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e21050 Background: Programmed death ligand-1 (PD-L1) expression is predictive of immunotherapy benefit. However, tissue PD-L1 protein immunohistochemical testing can be fraught with tissue acquisition and heterogeneity limitations. PD-L1 expression by RNA sequencing can be performed by both tissue and plasma with tissue PD-L1 protein correlations. What has not been well characterized is the correlation of plasma cell free circulating tumor RNA (cfRNA) PD-L1 and clinical outcomes with immunotherapy. Plasma cfRNA PD-L1 expression was evaluated and correlated with immunotherapy benefit in advanced non-small cell lung cancers (NSCLC). Methods: Patients with advanced NSCLC undergoing plasma next-generation sequencing including plasma cfRNA.PD-L1 testing in a Clinical Laboratory Improvement Amendments (CLIA) and College of American pathologists (CAP) accredited laboratory were retrospectively identified and evaluated at a single institution. Plasma PD-L1 positive patients underwent a de-identified chart abstraction to identify those patients with advanced NSCLC treated with front line immunotherapy regimens and those who received cytotoxic chemotherapy alone. Results: Sixteen patients with plasma PD-L1 expression treated with front-line immunotherapy regimens including single-agent immune checkpoint inhibitors, and combinatorial chemo-immune or chemo-immune-bevacizumab regimens were assessed for overall survival (OS). Eleven patients with plasma PD-L1 expression who received chemotherapy were used as a non-immunotherapy OS comparison. Median OS for the immunotherapy treated patients was thirteen months with a thirty percent three year landmark OS versus four months median OS and a ten percent three-year landmark OS for those treated with chemotherapy alone. Comparative log-rank test p-value 0.0091 and a hazard ratio of 0.36 (95%-CI 0.13-0.99). Conclusions: Plasma cfRNA PD-L1 expression is predictive of a statistically significant survival benefit from immunotherapy treatment compared to chemotherapy in the first line treatment of advanced NSCLC. The three year landmark OS of thirty percent parallels tissue PD-L1 directed immunotherapy-based treatment outcomes. The clinical utility of plasma cfRNA PD-L1 to overcome tissue acquisition and PD-L1 protein heterogeneity limitations and to study the dynamic nature of PD-L1 expression with non-immune cancer treatments and potential immunotherapy response monitoring are undergoing ongoing research.

e15083 Background: FN-1501, a potent inhibitor of receptor FMS-like tyrosine kinase 3 (FLT3) and CDK4/6, KIT, PDGFR, VEGFR2, ALK and RET tyrosine kinase proteins, has demonstrated significant in vivo anti-tumor activity in a broad range of solid tumor and leukemia xenograft models. FLT3 mutations have an established role as a therapeutic target in Acute Myeloid Leukemia (AML), where the gene plays a critical role in the growth, differentiation, and survival of hematopoietic cells. An open-label, Phase I/II study ( NCT03690154 ) is evaluating the safety and PK profile of FN-1501 as monotherapy in patients (pts) with advanced solid tumors and relapsed, refractory (R/R) AML. Methods: Pts received FN-1501 IV thrice weekly for 2 weeks followed by 1 week off treatment in 21-day cycles. Dose escalation follows a 3+3 design. Primary objectives include determination of maximum tolerated dose (MTD), safety, and recommended phase 2 dose (RP2D). Secondary objectives include pharmacokinetics (PK) and preliminary anti-tumor activity. Exploratory objectives include the relationship between pharmacogenetic mutations (e.g., FLT3, TP53, KRAS, NRAS), safety, efficacy and pharmacodynamic effects of FN-1501. Dose expansion at RP2D was designed to further explore safety and efficacy. Results: As of Dec 3, 2021 data cut-off (DCO), 47 pts with advanced solid tumors (N = 46) or AML (N = 1) were enrolled at doses ranging from 2.5 to 226 mg. The median age was 65 (range 30-92) with 57% female and 43% male. The median prior lines of treatment were 5 (range 1-12). Forty pts with median exposure of 9.5 cycles (range 1-18 cycles) were evaluable for dose limiting toxicity (DLT). Treatment-related adverse events (TRAEs) were reported in 64% of pts. The most common treatment-emergent adverse events (TEAEs) defined as those occurring in ≥ 20% of patients primarily consisted of reversible grade 1-2 fatigue (34%), nausea (32%) and diarrhea (26%). The most common grade ≥ 3 events occurring in ≥ 5% of pts consisted of diarrhea and hyponatremia. Dose escalation was discontinued due to DLTs of grade 3 thrombocytopenia (N = 1) and grade 3 infusion related reaction (N = 1) in 2 pts in the 226 mg dose group (2nd DLT reported after DCO). At the time of DCO, 33 pts were evaluable for disease response showing 1 with partial response (PR) (47% target lesion shrinkage), 15 with stable disease (SD) and 17 with progression of disease (PD). The PR lasted > 4 months (mts) in a patient with endometrial carcinoma (ca) at the 40 mg dose level. The longest treatment exposures were recorded in 6 pts with SD of 2.6 to > 12 mts (thymoma [1]; ovarian ca [2]; renal cell ca [1]; laryngeal ca [1] and intestinal adeno ca [1]) at doses ranging from 15 mg to 170 mg. Conclusions: FN-1501 IV has shown reasonable safety, tolerability, and preliminary activity against solid tumors up to 170 mg. Dose escalation was terminated based on 2 DLTs occurring at the 226 mg dose level. Clinical trial information: NCT03690154.

