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4519 Background: INDUCE-1 is a first-in-human trial evaluating fela, an IgG4 ICOS agonist non-T-cell depleting mAb, as monotherapy (mono) and in combo with P. ECs include tumor types, such as UC, with high ICOS expression and immunotherapy-favorable features. Fela induced IFNγ, increased PD-1/L1 expression, and enhanced antitumor activity in combo with PD-1 blockade nonclinically. We report preliminary efficacy, safety, and biomarker data of fela ± P in INDUCE-1 UC ECs. Methods: Eligible patients (pts) had recurrent/metastatic (R/M) UC of the upper or lower urinary tract, ≤6 prior systemic therapy lines in the advanced setting, measurable disease, and no active autoimmune disease. Pts received 0.3 or 1 mg/kg fela (mono EC; anti-PD-1/L1–experienced [exp] pts) or 0.3 mg/kg fela + 200 mg P (combo EC; anti-PD-1/L1–naïve pts) every 3 wks, up to 35 cycles until disease progression or unacceptable toxicity. Disease was assessed every 9 wks through wk 54, then every 12 wks. Archival and/or fresh biopsy tumor tissue was collected for biomarker analyses and safety assessed. Results: By Nov 6 2020, 13 anti-PD-1/L1–exp and 32 anti-PD-1/L1–naïve pts were evaluable in the mono and combo ECs, respectively. In the mono EC, median age was 69 yrs (range: 47–82), 92% of pts were male, and 85% received ≥2 prior therapy lines in the metastatic setting. In the combo EC, median age was 70 yrs (range: 42–84), 75% of pts were male, and 72% received ≥1 prior therapy line in the metastatic setting. In the mono EC, median duration of follow-up (mDoF) was 10.6 mo (range: 1.1–22.8); overall response rate (ORR) was 8% (1 partial response [PR]; 95% CI: 0.2, 36.0) with a duration of response (DoR) of 6.1 mo; disease control rate (DCR [response or stable disease for ≥9 wks]) was 23% (95% CI: 5.0, 53.8), and median overall survival (mOS) was 14.5 mo (95% CI: 2.8, NR), with 74% of pts alive at 6 mo. In the combo EC, mDoF was 9.6 mo (range: 0.9–28.3); ORR was 22% (7 PRs; 95% CI: 9.3, 40.0) with a median DoR of 8.3 months (range: 3.5–23.3+); DCR was 63% (95% CI: 43.7, 78.9), and mOS was 10.7 mo (95% CI: 5.2, 18.1), with 64% of pts alive at 6 mo. Grade ≥3 treatment-related AEs were reported for 0% and 9% of pts in the mono (N = 16) and combo (N = 44) safety populations, respectively. PD-L1 expression and ICOS-specific biomarkers are being evaluated, with promising trends observed in enrichment of clinical activity in preliminary analyses. Conclusions: Fela is the first ICOS agonist with reported single-agent activity in anti-PD-1/L1–exp relapsed/refractory UC. Fela + P in combo shows promising clinical activity and manageable safety in PD-1/L1–naïve R/M UC. Further study is warranted. Updated data to be presented. Funding: Study 204691 (NCT02723955) funded by GlaxoSmithKline in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA. Clinical trial information: NCT02723955.

