as a predictor of response to immunotherapy for pancreatic cancer and the potential for modulating the gut microbiome to improve responses in patients with dysbiosis. (ClinicalTrials.gov Identifier: NCT03331562. Support: Stand Up To Cancer (SU2C) Catalyst Merck Grant.) Citation Format: Sarah K. Highlander, Vincent Chung, Angela T. Alistar, Erkut Borazanci, Gayle Jameson, Talima Pearson, Nina A. Cantafio, Daniel D. Von Hoff. Gastrointestinal microbiome changes in stage IV pancreatic cancer patients treated with pembrolizumab with or without paricalcitol on the Stand Up to Cancer (SU2C) Pancreas Catalyst Trial [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B24.

Background: The choice of a regimen in metastatic pancreatic cancer patients following progression on 1st line therapy is empiric and outcomes are unsatisfactory. This phase II study was performed to evaluate the efficacy of therapy selected by immunohistochemistry (IHC) in these patients following progression after one or more therapies. Methods: Eligible patients underwent a percutaneous biopsy of a metastatic lesion and treatment selection was determined by IHC. The study required 35 evaluable patients (power of 86%) for detecting a true 1-year survival rate of >20%. Results: A tumor biopsy was performed in 48 of 49 accrued patients. Study therapy was not given (n=13) either due to insufficient tumor on biopsy (n=8) or due to worsening cancer related symptoms after biopsy (n=5). The demographics of evaluable patients (n=35) are male/female (59%/41%), with age range 34–78 years (median 63 years). Patients had 1–6 prior regimens (median of 2). The most common IHC targets were topoisomerase 1 or 2, thymidylate synthase, excision repair cross-complementation group 1 protein (ERCC1), and osteonectin secreted protein acidic and rich in cysteine (SPARC). Commercially available treatment regimens prescribed included FOLFIRI, FOLFOX, irinotecan, and doxorubicin. The response (RECIST) was 9%, the median survival was 5.6 months (94% CI, 3.8–8.2), and the 1-year survival was 20% (95% CI, 7–33%). Conclusions: In all patients, IHC assays resulted in identification of at least two targets for therapy and a non-cross resistant regimen could be prescribed for therapy with evidence of some benefit. An IHC based treatment strategy is feasible and needs validation in larger studies.

Oncology Nursing Society (ONS) members share a unique passion for the people they serve and frequently commit to projects that make a difference. Camp Raising Spirits, a weekend retreat for adults with cancer, has made a difference in southwestern Pennsylvania for hundreds of people with cancer and their caregivers for 24 consecutive years. This article will describe how an ONS chapter capitalized on the leadership attributes of partnership, creativity, and commitment to sustain an important community service program. .

Background Pharmacological inhibition of polo-like kinase 1 (PLK1) represents a new approach for the treatment of solid tumors. This study was aimed at determining the first cycle dose-limiting toxicities (DLTs) and related maximum tolerated dose (MTD) of NMS-1286937, a selective ATP-competitive PLK1-specific inhibitor. Secondary objectives included evaluation of its safety and pharmacokinetic (PK) profile in plasma, its antitumor activity, and its ability to modulate intracellular targets in biopsied tissue. Methods This was a Phase I, open-label, dose-escalation trial in patients with advanced/metastatic solid tumors. A treatment cycle comprised 5 days of oral administration followed by 16 days of rest, for a total of 21 days (3-week cycle). Results Nineteen of 21 enrolled patients with confirmed metastatic disease received study medication. No DLTs occurred at the first 3 dose levels (6, 12, and 24 mg/m2/day). At the subsequent dose level (48 mg/m2/day), 2 of 3 patients developed DLTs. An intermediate level of 36 mg/m2/day was therefore investigated. Four patients were treated and two DLTs were observed. After further cohort expansion, the MTD and recommended phase II dose (RP2D) were determined to be 24 mg/m2/day. Disease stabilization, observed in several patients, was the best treatment response observed. Hematological toxicity (mostly thrombocytopenia and neutropenia) was the major DLT. Systemic exposure to NMS-1286937 increased with dose and was comparable between two cycles of treatment following oral administration of the drug. Conclusions This study successfully identified the MTD and DLTs for NMS-1286937 and characterized its safety profile.