409 Background: SBRT is being increasingly utilized for control of primary as well as metastatic liver tumors. Early reports for central hepatobiliary toxicity have been published. We reviewed all liver SBRT cases treated at our institution for incidence of central hepatobiliary toxicity and evaluated the relation with planned dosimetry to define predictors to limit toxicity for future patients. Methods: 43 consecutive patients treated with liver SBRT between 3/2017 to 7/2021 were included in the study. 40 patients were eligible for analysis as 3 were lost to followup. These included- 31 Hepatocellular Carcinoma (HCC), 6 cholangiocarcinoma (CC) and 3 metastatic lesions. They received 35-50 Gy in 3-5 fractions utilizing VMAT for radiation planning and treated on Truebeam in Bodyfix immobilization and 4D scans utilized to create ITV for motion management along with MRI fusion for target delineation. All patients were prospectively planned with CBD spared to max dose 3 mnth follow up were evaluated for subacute and chronic toxicity. Toxicity grades were grade 4- 3 patients (7.5%), grade 3 -5 patients (12.5%), < grade 2- 32 patients (80%). Local control rates at primary sites of disease were 34 patients (85%). 35 patients with >3 mnth follow up were evaluated for subacute and chronic toxicity. Median PTV volume was 241cc (21.5-1087.5cc). 6 (15%) patients had portal vein thrombosis. Median dose was 40 Gy in 5 fractions. There was no correlation between Dmax for CBD, PV and cHBT with toxicity. cHBT V30 and V40 showed trends towards statistical significance V30 and V40 for cHBT showed a trend towards statistical correlation (coeff 0.63) but no statistically significant dosimetric association. All patients that developed grade 4 toxicity had portal vein thrombosis or lesion involving the hilum. Conclusions: Central hepatobiliary toxicity is seen in 7.5% patients with Liver SBRT. The risk is higher in patients with portal vein thrombosis. Moderate doses 30-40 Gy seem to be a better predictor of toxicity and should be limited during planning especially in patients with portal vein thrombosis. This finding confirms the reported explant data from pathology reviews in the published literature. This data needs to be validated in a larger prospectively evaluated sample.

277 Background: Pembrolizumab monotherapy, whilst not standard of care, has demonstrated efficacy in clear cell renal cell carcinoma (ccRCC). The first-line KEYNOTE-427 study demonstrated an overall response rate (ORR) of 34%, and a median progression-free survival (PFS) of 7.1 mo (McDermott D et al. J Clin Oncol 2020; 38:S15; 5069-5069). Stereotactic ablative body radiotherapy (SABR) is an option for oligometastatic ccRCC, but patients often develop distant progression or relapse within irradiated sites. The RAPPORT study (NCT02855203) was a multi-institutional single arm, phase I/II study evaluating safety and efficacy of SABR and pembrolizumab. Methods: Patients with up to 2 lines of prior systemic therapy with 1-5 oligometastases from ccRCC were eligible. A single fraction of 20Gy SABR to all metastatic sites was given (or 10 fractions of 3 Gy of conventional radiotherapy [CRT] if SABR was not feasible), followed by pembrolizumab 200mg administered Q3W for 8 cycles. The primary objective was safety (CTCAEv4.03), with secondary key objectives of efficacy (RECIST1.1) by disease control rate (DCR), defined as complete response (CR), partial response (PR) or stable disease for at least 6 months, ORR, PFS and overall survival (OS). Results: Thirty patients were enrolled and received protocol treatment. The median follow-up was was 2.3 years. The median age was 62 (range 47-80) years, 23 patients (77%) were male. Twenty-three patients (77%) were treatment naïve, 1 patient (3%) had a prior interleukin-2 therapy and 6 patients (20%) had a prior tyrosine kinase inhibitor. Nine patients (30%) had prior metastasectomy. Eighty-three oligometastases were treated (median of 3 per patient), of which 64 (77%) received SABR, and 19 (23%) received CRT. There were 8 adrenal, 11 bone, 43 lung, 12 lymph node and 9 soft tissue metastases irradiated. Four patients (13% [95%CI: 4-31%]) had one or more grade 3 treatment-related AE: Pneumonitis (n=2), dyspnoea (n=1) and elevated ALP/ALT (n=1). There were no grade 4 or 5 AEs. All eight cycles of pembrolizumab were completed by 24 (80%) patients. DCR was 83% (95%CI: 65-94%). ORRs are tabulated below. Median PFS was 15.6 mo. Estimated 1 and 2-year OS was 90% (95%CI: 72-97%) and 74% (95%CI: 53-87%), respectively, while PFS was 60% (95%CI: 40-75%) and 45% (95%CI: 27-62%), respectively. Freedom from local progression at 2-years was 92% (95%CI: 80-97%). Conclusions: The combination of SABR and pembrolizumab in oligometastatic renal cell carcinoma is well tolerated with excellent local control. Durable responses and encouraging PFS were observed with this approach, which warrants further investigation. Clinical trial information: NCT02855203 . [Table: see text]