2630 Background: AK117 is a novel humanized IgG4 monoclonal antibody (mAb) targeting CD47, a macrophage immune checkpoint that allows tumor cells to evade immune destruction by phagocytic cells. CD47 is a target expressed in many cancers. However, the initial dose of anti-CD47 therapy may be limited by severe anemia due to ubiquitous CD47 expression on senescent red blood cells (RBCs). Here, we present encouraging preliminary AK117 safety and receptor occupancy (RO) data from an ongoing dose-escalation study in patients (pts) with advanced or metastatic solid tumors. Methods: This is a first-in-human, phase 1a/1b, multicenter, open label, single arm, dose escalation and dose expansion study of AK117 administered intravenously to adult pts with resistant/refractory advanced or metastatic solid tumors or lymphomas. In the dose escalation phase (phase 1a), an accelerated titration followed by a 3+3+3 design was used to assess the safety and tolerability of AK117 monotherapy (dose range 0.3 mg/kg to 45 mg/kg); and determine the maximum tolerated dose (MTD). AK117 was administered QW on a 28-day treatment cycle and dose limiting toxicity (DLT) observation period. Tumor assessments per RECIST v1.1 were performed once every 8 weeks (2 cycles). Results: As of 15 Feb 2021, 15 pts were enrolled in phase 1a with DLT evaluation of the 30 mg/kg cohort currently in progress. There were no DLTs up to 20 mg/kg QW AK117, inclusive. Five treatment-related adverse events (TRAEs) occurred in 4 subjects as shown in the table below. All pts with TRAEs continue to receive AK117, except the pt on 1 mg/kg AK117 who discontinued due to disease progression. G2 anemia and G1 thrombocytopenia occurred after Cycle 1 in a pt (liposarcoma, 10 mg/kg cohort), who had a medical history of anemia (hemoglobin 119 g/L at screening). No hematological TRAEs were seen in other pts, including those who received 20 mg/kg AK117 QW. There were no infusion-related reactions (IRRs) or grade ≥ 3 TRAEs. Target engagement in the periphery was confirmed by measuring CD47 RO of AK117 on RBCs and T lymphocytes. 100% RO on RBCs and T lymphocytes was achieved after the first dose and continued to Day 8 (prior to second dose) in the 10 mg/kg and 20 mg/kg cohorts. Conclusions: AK117 is safe and well-tolerated up to 20 mg/kg QW, inclusive, with no IRRs or severe TRAEs observed. There were no hematological TRAEs, except in a pt with baseline G1 anemia receiving 10 mg/kg AK117. Unlike other anti-CD47 therapies, AK117 does not require a lower ‘priming’ dose to prevent anemia. Safety evaluation of the 30 mg/kg dose level is in progress. Full and durable RO in the periphery was seen at 10 mg/kg and above. Further evaluation of AK117 in combination with AK104, an anti-PD-1/CTLA-4 bispecific antibody, shall commence imminently. Clinical trial information: NCT04349969. [Table: see text]

TPS3649 Background: ABBV-321 (serclutamab talirine) is an epidermal growth factor receptor (EGFR)-targeted antibody-drug conjugate that consists of a humanized immunoglobulin G1 anti-EGFR monoclonal antibody conjugated to a pyrrolobenzodiazepine (PBD) dimer via a maleimidocaproyl-valine-alanine linker. Once bound, ABBV-321 is internalized, the maleimidocaproyl-valine-alanine linker undergoes proteolytic cleavage, and the cytotoxic PBD is released, causing DNA cross-links and cell death. Preclinical studies have shown cytotoxicity in numerous human xenograft and patient (pt)-derived tumor models. This first-in-human trial is assessing the safety, pharmacokinetic (PK), and preliminary antitumor activity of ABBV-321 in pts with advanced solid tumor types likely to exhibit elevated levels of EGFR. Methods: This is a 2-part, multicenter phase 1 study (NCT03234712) of ABBV-321 monotherapy in pts (≥18 years; Eastern Cooperative Oncology Group performance status 0–1) with advanced solid tumors associated with overexpression of EGFR. EGFR overexpression will be determined by centralized testing using an RNA-based assay. Primary objectives of the completed part 1 (dose escalation) were to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of ABBV-321 and assess the PK and toxicity and safety profile; part 2 (dose expansion) will evaluate safety and PK profile at the RP2D in specific cohorts (NSCLC and HNSCC). Secondary objectives include assessment of preliminary antitumor activity. Pts will receive escalating doses of ABBV-321 until the MTD/RP2D is determined. Dose-limiting toxicities will be assessed during the first cycle of dosing. Adverse events (AEs) will be evaluated per National Cancer Institute Common Terminology Criteria for AEs (version 4.03). Blood samples for PK analysis (ABBV-321, total antibody, unconjugated PBD) will be collected at designated time points throughout the study. The multinational trial is active, with the first pt screened on 1 Feb 2018. The dose-escalation phase has been completed; screening and enrollment for the expansion phase of the study in NSCLC and HNSCC is underway. Clinical trial information: NCT03234712 .