The primary objective was to determine if multi-omic molecular profiling (MMP) informed selection of approved cancer treatments could change the clinical course of disease for patients with previously treated metastatic breast cancer (MBC) (i.e., produce a growth modulation index (GMI) ≥1.3). GMI was calculated as the ratio of progression free survival on MMP-selected therapy/time to progression on last prior treatment. To meet the primary objective at least 35 % of the subjects should demonstrate a GMI ≥1.3. Secondary endpoints included determining the response rate (according to RECIST 1.1), the percent of patients with non-progression at 4 months, and overall survival in patients whose therapy is selected by molecular profiling and proteomic analysis. Eligible patients had MBC, with ≥3 prior lines of therapy. A multi-omic based approach was performed incorporating multiplexed immunohistochemistry, c-DNA microarray, and phosphoprotein pathway activation mapping by reverse phase protein array. MMP was performed on fresh core biopsies; results were generated and sent to a Treatment Selection Committee (TSC) for review and treatment selection. Three sites enrolled 28 patients, of which 25 were evaluable. The median range of prior treatment was 7 (range 3-12). The MMP analysis and treatment recommendation were delivered within a median of 15.5 days from biopsy (range 12-23). The TSC selected MMP-rationalized treatment in 100 % (25/25) of cases. None of the MMP-based therapies were the same as what the clinician would have selected if the MMP had not been performed. GMI ≥1.3 was reported in 11/25 (44 %) patients. Partial responses were noted in 5/25 (20 %), stable disease in 8/25 (32 %) and 9/25 (36 %) had no progression at 4 months. This pilot study demonstrates the feasibility of finding possible treatments for patients with previously treated MBC using a multiplexed MMP-rationalized treatment recommendation. This MMP approach merits further investigation.

Background Increasing evidence suggests that AA (vitamin C) can decrease the growth of aggressive tumors, including Ras-mutant tumors, by inducing oxidative stress (Chen et al. PNAS 2008; Yun et al. Science 2015; Shoenfeld et al. Cancer Cell 2017). Despite the potential to produce toxic radicals, high dose AA has generally been well tolerated in animals and humans, including in combination with chemotherapy. The reason for the cancer-specific toxicity of AA is incompletely understood. One possibility is that AA targets cancer cells due to their having larger labile iron pools. Another is that cancer cells selectively take up the oxidized form of AA, dehydroascorbate, via the GLUT1 glucose transporter, causing glutathione (GSH) depletion, intracellular ascorbate accumulation, inactivation of glyceraldehyde 3-phosphate dehydrogenase, and energetic crisis selectively in glycolytic, GLUT1-expressing cancer cells. Based on the unmet medical need in MPC, its high frequency of Ras mutations, and prior work combing PP + C + G showing promising results in 24 pts with MPC with a response rate of 70.5%, median survival 16.4 mos, [J Clin Oncol 35, 2017 (suppl 4S; abstract 341)], here we are exploring the addition of AA to PP + C + G. Methods This Phase Ib/II pilot trial utilizes a 3 + 3 design for dose escalation of AA. Primary objective(s): Phase Ib - to determine the maximum tolerated dose (MTD) of AA with PP + C + G; phase II - to determine the preliminary efficacy (disease control rate of CR+ PR+ SD x 18 weeks) of the combination with AA at MTD in pts with MPC. Exploratory objectives include analysis of tumor texture on radiologic scans as an imaging biomarker for response, biologic, pathologic and outcome measures; correlation between peak plasma levels of AA and response to treatment; potential biomarkers in the tumor including tumor immune cell infiltration, stromal activation, stem cell enumeration; changes in numbers of circulating tumor stem cells and macrophage lineage changes. #NCT03410030 Eligibility criteria include stage IV MPC, no prior treatment for MPC, ECOG 0 -1, and measurable disease. Excluded are pts with a G6PD deficiency, history of renal oxalate stones, or need of frequent capillary blood glucose monitoring as AA causes false low readings. Planned sample size is up to 24 pts in Phase Ib, up to 21 pts in Phase II. Doses are PP 125 mg/m2, G 1000 mg/m2, C 25 mg/ m2 on days 1 & 8 of a 21 day cycle. AA infusions are given on days 1, 3, 8, 10, 15, and 17 of a 21-day cycle. The AA dose for phase II will be determined in the Phase 1b study based on tolerability of AA at 25, 37.5, 56.25 or 75 gm/m2. Tumor tissue analysis will be done on pre and optional post treatment tumor biopsies. Trial opened to enrollment 4/2018. As of 1/2019, 5 pts have been treated in the AA 25 gm/m2 cohort. Supported by SU2C, Cancer Research UK, Lustgarten Foundation & Destroy Pancreatic Cancer Citation Format: Gayle S. Jameson, Erkut H. Borazanci, Joshua D. Rabinowitz, David Propper, Karen Ansaldo, Denise J. Roe, Daniel D. Von Hoff. A Phase Ib/II trial of high dose ascorbic acid (AA) + paclitaxel protein bound (PP) + cisplatin (C) + gemcitabine (G) in patients (pts) with metastatic pancreatic cancer (MPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT163.