TPS180 Background: 177Lu‐PSMA-617 (Lu-PSMA) is a radiolabeled small-molecule that binds with high affinity to PSMA enabling highly targeted delivery of beta radiation to prostate cancer cells. In metastatic castration-resistant prostate cancer, Lu-PSMA showed superior activity to Cabazitaxel in the TheraP trial. Although androgen deprivation therapy (ADT) + Docetaxel is a standard of care for de novo high-volume mHNPC, outcomes remain sub-optimal for many patients. We hypothesize that Lu-PSMA prior to docetaxel will achieve a higher undetectable PSA rate at 12 months compared to docetaxel alone in men with newly-diagnosed high-volume mHNPC. Methods: UpFrontPSMA is an open label, randomized, stratified, 2-arm, multi-center, phase 2 clinical trial recruiting 140 patients at 11 Australian centers. Key eligibility criteria include histological diagnosis of prostate cancer within 12 weeks, PSA > 10ng/ml at diagnosis, < 4 weeks on ADT, and high-volume (≥ 4 bone metastases with ≥ 1 outside the axial skeleton, and/or visceral metastases), PSMA-avid disease on 68Ga-PSMA-11 PET/CT with no major discordance on 18FDG-PET/CT. Patients will be randomized 1:1 to the experimental arm (Lu-PSMA 7.5 GBq q6w x 2 cycles followed 6 weeks later by docetaxel 75mg/m2 q3w x 6 cycles), or standard-of-care Arm (docetaxel alone). All patients will receive continuous ADT. Assessments will be done every 3 weeks during study treatment, and then every 6-12 weeks until unequivocal disease progression. CT and whole body bone scan will be performed at baseline and every 12 weeks, 68Ga-PSMA-11 PET/CT at baseline and 12 weeks, and 18FDG-PET/CT at baseline and 12 weeks (if applicable). Correlative samples will include optional tumour tissue (baseline and disease progression), and serial plasma/whole blood collection. The primary endpoint is undetectable PSA (≤ 0.2 ng/ml) at 12 months. Secondary endpoints are safety, time to castration resistance, PSA-progression-free-survival (PSA-PFS), radiographic PFS, radiographic response rates, early PSMA-PET response rates, quality of life and overall survival. Exploratory endpoints are prognostic and predictive value of PET-derived parameters and of biomarkers identified in plasma/whole blood/tumour tissue. The study will have 85% power to reject the null hypothesis if the true 12 month undetectable PSA rate in the experimental Arm is 50%. The power calculation assumes no more than 10 patients (7%) of the 140 patients will be unevaluable or lost to follow-up in 1 year, 5% alpha and two-sided test for proportions. As of October 13, 2020, accrual stands at 4. UpFrontPSMA is an investigator-led, academic trial sponsored by Peter MacCallum Cancer Centre in collaboration with ANZUP Cancer Trials Group with study coordination provided by the Centre for Biostatistics and Clinical Trials (BaCT) Clinical trial information: NCT04343885.

e21564 Background: Tissue biomarkers like programmed cell death ligand-1 (PD-L1), microsatellite instability (MSI) and high tumor mutational burden (TMB) are surrogates in identifying patients with non-small cell lung cancer (NSCLC) for treatment with immune checkpoint blockade (ICB) therapy. Although tissue biopsy is widely used for identifying the tumor biology, the invasive nature as well as insufficiency of tissue biopsy specimens limits its application. Liquid biopsy is a minimally invasive procedure and has gained interest in recent times for profiling cancer. We sought to study the correlation in the molecular tumor profile specifically PD-L1, MSI and TMB markers between the tissue and liquid biopsies. Methods: We conducted a retrospective review of patients with Stage 3, 4 and recurrent NSCLC that underwent tissue next generation sequencing (NGS) using Caris life sciences and liquid biopsy using Circulogene molecular diagnostics from January 2018 to December 2019 at East Carolina University. A total of 524 patients were reviewed out of which 199 patients had both liquid and tissue NGS performed at the time of initial diagnosis. TMB high was defined as greater than 10 mut/Mb whereas TMB low as less than or equal to 10 mut/Mb. PD-L1 was divided into negative (0%), 1-49% and ≥50%. The blood MSI was classified as positive or negative. We used frequency table, logistic regression and Pearson bivariate correlation for statistical analysis using SPSS platform. Results: The study cohort had 60% (n = 119) male and 40% (n = 80) female patients of which 53% (n = 105) were Caucasians and 45% (n = 89) were African Americans. A total of 87 patients (44%) had negative tissue PD-L1, 59 patients (30%) had tissue PD-L1 ≥ 50%. A linear correlation was seen between negative tissue PD-L1 and negative blood PD-L1 in 92% of patients (n = 80). However, only 15.3% (n = 9) had correlating tissue PD-L1 and blood PD-L1 ≥ 50%, p = 0.024. The negative blood MSI correlated to low tissue TMB in 83% ( n = 60) whereas positive blood MSI correlated to high tissue TMB in 25% (n = 19), p = 0.023. Conclusions: Our results indicate a linear correlation between tissue PD-L1 and blood PD-L1. Similarly, a linear correlation was seen between blood MSI and tissue TMB. Further studies are needed to elucidate the efficacy of ICB therapy using blood MSI and blood PD-L1 as biomarkers for response to therapy.