2516 Background: Improving the outcomes of patients with glioblastoma (GBM) represents one of the most significant challenges in neuro-oncology. We have observed inefficiencies in the availability and use of phase 2 data when planning phase 3 studies, and have undertaken a detailed review of key design parameters of phase 2 and 3 trials in GBM to identify and quantify the impact of this phenomenon. Methods: Studies between 2005-2019 inclusive were identified though MEDLINE search using keywords and MeSH terms, and manual bibliography searches. P2Ts were restricted to those referenced by the corresponding P3Ts. Clinical, statistical and sponsor characteristics were extracted by two reviewers (AB&AG). For each P3T, corresponding Phase 2 trial (P2T) data was “optimally matched” (OM) where same drug was used in similar schedule and similar GBM population; “partially matched” (PM) where dis-similar schedule and/or treatment setting; and “lacking” in all other circumstances. The statistical data used in the P2/3 transition were compared by Pearson Correlation, Fisher’s Exact or Chi-square testing as appropriate. Results: Of 20 P3Ts identified, 6 (30%) lacked any phase 2 data. Of the remaining 14 P3T, 9 had 1 prior P2T, 4 had 2 P2T and 1 had 3 P2T, for a total of 20 P3T-P2T pairs (called dyads). Further, there were 13 OM dyads and 7 PM dyads. OM dyads showed strong concordance for mPFS (r2= 0.95, p < 0.01) and mOS (r2= 0.84, p < 0.01), whilst PM dyads did not (p > 0.05). We identified several inefficiencies in translation from P2T to P3T. Firstly, 3 P3T had statistical assumptions of primary endpoint that may have been too optimistic. 2 of these P3Ts aimed for an expected endpoint that was higher than the actual outcomes from a matched P2T. 1 P3T was unable to reach the desired sample size. We note that 4 P3Ts had actual primary endpoint HRs that were < 0.9 but with P > 0.05. Finally, we investigated whether there were absolute thresholds for efficacy in P2Ts to inform whether to proceed with P3Ts. For P2Ts in the newly diagnosed setting, all those with mPFS < 14 months and/or mOS < 22 months had subsequent negative P3Ts. For P2Ts in recurrent disease, all those with mPFS < 6 months and mOS < 12 months had negative P3Ts. Applying these thresholds to the studies in our review, 10 of the 12 negative P3Ts (83%) with matched P2Ts need not have been initiated, sparing 4739 patients’ from unnecessary trial participation. Conclusions: Our data strongly supports the vital role of properly designed P2Ts in informing P3Ts for drug development for primary CNS tumours.

e14545 Background: Recurrent GBM is difficult to treat. Single agent checkpoint blockade has not improved outcomes. Angiogenesis is a rational drug target for rGBM and targeting angiogenesis may benefit pseudoprogression and cerebral oedema. O is a fully human monoclonal antibody (MAB) which binds to Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) with antiangiogenic and antitumour effects. P is an anti-PD1 MAB. This study aimed to identify the safety and tolerability of O combined with P and to establish a recommended phase 2 combination dose. Methods: From January to October 2019, we conducted a two-site, single arm, open-label study of O with P in patients with rGBM. Eligible patients (pts) were ≥18 years with at least one RANO-measurable lesion, KPS≥80, and had completed standard chemoradiotherapy and had no contraindications to O or P. No prior bevacizumab was allowed. A modified Toxicity Probability Interval design was used. Pts received O 12 mg/kg day 1/8/15 q21d (dose level 1) or O 16mg/kg day 1/8/15 q21d (dose level 2) in combination with P 200mg flat dose day 1 q21d. Pts were reviewed weekly and underwent DCE-MRI at baseline and 6-weekly. Treatment continued to progression, toxicity or withdrawal. Results: 9 pts, median age 53 (range 34-67) were recruited and received at least one study treatment. Median time since diagnosis was 15.6 months. 7 (78%) had KPS 90 and 2 (22%) KPS 80. 3 pts received O 12mg/kg with P, completing a median 3 cycles (range 2-6). As no Dose Limiting Toxicities (DLTs) were seen, 3 pts were treated with O 16mg/kg with expansion total 6 when no DLTs were observed. At 16mg/kg, a median of 2 treatment cycles was received (range 2-6). Treatment was ceased due to progressive disease (PD) in 8 pts with one ongoing at data cutoff. No DLTs were observed in any pts. Three grade 3 treatment emergent adverse events (TEAEs) were noted (blurred vision, fatigue, and seizure). Hemangioma is a known toxicity of O and was seen in 6 pts, with 11 grade 1 and 1 grade 2 event. 4 pts (44%) had stable disease (SD) and 5 pts (56%) had PD as best response. Conclusions: The combination of O with P was safe and tolerable at the full single agent dose of each drug. No DLTs were observed. The combination did not show efficacy in this setting. Clinical trial information: NCT03722342.