Background: Thrombocytopenia may be a concern in treating pancreatic ductal adenocarcinomas (PDAC). Due to anatomic position these tumors commonly cause narrowing or occlusion of the splenic vein which may lead to hypersplenism and thrombocytopenia due to sequestration. PDAC patients with thrombocytopenia have limited options for treatment. Partial splenic embolization (PSE) is a procedure developed as an alternative to splenectomy in individuals with hypersplenism. The purpose of our study was to review outcomes of PSE on thrombocytopenia in stage III and IV PDAC patients. Methods: From November 2015 through January 2018, we conducted a retrospective chart analysis of 8 patients with stage III or stage IV pancreatic cancer who had undergone PSE. The primary objective of this retrospective study was to understand the utility of PSE in treating thrombocytopenia in pancreatic cancer patients by the effect on the individual’s platelet count and the subsequent exposure to chemotherapy treatment. Specific demographic data points were recorded including date of diagnosis, stage, location of primary origin, and site of metastasis. Other data including hospital days post-embolization, post-embolization syndrome (PES), days to return of chemotherapy, survival, and pre/post platelet counts at designated intervals were reviewed. Results: Seven-eighths patients were diagnosed with stage IV pancreatic adenocarcinoma with the pancreatic head being the most common primary site (50%). Most common site of metastasis was liver. PES was found in 5/8 patients with the average number of hospital days after the procedure 1.38 (SD =1.06). Mean platelet count pre-splenic embolization was 93.00 (SD =12.59). One-week post-embolization mean platelet count was 147.00 (SD =69.60). Four-week ( χ =183.60, SD =64.93), six-week ( χ =148.40, SD =40.58), and three-month ( χ =161.00, SD =79.07) intervals were used to further assess platelet change. The results of the ANOVA were significant, F (4) =3.65, P=0.027, =0.48. Post-hoc analyses revealed significant differences between one-week and four-week post-embolization (P=0.008). Time to restarting chemotherapy ranged from 1 to 129 days with an average day to restarting chemotherapy of 24.12 (SD =42.70). The median overall survival was 7.22 months. Conclusions: In considering our study’s small sample size, PSE should be considered a safe approach in managing thrombocytopenia long-term in stage III or stage IV PDAC patients. PSE may allow for further chemotherapy to improve overall survival.

TPS473 Background: The Axl pathway coordinately mediates immune evasion and drug resistance in pancreatic cancer. Systemic Axl inhibition can enhance the efficacy of cancer therapy by blocking tumor cell proliferation, survival and drug resistance associated with epithelial-mesenchymal transition (EMT), and targeting innate immune suppression in the tumor microenvironment. Bemcentinib (BGB324) is a first in class, selective oral inhibitor of Axl. Our group has shown that bemcentinib therapy, in combination with gemcitabine, improved survival in multiple preclinical models of pancreatic cancer. Methods: This is a multicenter, randomized, phase 1b/2 clinical trial of nab-paclitaxel/gemcitabine/cisplatin with or without bemcentinib. Patients with metastatic pancreatic cancer, good performance status and preserved liver, kidney and hematologic function are eligible. The treatment schedule is as follows: Bemcentinib 100 or 200 mg daily, nab-paclitaxel 125 mg/m2, gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 intravenously on D1, 8 every 21 days. 3 -12 patients will be recruited in part 1 following a modified 3+3 dose finding scheme. Part 2 of the study is a 1:1 randomized phase 2 design enrolling 62 patients. The primary objective is to determine complete response rate. Secondary end points are overall response rate, PFS and adverse events. A parallel biomarker study will accompany the trial analyzing blood and tissue samples to determine the effect of chemotherapy and bemcentinib on 1) Axl pathway activity in tumor tissue, 2) changes in immune landscape including upregulation of immune cytokines, and immune cell infiltration into the tumor, 3) apoptosis and decreased proliferation of tumor and 4) to identify predictive biomarkers of response. Clinical trial information: NCT03649321.

Purpose: This study was designed to establish the maximum tolerated dose (MTD) and to evaluate tolerability, pharmacokinetics, and antitumor activity of etirinotecan pegol. Experimental Design: Patients with refractory solid malignancies were enrolled and assigned to escalating-dose cohorts. Patients received 1 infusion of etirinotecan pegol weekly 3 times every 4 weeks (w × 3q4w), or every 14 days (q14d), or every 21 days (q21d), with MTD as the primary end point using a standard 3 + 3 design. Results: Seventy-six patients were entered onto 3 dosing schedules (58–245 mg/m2). The MTD was 115 mg/m2 for the w × 3q4w schedule and 145 mg/m2 for both the q14d and q21d schedules. Most adverse events related to study drug were gastrointestinal disorders and were more frequent at higher doses of etirinotecan pegol. Late onset diarrhea was observed in some patients, the frequency of which generally correlated with dose density. Cholinergic diarrhea commonly seen with irinotecan treatment did not occur in patients treated with etirinotecan pegol. Etirinotecan pegol administration resulted in sustained and controlled systemic exposure to SN-38, which had a mean half-life of approximately 50 days. Overall, the pharmacokinetics of etirinotecan pegol are predictable and do not require complex dosing adjustments. Confirmed partial responses were observed in 8 patients with breast, colon, lung (small and squamous cell), bladder, cervical, and neuroendocrine cancer. Conclusion: Etirinotecan pegol showed substantial antitumor activity in patients with various solid tumors and a somewhat different safety profile compared with the irinotecan historical profile. The MTD recommended for phase II clinical trials is 145 mg/m2 q14d or q21d. Clin Cancer Res; 19(1); 268–78. ©2012 AACR.