e15049 Background: Programmed death ligand-1 (PD-L1) protein expression by immunohistochemical staining (IHC) correlates with response to immune checkpoint inhibitor (ICI) therapies in non-small cell lung cancer (NSCLC). Tumor mutational burden (TMB) is another immune biomarker of ICI response in NSCLC. Clinical studies indicate tissue PD-L1 protein expression and TMB are independent yet complementary. Both are limited by tissue acquisition and potential heterogeneity. Plasma cell free PD-L1 RNA (cfRNA) levels and tissue protein PD-L1 expression and TMB was analyzed and correlated in patients with advanced NSCLC. Methods: Patients with advanced NSCLC underwent complementary plasma and tissue next generation sequencing (NGS) with immune biomarkers prior to treatment. Plasma PD-L1 cfRNA was assessed by the Circulogene proprietary direct-on-specimen enrichment technology NGS platform. Correlating tissue testing was performed by the Caris Molecular Intelligence platform with the anti-PD-L1 22C3 IHC antibody and TMB measuring the total number of non-synonymous somatic mutations per megabase. Results: 107 patients with advanced NSCLC were evaluated with simultaneous plasma and tissue NGS testing. 17% (95% confidence interval [CI] 10-24%) patients plasma PD-L1 positive. 48.5% (CI 38-57%) tissue IHC PD-L1 positive. 7 of 18 plasma PD-L1 positive patients were tissue PD-L1 negative. 48% (CI 39-58%) total patients TMB ≥ 10 mutations per megabase (TMB high). Correlating TMB high in 72% (CI 50-94%) of plasma PD-L1 positive and 56% (CI 42-69%) of tissue PD-L1 positive patients. TMB high in 49% (CI 37-59%) plasma PD-L1 negative and 50% (CI 35-65%) tissue PD-L1 negative patients. Conclusions: Although less frequent than tissue PD-L1 protein expression, plasma PD-L1 cfRNA expression correlated with a higher association of tissue TMB high findings than tissue PD-L1 positive patients. There was not any TMB high difference between plasma PD-L1 negative and tissue PD-L1 negative patients. Over one-third of plasma PD-L1 positive patients were tissue PD-L1 negative. Clinical correlation with immune checkpoint inhibitor therapies is ongoing.

e20692 Background: Liquid biopsy is an evolving minimally invasive technique to detect cell-free DNA (cfDNA) and cfRNA mutations by next generation sequencing (NGS) in plasma. In our Thoracic Oncology Program, we compared plasma liquid biopsy and tissue-based NGS assay results. Methods: Circulogene Theranostics Personalized Gene Profile (CGP), a 50-gene plasma NGS panel with proprietary direct-on-specimen enrichment technology, and tissue Caris Molecular Intelligence (CMI) NGS cfDNA and cfRNA including microsatellite instability (MSI)/microsatellite stability (MSS) and total mutational burden (TMB) results were retrospectively compiled and compared upon diagnosis. Results: 106 non-surgical lung cancer patients (median age 65 years, range 27-88; 66 men, 40 women) underwent CGP testing. 49 patients had sufficient tissue for comparative CMI. MSI detected in 20.4% (10/49) by CGP; no tissue MSI was found by CMI (0/44). 3 out of 4 (75%) MSI detected by CGP had high TMB ≥ 10 mut/Mb by CMI. 75% MSS patients by CGP had low TMB (12/16). Comparative plasma versus tissue mutations findings: TP53 mutations 60.3% (64/106) CGP and 69.3% (34/49) CMI. CGP TP53 mutated patients, high TMB 70.5 % (20/34) by CMI; EGFR mutations 13.2% (14/106) CGP and 14.2% (7/49) CMI; KRAS mutations 2.8 % (3/106) by CGP versus 28.5% (19/49); one ROS1 by CGP missed by CMI and one ALK by CGP insufficient tissue CMI. A higher frequency of BRAF 16.9% (18/106), PIK3CA 28.3% (30/106), PTEN 22.6% (24/106), and MET 7.5% (8/106) alterations was identified by plasma/CGP than comparative tissue/CMI 6.1% (3/49), 2% (1/49), 6.1% (3/49), and 0% (0/49) respectively. Conclusions: Our findings indicate that Circulogene liquid biopsy NGS detected common mutations, including actionable variants in lung cancer, providing expanded and complementary tumor molecular biology and therapeutic information to tissue NGS.