2505 Background: Isocitrate dehydrogenase 1 mutations (mIDH1) are present in >70% of patients with Grade II/III gliomas resulting in production and accumulation of (R)-2-hydroxyglutarate causing DNA hypermethylation and promoting tumorigenesis. Olutasidenib is an oral, potent, brain penetrant (Kpuu=0.4 in intact rodent), and selective inhibitor of mutated IDH1 protein. Methods: Patients (pts) with relapsed/refractory (R/R) mIDH1 gliomas received olutasidenib 150 mg BID, orally either as single agent (SA) or in combination (CO) with azacitidine in a dose confirmation phase Ib followed by efficacy evaluation phase II study (NCT: 03684811). Results: As of 31-Oct-2019, 29 pts with R/R mIDH1 glioma were treated with olutasidenib as SA (n=24) or CO (n=5). The median age was 45 yrs (range: 23-64) & 62% were male. WHO Glioma Grade (Gr) at study entry was: II (17%), III (52%) & IV (31%). Median number of prior treatments was 2 (1-5); 86% had received prior temozolomide. mIDH1 status was locally determined (IHC, NGS or PCR): R132H (86%), R132L (7%), R132C (3.5%) & unspecified (3.5%). The median duration of olutasidenib treatment for SA & CO was 4.8 (1-11.4) & 1 (0.2-2.3) months, respectively. Fifteen pts discontinued (disease progression [n=12], AE [n=1], withdrew consent [n=1], other [n=1]). For SA, the most common (>25%) TEAEs (all grades, regardless of attribution) were: fatigue (50%), nausea (50%), diarrhea (33%), ALT increase (29%) & headache (29%). For CO, TEAEs that occurred in ≥ 2 pts were: nausea (n=4), fatigue (n=2), neutropenia (n=2), ALT increase (n=2) & AST increase (n=2). There were 2 protocol defined DLTs in the CO cohort, 1 pt with Gr 4 ALT, Gr 3 AST & Gr 3 GGT elevations & 1 pt with Gr 3 ALT elevation. No pts experienced a TEAE of QTcF prolongation. SA best responses are shown in Table; CO pts are too early for response assessment. The median PFS for SA was 8.3 months. Twenty (87%) and 11 (48%) pts were alive and progression-free at 6 & 12 months, respectively. Conclusions: SA olutasidenib at 150 mg BID demonstrates acceptable safety and tolerability with preliminary clinical activity in glioma pts. Evaluation of CO is ongoing. Updated safety and clinical activity, as well as evaluations of serum/CSF PK/PD will be provided. Clinical trial information: NCT03684811 . [Table: see text]

2033 Background: Despite increasing evidence of benefit supporting CGP in personalizing cancer therapy, its widespread uptake remains limited. Barriers include low patient understanding, unmet patient expectations related to low utility, clinician concerns over cost-effectiveness, perceived value, and discomfort in management of complex genomic results. Methods: This prospective cross-institutional demonstration study was designed to evaluate implementation of CGP in the care of adult and paediatric advanced cancer pts, incorporating pt reported outcomes (PROMs), discrete choice experiment (DCE), ongoing process optimization and clinician evaluations. DNA sequencing of FFPE tumor and matched blood was completed with CGP (PMCC Comprehensive Cancer Panel; 391 genes) via central laboratory. A tumor board reported results weekly with emphasis on therapeutic relevance. Oncologists performed consent and results delivery. Pts completed pre-and post-test surveys, including validated and study-specific questions, DCE and if eligible, semi-structured interviews. Qualitative interviews were undertaken with study clinicians and laboratory staff to evaluate processes. Results: 86% (315) of 365 enrolled pts had successful CGP; of these 63% (199) had relevant therapeutic, diagnostic or germline results. 50 (16%) had treatment change at 6m, 49 (16%) had germline mutations. 293 (88% of adult pts) completed PROMs. 17 of 19 clinicians/laboratory staff approached consented to an interview. At consent pts cited multifaceted value in testing, showed good understanding of basic concepts, but most (69%) overestimated the likelihood of result-led change. Post-test pts remained consistently satisfied with accessing CGP; valuing research contribution, taking opportunities and information for family. 21% struggled with understanding results but there were low levels of decisional regret following participation (89% had nil/mild regret). Pt-elicited preferences (via DCE) indicated priority for high rates of clinical utility and timeliness. Clinicians sited collaboration and communication as critical to delivery of CGP. Conclusions: Pts undergoing CGP are generally satisfied, and derive value on its use beyond potential therapeutic benefit. Our results suggest that to improve test utility and delivery of CGP with value to pts and investing institution, focus must be placed on addressing the additional barriers to its wider implications including efforts to improve process efficiencies, clinician genomic literacy and decision-making support.