A retrospective analysis of 130 patients was conducted in a Phase I oncology clinic to assess the effect of QTc formula selection on clinical trial eligibility. QTc values were calculated from screening electrocardiograms using 7 formulae (Bazett, Fridericia, Framingham, Hodges, Mayeda, Van de Water and Wohlfart). QTc values > 470 ms for females and > 450 ms for males were used to define prolongation. Concomitant medication potential for QTc prolongation was determined using a public database (AzCert). Ineligibility rates ranged from 3.1 % to 17.7 % (Framingham: 3.1 %, Van de Water: 3.1 %, Hodges: 3.1 %, Wohlfart: 3.1 %, Fridericia: 3.9 %, Bazett: 10.8 % and Mayeda: 17.7 %). A consistent ineligibility rate was achieved by using formulae-specific thresholds. Fifty one percent of patients were taking concomitant medications with QTc prolongation potential. The proportion of concomitant medications with the potential to prolong QTc was 11.57 % (96 of 830). Uniform criteria and guidelines for selection of QTc formulae need to be developed. Formulae-specific QTc thresholds also need to be specified.

Objective: LY2603618, a selective inhibitor of checkpoint kinase 1 (CHK1) and key regulator of the DNA damage checkpoint, may enhance the effects of antimetabolites. This phase I study defined the recommended phase II dose of LY2603618 combined with gemcitabine. Patients and Methods: Patients with advanced/metastatic disease were administered doses of LY2603618 (70-250 mg/m2 or flat-fixed doses of 200 or 230 mg) after gemcitabine (1,000 mg/m2). Safety and pharmacokinetics (PK) were assessed. Results: Among the 50 patients enrolled, frequent adverse events possibly related to study drug treatment included fatigue (44%), decreased platelets (42%), decreased neutrophils (32%), nausea (26%), and decreased hemoglobin (20%). Systemic exposure of LY2603618 increased dose dependently, while clearance was relatively dose independent. The mean LY2603618 half-life varied; however, the durations were still suitable for maintaining human exposures while minimizing accumulation. LY2603618 PK were not altered by gemcitabine administration. Plasma exposures that correlate with the maximal pharmacodynamic effect in nonclinical models were achieved for all doses. One patient with non-small cell lung cancer carcinoma achieved a partial response; 22 patients had stable disease. Conclusions: The maximum tolerated dose of LY2603618 combined with gemcitabine was 200 mg/m2, but a fixed LY2603618 dose of 230 mg combined with gemcitabine was selected as the recommended phase II dose.

Objective Certain eligibility criteria for Phase 1 cancer clinical trials may impede successful patient enrollment onto a study. We evaluated patient-specific or study-specific reasons for screen failures on Phase 1 oncology clinical trials and discuss factors which may inhibit subject enrollment. Methods Thirty-eight Phase 1 clinical trials for solid tumors meeting eligibility criteria and opened for enrollment between February 2006 and February 2011 at one oncology Phase 1 program were examined. Categorical reasons for screen failures and patients’ demographics were examined and compared to characteristics of patients that successfully enrolled on a Phase 1 trial. Results There were a total of 583 successful Phase 1 enrollment and dose administration events out of 773 Phase 1 consent events (75.4 % dose success rate). The three most common reasons for screen failure were: out of protocol-specified range for chemistry, development of an interval medical issue that precluded proceeding with study participation, and subject declining participation after signing consent. Living further away from the Phase 1 program and receipt of fewer prior lines of systemic chemotherapy were significantly associated with increased screen failures. Conclusion Screen failures for Phase 1 studies are not uncommon (24.6 %). When a protocol required tumor or host analyte is not required, most screen failures are due to out of protocol-specified range for chemistry or the development of an interval medical issue. Screen failure rates were increased when patients had longer travel distances and fewer prior lines of systemic chemotherapy.