e14200 Background: Lung Cancer remains the major cause of cancer related mortality in the state of North Carolina. There is a growing body of evidence that implicates inflammation as a mechanism of disease progression and reduced survival in patients with advanced cancer (Laird et al, Oncologist 2013). Smoldering inflammation in the tumor microenvironment regulates and escalates cancer invasion, angiogenesis and immune surveillance escape (Balkwill and Mantovani, Lancet 2001). We investigated the predictive value of inflammatory signature according to social stratification of cancer patients using Modified Glasgow Prognostic Score (mGPS). mGPS is a composite inflammatory score based on CRP and serum albumin with proven prognostic and predictive value in various tumor types. Methods: A prospective observational single institutional study was conducted whereby serum albumin and CRP were drawn at baseline for 333 patients with diagnosis of cancer regardless of stage from 30 counties in Eastern North Carolina. The mGPS score was compared according to rural urban divide and occupational regional exposure of various counties stratified per US Census Data. Results: Lung cancer was the predominant cancer type in 93% of patients. The mGPS of zero in Urban vs Rural counties was noted in 36% and 24% patients respectively. The mGPS score of two in Urban vs Rural counties was noted in 26% and 41% respectively. The mGPS of two in areas of hog farming, cattle farming and wet waste lands was seen in 41%, 38% and 43% respectively (p = 0.0019). The mGPS of zero was seen in 24%, 20% and 27% respectively (p = 0.0008). Conclusions: This study suggests a strikingly unfavorable inflammatory signature in rural population as well as areas of hog farm, cattle farm and wet waste lands. The hog and poultry operations heighten the harmful effect on waterways and can adversely affect the inflammatory signature, hence the tumor biology. This underscores additional interventions in these high risk populations that can have significant implications for quality of life and survival, especially in the era of immunotherapy.

2626 Background: Early data suggests that co-occurring genetic events define biological heterogeneity in K-RAS mutant NSCLC, with K-RAS/ TP-53 (KP) co-mutated subset having potential therapeutic vulnerabilities to immune checkpoint blockade (ICB). To explore the immunological basis for these findings, we evaluated the immune biomarker profile (TMB/PD-L1) in KP mutant m-NSCLC using a large next-generation sequencing (NGS) dataset. Methods: Caris life sciences NGS dataset consisting of 1317 m-NSCLC tissue samples from 2016-18 was queried. PD-L1pos was defined as ≥ 1% staining using 22c3 Dako assay. TMB was measured by counting all somatic non-synonymous missense mutations using targeted NGS (592 genes). TMB-high (H) was defined as ≥ 10 mutations/Megabase (mut/Mb). P-values were calculated using Chi-square and Mann-Whitney test. Results: K-RAS mutations were identified in 28.7% (378/1317). Within this K-RAS mutant group, KP subset constituted 49.4% (187/378), remaining were K-RAS mutated/ TP-53 wild type (K-Pwt). 72.2 % (135/187) of KP had PD-L1pos with 51.9% (97/187) having PD-L1 ≥ 50%. KP had higher median TMB vs. K-Pwt (14.5 vs. 9.0 mut/Mb, pneg group, KP had higher % of TMB-H vs. K-Pwt (86.5 vs. 41.5%, pneg subgroup. Metastatic site-specific variations in TMB were also observed for the KP subset. These findings could have therapeutic implications in guiding patient selection for ICB and merit prospective investigation.[Table: see text]

118 Background: Immune-related adverse events (irAEs) due to immune-checkpoint inhibitors (ICI) can lead to significant morbidity. Immune pneumonitis (IP) constitutes one of the common irAEs in non-small cell lung cancer (NSCLC) with a reported incidence of 3-5%. However outside of clinical trials there is a paucity of data regarding incidence/outcomes of IP in nivolumab (N) treated metastatic-NSCLC (m-NSCLC). Methods: We retrospectively pooled data of 381 m-NSCLC patients (pts) from four cohorts treated with N within different treatment time periods: East Carolina University, USA: 4/2015- 2/2018; Ohio State University, USA: 6/2013-6/2016; University of Perugia, Italy: 10/2013-9/2017, and Sendai Kousei Hospital, Japan: 1/2016-1/2018. IP identification was based on clinical diagnosis of treating team. Grade (G) was based on Common Terminology Criteria for Adverse Events (CTCAE v 4.03). Time to immune pneumonitis (TTIP) was the time from starting N to diagnosis of IP. Results: The rate of IP was 13.1% (n=50) with 68% of IP presenting as the index irAE. Median TTIP was 9.75 weeks (range: 0.25-73.7) with G1 (24.0%), G2 (36.0%), G3 (36.0%), G4 (4.0%). 57.9% of IP ≥G2 had TTIP ≤ 3 months (m). For all-G (IP), 22.0% pts had stopped N before IP either due to non-IP irAEs or progression. Excluding these, treatment discontinuations (d/c) attributed to IP ≥ G2 were 66.6%. IP ≥G2 had higher treatment d/c when TTIP was ≤ 3m vs. > 3m (51.8% vs. 14.8%; P=0.09). Median overall survival (OS) by log rank test for pts with any grade IP vs. no IP was not statistically significant (13.7 vs. 7.5m; P =0.14). IP ≥G2 occurring at > 3m had longer median OS vs. IP ≥G2 occurring in ≤3m (16.7 vs. 3.6m, P=0.008), which was not significant at a 3m landmark analysis when accounting for time on N (P= 0.31). Conclusions: Our real-world multi-institutional data shows a higher incidence of IP in m-NSCLC. We also see a trend for frequent ICI d/c in IP ≥ G2 occurring within 3 months that may ultimately influence OS per our landmark analysis. Thus aggressive and early symptom management specifically directed at allowing reinitiation of ICI after IP needs to be considered.