Purpose CS-1008 (tigatuzumab) is a humanized, monoclonal immunoglobulin G1 (IgG1) agonistic antibody to human death receptor 5. The purpose of this study was to investigate the impact of CS-1008 dose on the biodistribution, quantitative tumor uptake, and antitumor response in patients with metastatic colorectal cancer (mCRC). Patients and Methods Patients with mCRC who had received at least one course of chemotherapy were assigned to one of five dosage cohorts and infused with a weekly dose of CS-1008. Day 1 and day 36 doses were trace-labeled with indium-111 (111In), followed by whole-body planar and regional single-photon emission computed tomography (SPECT) imaging at several time points over the course of 10 days. Results Nineteen patients were enrolled. 111In-CS-1008 uptake in tumor was observed in only 12 patients (63%). 111In-CS-1008 uptake and pharmacokinetics were not affected by dose or repeated drug administration. 111In-CS-1008 biodistribution showed gradual blood-pool clearance and no abnormal uptake in normal tissue. No anti–CS-1008 antibody development was detected. One patient achieved partial response (3.7 months duration), eight patients had stable disease, and 10 patients had progressive disease. Clinical benefit rate (stable disease + partial response) in patients with 111In-CS-1008 uptake in tumor was 58% versus 28% in patients with no uptake. An analysis of individual lesions showed that lesions with antibody uptake were one third as likely to progress as those without antibody uptake (P = .07). Death-receptor–5 expression in archived tumor samples did not correlate with 111In-CS-1008 uptake (P = .5) or tumor response (P = .6). Conclusion Death-receptor–5 imaging with 111In-CS-1008 reveals interpatient and intrapatient heterogeneity of uptake in tumor, is not dose dependent, and is predictive of clinical benefit in the treatment of patients who have mCRC.

2032 Background: Durvalumab (durva), a human IgG1 monoclonal Ab against PD-L1, is FDA-approved for selected patients with bladder and non-small cell lung cancers. PD-L1 is expressed by some GBM tumors, while GBM infiltrating T lymphocytes often express PD-1. Radiation induced cell death releases tumor antigens and could potentiate anti-PD-(L)1 therapy. Methods: This ongoing Phase 2 open-label study (NCT02336165) evaluates the safety and efficacy of durva (10 mg/kg every 2 weeks) in 5 GBM cohorts. Results are presented for Cohort A, which evaluates durva + standard radiotherapy (RT, 60 Gy over 30 fractions) followed by durva monotherapy in patients with new unmeth GBM after maximum safe resection. The primary efficacy endpoint for Cohort A is overall survival at 12 months (OS12); secondary endpoints include safety/tolerability, tumor response rate, and progression-free survival (PFS). Historical benchmarks of median OS and OS12 for patients with new unmeth GBM following standard therapy are 12.7 months and 50%, respectively (EORTC 26981-22981/NCIC CE.3). Results: Median follow-up of 40 enrolled patients is 24.5 months (data cutoff = 05 Nov 2018). Baseline characteristics: male, 70%; median age, 57.0 [22 to 77] years; ECOG PS0, 60.0%; ECOG PS1, 40.0%; measurable disease, 80.0%; and dexamethasone use, 32.5%. Treatment-related adverse events with maximum CTCAE grade ≥ 3 occurred in 14 (35.0%) patients; the most common were asymptomatic increased lipase (n = 6) and increased amylase (n = 2). Twenty-four of 40 patients were alive at 12 months (Kaplan-Meier for OS12, 60.0% [90% CI: 46.1, 71.4]). Median OS was 15.1 (95% CI: 12.0, 18.4) months. As of 05 Nov 2018, 8 (20%) patients remain alive, with ongoing survival ranging from 15.7 to 34.9 months. Tumor immunocorrelative and systemic studies are pending. Conclusions: This is the first study report of anti-PD-L1 for new GBM. Durva was well tolerated when combined with RT and seemed to have efficacy among patients with new unmeth GBM. Further studies may be warranted. Clinical trial information: NCT02336165.