Concomitant medication (CM) use may result in Phase I cancer clinical trial ineligibility due to concern for potential CM-investigational drug interactions or alteration of investigational drug absorption. Few studies have examined the impact of CM use on trial eligibility. Methods: We reviewed records of 274 patients on Phase I trials at a single academic institution. Demographics, CM identities and classes, CM discontinuation, reasons, and incidence of CM substitution were recorded. CM-investigational drug cytochrome P450 (CYP) enzyme interactions were documented. Statistical analysis was performed using descriptive statistics. Results: 273 of 274 patients (99.6%, 95% confidence interval [CI] 98.9-100%) took CM, with a median of 8 CM per patient (range 0 - 42). CM discontinuation occurred in 67 cases (25%, 95% CI 19-30%). The most common CM classes discontinued were herbal (17 cases, 25%, 95% CI 16-37%) and proton pump inhibitors (15 cases, 22%, 95% CI 12-32%). CM discontinuation reasons were: protocol prohibition (32 cases, 48%, 95% CI 36-60%); potential CM-investigational drug interaction (25 cases, 37%, 95% CI 26-49%); other (10 cases, 15%, 95% CI 6-23%). A potential CM-investigational drug CYP interaction was noted in 122 cases (45%, 95% CI 39-50%). CM potentially weakly decreased investigational drug metabolism in 52 cases (43%, 95% CI 34-51%), and potentially strongly decreased investigational drug metabolism in 17 cases (14%, 95% CI 8-20%). Investigational drug potentially weakly decreased CM metabolism in 39 cases (32%, 95% CI 24-40%), and potentially strongly decreased CM metabolism in 28 cases (23%, 95% CI 15-30%). CM substitution occurred in 36/67 cases (54%, 95% CI 41-66%) where CM were discontinued to allow for eventual participation in clinical trials. Overall in 2 cases (0.7%, 95% CI 0.1-2.6%), patients were protocol ineligible because CM could not be discontinued or substituted. Conclusions: This study highlights the high prevalence of concomitant medication use among cancer patients enrolled in phase I clinical trials. Most patients did meet trial eligibility criteria with careful substitution and discontinuation of CM. The most common reason for discontinuation of CM was protocol prohibition. The most common medications discontinued were herbal, proton pump inhibitors, selective serotonin reuptake inhibitor anti-depressants, and non-steroidal anti-inflammatory drugs.

Background: There is often a finite progression-free interval of time between one systemic therapy and the next when treating patients with advanced cancer. While it appears that progression-free survival (PFS) between systemic therapies tends to get shorter for a number of factors, there has not been a formal evaluation of diverse tumor types in an advanced cancer population treated with commercially-available systemic therapies. Methods: In an attempt to clarify the relationship between PFS between subsequent systemic therapies, we analyzed the records of 165 advanced cancer patients coming to our clinic for consideration for participation in six different phase I clinical trials requiring detailed and extensive past medical treatment history documentation. Results: There were 77 men and 65 women meeting inclusion criteria with a median age at diagnosis of 55.3 years (range 9.4-81.6). The most common cancer types were colorectal (13.9%), other gastrointestinal (11.8%), prostate (11.8%). A median of 3 (range 1-11) systemic therapies were received prior to phase I evaluation. There was a significant decrease in PFS in systemic therapy for advanced disease from treatment 1 to treatment 2 to treatment 3 (p = 0.002), as well as, from treatment 1 through treatment 5 (p < 0.001). Conclusions: In an advanced cancer population of diverse tumor types, we observe a statistically significant decrease in PFS with each successive standard therapy. Identification of new therapies that reverse this trend of decreasing PFS may lead to improved clinical outcomes.

TPS4154Background: Pancreatic cancer remains a deadly disease and despite advances in chemotherapy treatment, survival for most patients is still less than one year. Refractory pancreatic cancer ha...

358 Background: Effective therapy for the treatment of PDAC remains one of the greatest unmet oncology clinical needs. The addition of C to G and AP has shown promising clinical data in a previously reported study [J Clin Oncol 35, 2017 (suppl 4S; abstract 341)]. In preclinical work, vitamin D (Vit D) analog therapy decreases myeloid derived suppressor cells and regulatory T cells, turning PDAC into a more immune-friendly microenvironment. This trial combines AP/C/G with Vit D analog P and the anti-PD-1 antibody N as a combination therapy for patients with previously untreated metastatic PDAC. This trial evaluates the efficacy and safety of NAPPCG in that patient population (NCT02754726). Methods: Eligibility criteria include Stage IV PDAC, no prior chemotherapy for systemic disease, KPS ≥ 70, and measurable disease. Doses are AP 125 mg/m2 undiluted, G 1000 mg/m2 in 250 ml of normal saline (NS), each infused over 30 minutes with C 25 mg/ m2 in 500 ml of NS infused over 60 minutes on days 1, 8, 22, and 29 of a 42-day cycle. N is given at a fixed dose of 240 mg as a 60 minute infusion on days 1, 15, and 29. P is given at a fixed dose of 25 µg IV twice weekly. Primary objective is to determine the efficacy of the combination for patients with previously untreated metastatic PDAC through determining CR, ORR, PFS, and OS. The secondary objective is to evaluate safety in patients with previously untreated metastatic PDAC. Results: Trial was initiated May 2016 and10 patients have been enrolled in the initial phase of the study and are evaluable (baseline and ≥1 follow up CT scan). Most common drug-related grade (Gr) 3-4 adverse events (AE’s), n = 10, are thrombocytopenia 100% (gr 3 = 50%, gr 4 = 50%) with no serious bleeding events, anemia 50% (gr 3 = 50%, gr 4 = 0%), and colitis 20% (gr 3 = 20%, gr 4 = 0%). By RECIST 1.1 criteria, the best response is 8 PR and 2 SD, yielding an 80% ORR. Median PFS is 8.2 months. Median OS has not been reached. Conclusions: Although a small study, the high response rate is encouraging. This regimen is being expanded to 25 patients with plans to include exploratory inflammatory biomarkers. Clinical trial information: NCT02754726.