e21070Background: In lung cancer patients receiving immunotherapy, radiographic disease progression (PD) has poor correlation with overall survival (OS) due to unconventional response patterns. The...

e15122Background: Quantification of baseline systemic inflammation using readily available peripheral blood-derived inflammatory biomarkers such as CRP has demonstrated prognostic and predictive ut...

e15109Background: Recent evidence indicates that the gut microbiome modulates immunotherapy responses in multiple tumor types. Some studies report antibiotics (ATB) may alter the microbiota composi...

e21134Background: In advanced non- small cell lung cancer, when compared with Docetaxel, the absolute improvement in one- year overall survival (OS) with nivolumab monotherapy (Checkmate 017 and 05...

e14606 Background: Immune checkpoint blockade(ICB) has revolutionized the treatment of a growing number of malignancies. Real world administration of oncolytics is often associated with increased adverse event rates versus what is demonstrated in clinical trials. Whether the tumor biology, site of disease burden or underlying organ dysfunction dictates the differing immune side effect profile in various malignancies remains to be understood. Methods: The incidence of grade 2-4 irAE was abstracted from medical records of all patients (pts) treated with ICB (ipilimumab and/or nivolumab) from 2011 to 2016 at a single institution. Results: Of the 126 pts reviewed, 82 pts had metastatic lung cancer, 31 pts had unresectable or metastatic melanoma, 13 pts had metastatic renal cancer(RCC). In the melanoma cohort, concurrent or sequential PD-1 and CTLA4 blockade was used in 10/31 pts. All of the lung cancer and RCC patients received anti-PD-1 alone. In the patients with lung cancer: pneumonitis was identified in 24%, SIRS in 16%, thrombosis in 11%, cerebritis in 9%, colitis in 4%, hepatitis in 4%, thyroiditis in 5%. In RCC, 8% pts experienced pneumonitis and 8% had thyroiditis. In the melanoma population, colitis was identified in 19%, SIRS in 10%, pneumonitis in 3%, thrombosis in 6%, adrenalitis in 6%, hepatitis in 3%. Colitis was seen in 2/13(15%) pts who got ipilimumab alone and 4/10(40%) pts who got both ipilimumab and nivolumab. Conclusions: Pneumonitis, SIRS and cerebritisappear to be the most prevalent irAEs in lung cancer as compared to melanoma or RCC. The incidence of pneumonitis was higher in RCC compared to melanoma. Colitis appears to have a higher incidence in melanoma, the incidence of which further increases when CTLA4 inhibitors are used in conjunction with anti-PD-1. The majority of the RCC patients tolerated ICB with no major irAEs. With the expanding use of ICB in advanced malignancies, increased awareness of these clinically significant and potentially serious irAEs is indispensable. Future trials designed to distinguish the incidence of irAEs in relation to specific tumor types would be informative. [Table: see text]

e21712 Background: Immune checkpoint inhibitors are poised to revolutionize the management of a growing number of malignancies. Unfortunately, the management of steroid-refractory immune mediated adverse events (irAEs) is based on a paucity of randomized data and limited to single center experiences. Our initial experience with the IL-6 receptor antagonist tocilizumab showed clinical improvement in a wide variety of irAEs. As a result, we adopted the use of tocilizumab for the management of steroid-refractory irAEs. Methods:The character and clinical course of irAEs were abstracted from the medical record and analyzed. The dose of tocilizumab was 4 mg/kg given IV over 1 hour. C-reactive protein was drawn at first nivolumab infusion and at q 2 weeks (and with irAEs) thereafter. Clinical improvement was defined as either: documentation of resolution of symptoms or hospital d/c within 7 days. Results:Of the initial 87 patients that were treated with nivolumab, 34 required tocilizumab (39.1%). All pts were on corticosteroids. The majority (88.2%) were lung cancer patients. The index grade 3/4 irAE was pneumonitis in 35.3%, cytokine release syndrome/SIRS in 35.3%, cerebritis in 14.7% and one case each of hypophysitis, colitis, pancreatitis, hepatitis and immune mediated coagulopathy. Median time between first nivolumab and initiation of tocilizumab was 76 days (range 1-429). Median CRP at initial tocilizumab dose was 100.5 mg/L (2.0 -350.4). Clinical improvement was noted in 27/34 pts (79.4%). 52.9% of pts required a single dose, while 35.3% required two, 8.8% required three and 1 pt required 4 doses. Twenty seven doses were given in the inpatient setting (49.1%). Median time to discharge was 4 days (range 1-27). Seventy four percent of pts were discharged home. For the 55 doses of tocilizumab that were delivered there was a cost savings of $147,174.94 (WAC) during the 18 month period versus infliximab 5 mg/kg IV dose. Conclusions: Tocilizumab is a therapeutic option for the management of steroid refractory irAEs secondary to immune checkpoint blockade. However, randomized trials are needed to better elucidate the relative efficacy and safety of these agents.