Marantic endocarditis, otherwise known as nonbacterial thrombotic endocarditis (NBTE), is a well-documented phenomenon due to hypercoagulability from an underlying cause. It has been associated with a variety of inflammatory states including malignancy. Surprisingly, although hypercoagulability is often seen in patients with pancreatic cancer, marantic endocarditis has rarely been reported antemortem in this population. We report three cases of marantic endocarditis in patients with advanced pancreatic cancer. In two instances, the patients’ neurological symptoms preceded the diagnosis of advanced pancreatic cancer. Health care professionals should be alert to the possibility of marantic endocarditis in any patient with cancer, especially pancreatic cancer, who presents with symptoms of neurological dysfunction or an arterial thrombotic event. Prompt diagnosis and treatment with heparin, unfractionated or low molecular weight, may prevent catastrophic CNS events and decrease morbidity in patients with pancreatic cancer and other malignancies.

Meigs’ syndrome is characterized by nonmalignant ascites and pleural effusions in women with ovarian fibromas, thecomas, granulosa cell tumors, or Brenner’s tumors [1]. Importantly, both the ascites and pleural effusions spontaneously resolve after removal of the ovarian tumor. Pseudo-Meigs’ syndrome refers to the same clinical presentation and course in the setting of other ovarian tumors. Pseudo-Meigs’ syndrome is rare and most often associated with struma ovarii or uterine tumors such as leiomyomas; however, there are reports associated with ovarian metastases, including gastrointestinal malignancies [2]. Here, we report the first case of pseudo-Meigs’ syndrome secondary to metastatic pancreatic adenocarcinoma. In addition, the reported patient presented during pregnancy. Pseudo-Meigs’ has been described during pregnancy, though this is the first case reported from ovarian metastases.

4127 Background: In the NAPOLI-1 study, nal-IRI+5-FU/LV significantly increased median OS vs. 5-FU/LV control (6.1 vs. 4.2 mo; unstratified HR = 0.67 [0.49–0.92]; p = .012). This is a subgroup analysis by prior lines of mtx. Methods: Study methodology has been published (Wang-Gillam; Lancet 2016). This exploratory subgroup analysis compares outcomes in pts with 0–1 vs. ≥2 prior mtx lines, based on primary survival analysis data (cut-off February 2014) of the ITT population. Results: OS, PFS and CA19-9 response rates in pts with 0–1 (65.8% of pts) or ≥2 (34.2%) prior mtx lines are shown (see Table). Median OS for nal-IRI+5-FU/LV improved vs. 5-FU/LV by 2.1 mo to 6.2 mo (HR = 0.66; p = .03) in pts with 0–1 prior mtx lines and by 1.1 mo to 5.4 mo (HR = 0.68; p = .18) in pts with ≥2 prior mtx lines. The safety profile was similar between subgroups with nal-IRI+5-FU/LV (≥grade 3 drug-related AEs: 43 [55%] with 0–1 and 20 [51%] with ≥2 prior mtx lines). Conclusions: This post-hoc subgroup analysis shows significant increases for nal-IRI+5-FU/LV over 5-FU/LV in OS, PFS and CA19-9 response in pts with 0–1 prior mtx lines. Median OS benefit was less prominent in later lines, but conclusions are restricted by limited pt numbers. Clinical trial information: NCT01494506. [Table: see text]