e13072 Background: There is a growing body of evidence that implicates inflammation as a mechanism of disease progression and reduced survival in patients with advanced cancer (Laird B et al. Oncologist 2013;18:1050-5.). Specifically, elevated c-reactive protein (CRP) levels have been associated with a severe symptom burden including pain, dyspnea, fatigue, nausea/vomiting, impaired quality of life, and inferior overall survival (Laird B et al. Oncologist 2013;18:1050-5.). The Modified Glasgow Prognostic Score (mGPS) is a composite inflammatory score based on CRP and serum albumin with proven prognostic value in patients with advanced lung cancer (Simmons CP et al. Lung Cancer 2015;88:304-309.). There is a significant body of evidence supporting the use of the mGPS in both Europe and Asia but the significance of the mGPS in a North American population has not been completely elucidated. We present preliminary data from a group of patients from Eastern North Carolina. Methods: Serum albumin and CRP were drawn at baseline and patients were followed for clinical course and overall survival. Patients with a dx of cancer were included regardless of stage. Clinicopathological features were abstracted from the chart and compared to a similar population from Europe (Simmons CP et al. Lung Cancer 2015;88:304-309.). Statistical comparisons were done by chi-squared test. Results: Two-hundred and twenty seven patients were eligible. Of these, 110 had either stage IV NSCLC (N= 97) or extensive stage small cell lung cancer (n=13). Median CRP was 21.9 mg/L (0.01 - 329.5). Median serum albumin was 3.4 g/dl (2.3-4.6). The number of patients with mGPS of 0, 1, and 2 were 27 (24.5%), 37 (33.6%) and 46 (41.8%), respectively. As compared to the population from Europe, the chi squared statistic was 10.1229 (p = 0.0063). There was no significant association between mGPS and race (p = 0.2277) or gender (p=0.0607). Conclusions: Lung cancer patients in Eastern North Carolina possess a strikingly poor inflammatory signature with significant implications for quality of life and survival. [Table: see text]

e20513 Background: Immune checkpoint blockade(ICB) has revolutionized the treatment of progressive NSCLC with its durable benefit when compared to cytotoxic agents. In the era of personalized medicine, there is a need to identify effective predictive biomarkers to detect exceptional responders to ICB. Immune modulating interventions with cytotoxic or biologic agents can maximize clinical responses from ICB in poorly immunogenic tumors. KRAS mutations are a negative prognostic factor for survival and generally lack targeted therapies. The T790M mutation in EGFR is the most common cause of acquired resistance to first line TKIs. As a group, patients with EGFR mutations generally do not derive clinical benefit from ICB versus cytotoxic chemotherapy. Preclinical data suggests that mutations like T790 m are associated with higher immunogenicity leading to avid stimulation of antigen specific T-cells (Ofuzi et al, 2014) and better response to ICB (Yamada, 2013). However, the efficacy of ICB by specific molecular mutations remains poorly defined. Methods: We reviewed data for 83 pts with recurrent or progressive metastatic lung cancer treated with nivolumab from June 2015-Dec 2016. All pts were treated with ICB as a second or subsequent line of treatment. The patients were assessed for pathology, mutational status and overall survival. Mutational status was checked on either tissue biopsy or serum samples submitted for proteomic veristrat/genestrat (Biodesix Inc., Boulder, CO, USA) assay. Results: Of the 83 patients treated with nivolumab, 65 patients were found to have NSCLC. Eleven pts were found to have KRAS mutation which was further subdivided as: 6 pts with KRAS G12C, 4 with KRAS G12V, 1 with KRAS G12D. Two pts were found to have T790M mutation. 81%(9/11) pts with KRAS mutation died. Median survival in pts with KRAS G12C mutation was 10 weeks and KRAS G12V was 12 weeks (p = 0.17). Median survival was not reached for patients with T790M mutation. Conclusions: KRAS mutations tend to have a shorter overall survival with ICB as compared to patients with EGFR T790M mutations. Further studies are necessary to isolate poorly immunogenic subtypes of NSCLC and develop novel treatment approaches to optimize outcomes.

e20512 Background: Veristrat (Biodesix, Boulder, CO) is a blood based proteomic assay that is dominated by inflammatory proteins and is prognostic and predictive in metastatic NSCLC after treatment with platinum based chemotherapy (Gregorc et al, Lancet 2014). Smoldering inflammation in the tumor microenvironment regulates and escalates cancer invasion, angiogenesis and immune surveillance escape (Balkwill and Mantovani, Lancet 2001). There is preclinical evidence to suggest that the tumor microenvironment can be altered with immunomodulatory interventions (Martino et al, 2016). While immune checkpoint blockade has shown durable benefit in metastatic NSCLC, the response rates still hover around 20%. As a result, identification of predictive biomarkers are of critical importance. The predictive value of the Veristrat assay with respect to ICB is poorly defined. Methods: At our institution, 83 pts with metastatic lung cancer pts were treated with nivolumab between 6/2015 to 12/2016. The following clinicopathologic characteristics were abstracted from medical records: tumor histology, Veristrat status, no. of doses of nivolumab, irAEs and overall survival. Results: Of the 83 pts, 65 pts were found to have NSCLC. Veristrat status was available for 17/65 of these pts. Nine pts were identified to have “Veristrat good” and seven pts were “Veristrat poor”. Median number of nivolumab doses was 4. Median survival for all patients was 30 weeks. Median survival was 20 weeks for “Veristrat poor” and 26 weeks for “Veristrat good”(p = 0.68). Grade 3-4 irAEs were noted in 5/9 patients with “Veristrat good” and 5/7 patients with “Veristrat poor”. Conclusions: “Veristrat poor” pts treated with ICB have a lower median survival as compared to “Veristrat good” pts. Our study did not meet statistically significant end point due to limited sample size. Further studies are needed to identify poorly immunogenic tumors and develop novel treatment approaches to optimize outcomes. [Table: see text]