359 Background: GA, FOLFIRINOX and FOLFIRI are standard chemotherapy (CTX) regimens for mPC.The optimal introduction of these regimens following GA is not known. This phase II study evaluated 2 different approaches to this question. Methods: Eligibility criteria included 1) untreated mPC, 2) ECOG PS 0/1, 3) organ function adequate for Rx. Patients (pts) were treated according to one of 2 methods following GA given per standard dose/schedule: FOLFIRINOX (bolus 5-FU omitted) for up to 12 cycles at 24 weeks or at time of disease progression (S); or GA alternating with FOLFIRI q8 weeks up to 48 weeks total Rx (A). Results: 54 evaluable pts (28S, 26A) were enrolled . Pt characteristics included median age 65, M/F 48/52% , liver involvement 89%. 17/53 pts (31%) did not achieve disease control at 8 weeks (8 toxicity/complications , 6 disease progression, 3 declined further protocol therapy). Of the remaining 37 pts, 24/13 were treated with S/A regimens, respectively. Grade ≥ 3 treatment toxicities reported while on study with frequency ≥ 10% included anemia 21%, neutropenia 43%, thrombocytopenia 15%, and fatigue 22%. Grade ≥ 3 neuropathy occurred in 8% of pts. For all 54 pts using RECIST 1.0, CR/PR/SD/DC was 2 (4%)/20 (37%)/19 (35%)/41(76%). Ca19.9 response ≥ 90% was seen in 20/37 (54%). For all pts, median OS was 12.3 months ( 95% CI 8.6-14.5 mo); 12 and 24 mo OS was 51% and 11%, respectively. For the 37 pts with DC on GA at 8 weeks (calculated from start Rx) median OS was 13.5 mo (95% CI 10.7-15.4 mo); 12 and 24 mo OS was 55% and 16% , respectively. No statistically significant differences were seen between S and A with respect to toxicity, response or survival. Conclusions: 1) As opposed to introduction of 5FU-based CTX at the time of disease progression/prohibitive toxicity, introduction prior to that time may be at least comparable regarding both toxicity and OS. 2) This approach may further enhance OS in pts who achieve DC on GA at 8 weeks. 3) Neither S nor A method of 5FU-based CTX introduction following GA was clearly superior in this study. 4) How best to combine 5FU-based combination CTX following GA in mPC merits further study. Supported by the Seena Magowitz Foundation.

TPS511 Background: Despite decades of basic and clinical research, effective therapy for the treatment of patients with pancreatic ductal adenocarcinoma (PDAC) remains one of the greatest unmet clinical needs in oncology today. Albumin-bound paclitaxel (AP) and gemcitabine (G) reported on an improvement in overall survival in metastatic (m) PDAC [NEJM 2013; 369:1691-1703]. The addition of cisplatin (C) has shown promising clinical data in previously reported studies [Cancer Res 2015; 75(15 Suppl):Abstract nr LB-003]. Through further preclinical work, vitamin D analog therapy decreases myeloid derived suppressor cell (MDSC) and regulating T cells (Tregs) thus turning PDAC into a more immune friendly microenvironment. This trial combines AP/C/G with the vitamin D analog paricalcitol (P) and the antibody-PD-1 drug Nivolumab (N) as a combination therapy for individuals with previously untreated metastatic PDAC. This trial evaluates the efficacy and safety of NAPPCG in patients in that population (NCT02754726). Methods: Key eligibility criteria include Stage IV PDAC, no prior chemotherapy for systemic disease, KPS ≥ 70; life expectancy ≥ 12 weeks and measurable disease. Key exclusion criteria include prior PD-1 or PD-L1 therapy. Doses are AP 125 mg/m2 undiluted, G 1000 mg/m2 in 500 ml of normal saline (NS), each infused over 30 minutes with C 25mg/ m2 in 500 ml of NS infused over 60 minutes on days 1, 8, 22, and 29 of a 42 day cycle. N is given at a fixed dose of 240 mg as a 60 minute infusion on days 1, 15, and 29. P is given at a fixed dose of 25 µg IV on days 1,4,8,12,15,22,26,29,32,36,and 39. Primary objective is to determine the efficacy of the combination NAPPCG for patients with previously untreated metastatic PDAC through determining CR, ORR, PFS, and OS. The secondary objective is to evaluate the safety of NAPPCG in patients with previously untreated metastatic PDAC. The study initiated accrual in April of 2016. If 4 of the first 10 patients are determined to have a PR the trial will expand to a total of 25 patients. Clinical trial information: NCT02754726.

TPS502 Background: The microbiome is a burgeoning field involving the study of the microbial flora in humans and its effect on health. The human microbiome is altered by several environmental factors and may play a great role in inflammation and possibly in the development in several malignancies including pancreatic cancer. The purpose of this study is to characterize the skin microbiomes on the forehead and cheek of people with pancreas cancer compared to people with other forms of cancer and people without cancer by utilizing the ProdermIQ skin profiling platform. Methods: This is a prospective, open-label, pilot study. Sampling will be done as one time collection after informed consent through a skin swab on the forehead and one on the cheek. Subjects with a diagnosis of pancreatic adenocarcinoma, subjects with a diagnosis of malignancy other than pancreatic adenocarcinoma, and subjects without a diagnosis of malignancy will be enrolled for three separate arms of the study. Each study arm is composed of 25 individuals for a total of 75. Key inclusion criteria include subjects at least 18 years of age and a histologically confirmed diagnosis of pancreatic adenocarcinoma in the pancreas arm; a histological confirmed diagnosis of a malignancy other than pancreatic cancer in the other cancer arm; and individuals without cancer. Individuals with a rash or skin disorder will be excluded from the study. Once all swabs are collected they will be batch tested through next generation sequencing to characterize the skin microbiomes. A comprehensive comparison will be constructed of the profiles of each study group.

TPS518 Background: CIPN is an unsolved, common problem for cancer pts. CIPN greatly affects quality of life and may impact quantity of life due to dose reductions and discontinuation of beneficial therapy. No generally accepted evidence-based prevention strategies for CIPN exist. In the discipline of hand therapy (HT), there are effective science-based interventions to treat peripheral neuropathies due to injury and disease. These interventions have not been explored in patients with CIPN. Methods: Study objective is to determine if an IHT intervention based on concepts of neuroplasticity can prevent or delay time to onset of CIPN of the hands as measured by Patient Reported Outcomes & Criteria for Adverse Events, version 4 (CTCAE 4.0), compared to a TOT intervention. Eligible pts have pancreatic cancer and receive nab-paclitaxel + gemcitabine containing combinations; have no prior evidence of peripheral neuropathy (PN) of the hands and are not taking duloxetine or gabapentin. Randomization is 1:1. Patient instructions on the blinded IHT or TOT activities are done by an Occupational Therapist prior to start of CTX, then reinforced at multiple follow-up sessions. Periodic assessments include standardized hand sensibility testing: QuickDASH, upper extremity provocative testing, TEN Test; plus pt reporting of CIPN onset, CTCAE-4, physical examination of peripheral sensory/motor neurologic assessment of the hands, Karnofsky Performance Status, and pain visual analogue scale. Participation in the study with a daily home program continues until onset of CIPN of the hands or if no CIPN then through completion of an 84 day schedule of chemotherapy. The number and proportion of patients without CIPN of the hands at the end of 84 days of CTX will be summarized for both intervention groups. For an 80% powered design with a medium effect size, 40 evaluable pts are needed (95% CI, alpha .05). Planned enrollment is up to 50 pts allowing for pt attrition. Study opened to enrollment 8/2016.

341 Background: Genomes of metastatic pancreatic cancers frequently contain intrachromosomal aberrations indicating DNA repair abnormalities associated with sensitivity to DNA damaging agents such as the platinums. Cisplatin was added to a nab-paclitaxel + gemcitabine regimen, which has been determined to improve survival over gemcitabine alone (NEJM 2013; 369:1691-1703). The objectives are to determine the efficacy and safety of nab-paclitaxel and gemcitabine plus cisplatin in patients with Stage IV pancreatic cancer. Methods: Eligibility criteria included Stage IV adenocarcinoma of the pancreas, no prior chemotherapy for systemic disease, KPS ≥ 70; life expectancy ≥ 12 weeks and measurable disease. Doses are nab-paclitaxel 125 mg/m2 undiluted, gemcitabine 1000 mg/m2 in 500 ml of normal saline (NS), each infused over 30 minutes on days 1 and 8 of a 21 day cycle, along with 3 different dose levels of cisplatin (25, 37.5 or 50 mg/m2) in 500 ml of NS infused over 60 minutes, after the nab-paclitaxel infusion. Pre and post cisplatin hydration was given. The maximum tolerated dose and phase II dose of cisplatin is 25 mg/m2. Results: 25 pts were treated; 24 were evaluable (baseline and ≥ 1 follow up CT scan). The most common drug related grade (gr) 3 - 4 adverse events (AEs), n = 25, were thrombocytopenia 76% (gr 3 = 36%, gr 4 = 40%) with no serious bleeding events, anemia 32% (gr 3 = 32%, gr 4 = 0%), neutropenia 24% (gr 3 = 20%, gr 4 = 4%), infection 20% (gr 3 = 16%, gr 4 = 4%), and diarrhea 16% (gr 3 = 16%, gr 4 = 0%). Peripheral neuropathy ≥ gr 3 was seen in only 1 pt (gr 3 = 4%). Grade 5 AEs were infection (1), cardiac arrest (1), and stroke (1). Median time on therapy was 5.5 months, range (1 – 9.5). By RECIST 1.1 criteria, 2 pts had complete response (8.3%), 15 partial response (62.5%), 4 stable disease (16.7%), and 3 progressive disease (12.5%). Median overall survival to date as of 11/10/16 is 16.5 months. Conclusions: Although a small study, the high response rate and landmark evolving median survival are very encouraging. This regimen is being expanded in patients with stage IV pancreatic cancer, neoadjuvant and adjuvant settings. Clinical trial information: NCT01893801.

1037Background: There is an unmet need for rapid assays predictive of efficacy for specific chemotherapy agents. In particular, for those patients with metastatic disease that have progressed on pr...