38 Background: Immune checkpoint inhibitors have shown promising responses in advanced lung cancer as well as a number of other malignancies. However, efficacy appears to be variable based on the site of disease. We reviewed the outcomes of patients with lung cancer and hepatic metastases from a single institution. Methods: We performed a retrospective analysis of the lung cancer patients treated at East Carolina University with the PD1 inhibitor Nivolumab. Patients were enrolled in an IRB approved study designed to evaluate predictive markers of response to immune checkpoint blockade. Clinical characteristics, laboratory data, and imaging studies were analyzed and recorded. Results: Data for 75 patients with lung cancer who received anti-PD1 therapy was analyzed. Of the 75 patients included, 13% (n = 9) had liver metastases. Average age of the patients was 61.8 years, 66% patients were male, 22% had squamous cell, 33% had adenocarcinoma and 44 % small cell neuroendocrine histology. Average number of prior therapies was 1.7 (range 1-4). Thirty three percent of patients had modified Glasgow prognostic score of 2 and a mean CRP of 63.61mg/L (range 0.1-172.7mg/ L) at the initiation of anti-PD1 therapy. They received an average of 4 cycles of anti-PD1 therapy. Forty four percent of patients received adjunctive therapy such as ablative radiation (33%) or immune modulating chemotherapy with the aim of augmenting the effect of the anti-PD1 therapy. None of the analyzed patients with liver metastases had an objective decrease in liver metastases and the average survival in these patients after starting anti-PD1 therapy was 132 days. Conclusions: To our knowledge, this study is the largest reported series examining patients with hepatic metastases from lung cancer treated with PD-1 inhibitors. Our observations are consistent with prior reports indicating poor outcomes with anti-PD1 therapy in patients with liver metastases. The mechanisms underlying such resistance must be elucidated so that more effective treatment combinations can be developed.

3061Background: Immune checkpoint blockade has emerged as an attractive treatment option in a wide spectrum of malignancies. Optimal use of these agents requires prompt recognition and management o...

632 Background: To compare the areas of residual disease after neoadjuvant pelvic radiation with 5-FU based chemotherapy for rectal cancer using Intensity Modulated Radiation Therapy (IMRT) with simultaneous integrated boost (SIB) technique compared to 3D Conformal Radiation Therapy (3DCRT) Methods: Fourty nine (49) consecutive rectal cancer patients treated with pelvic radiation and concurrent 5-FU based chemotherapy were analyzed. We compared twenty-eight (28) patients treated on an institutional IMRT protocol versus twenty-one (21) patients treated with 3DCRT. All patients received 45-50.4 Gy to the pelvis in 3DCRT group. All patients with IMRT received 45 Gy in 25 fractions to the pelvic no des. The primary rectal tumor recieved a simultaneous integrated boost to a dose of 50 Gy in 25 fractions. IMRT planning was done with dose constraints for bladder, rectum, and small bowel and bone marrow. All patients in both groups received 5-FU based chemotherapy during radiation. Evaluation of toxicity was based on RTOG criteria. 2 patients in the 3DCRT group and 2 in IMRT group received either growth factors or blood-products transfusion and needed hospitalization during treatment secondary to acute toxicities. Results: All patients completed their prescribed course of radiation. CR rates were 5/21(23%) in 3DCRT and 4/28(25%) in the IMRT-SIB (p-value 0.74). 9/21(42%) in 3D and 19/29(65%) in the IMRT group underwent Low anterior resection according to the location of the tumor. There was no grade 4 toxicity in the IMRT-SIB group. Overall grade 2 toxicity in 3D Vs IMRT-SIB group was - GI -52% Vs 19%, GU- 8% Vs 8%, skin 42 Vs 4%, hematologic 33 Vs 47%. Overall Grade 1 toxicity in 3DCRT Vs IMRT group was- GI- 33% Vs 52%, GU 23% vs 28%, Skin 52% Vs 38%, hematologic 4% Vs 33%. Conclusions: Neoadjuvant pelvic radiation with 5 FU for rectal cancer has similar local control rates. There is less GI, skin and hematologic toxicity when delivered via IMRT-SIB versus 3DCRT. IMRT is safe and may allow dose escalation with potential probability of increased tumor response.