e14677 Background: Malignant mesothelioma (MM) is an aggressive malignancy of the pleura with limited therapeutic options, and is associated with a poor prognosis. EGFR is known to be highly over-expressed in mesothelioma with reported EGFR overexpression between 44 to 97%. We have investigated an anti-EGFR antibody (ABT-806), which is tumor specific and robustly inhibits EGFR-expressing tumors. We have previously shown that ABT-806 ADCs demonstrate potent anti-tumor activity in 806 immunohistochemistry (IHC) positive MSTO-211H MM cell line xenograft model. We present data in MM using ABT-806 novel ADCs [ABT-414 (ABT-806- monomethyl auristatin F), ABBV-221 (ABT-806- monomethyl auristatin E) and ABBV-321 (ABT-806- pyrrolobenzodiazepine)] in MM patient derived xenografts (PDX). Methods: We evaluated expression of EGFR and mAb 806 IHC in MM cell lines and PDXs. PDXs were implanted into 5 to 10 NOD-Scid mice per group and treated with control ADC, saline, cisplatin or ABT-806 ADCs and followed longitudinally with caliper measurements. Comparative statistics were performed in Graphpad prism. Results: Three PDX models were selected according to their 806 IHC statuses (2 epithelioid 806 IHC positive, 1 biphasic histology 806 IHC negative). In one epithelioid PDX model, ABBV-321 resulted in significantly reduced tumor growth on day 27 post therapy with median tumor volumes of 180 mm3 (ADC control) compared with 78mm3 (ABBV-321; p = 0.0159 two-sided). Moreover, the median survival was also significantly longer in ABBV-321 treated models (p = 0.018). In the other epithelioid PDX model, ABBV-321 also resulted in significant responses (median 428mm3 (ADC control) vs 167mm3 (ABBV-321, p = 0.0201). In the 806 IHC negative PDX model, the differences in tumor volumes between all groups were found to be non-statistically significant (ADC control vs ABT-414, ADC control vs ABBV-221, ADC-control vs ABBV-321 groups) with p = 0.0597 for one-way ANOVA. MSTO211H cell line xenograft model also demonstrated significant anti-tumor response to both ABT-414 and ABBV-221 (p < 0.01). Conclusions: In a disease with limited therapies, ABT-806 targeting ADCs in MM demonstrated significant responses in 806+ PDX and cell lines. These data support clinical expansion of these compounds in 806+ MM patients.

TPS42 Background: Despite recent advances in immunotherapy, many patients with advanced solid tumors are refractory to available therapies or eventually relapse. Novel immune therapies are needed with differentiated mechanisms of action that result in improved response rates and durability across a broad range of tumors. FPT155 is a first-in-class therapeutic being developed to meet this need. FPT155 is a recombinant fusion protein composed of the extracellular domain of human CD80 fused with the Fc domain of human immunoglobulin G1. It is designed to act as a potent stimulator of anti-tumor immunity through CD28 and thereby co-stimulate T cell responses only in the presence of antigenic T cell receptor (TCR) signaling. FPT155 alone does not induce spontaneous cytokine release by primary human immune cells, in contrast to a CD28 superagonist antibody that exerts TCR stimulus-independent activity. FPT155 also blocks CTLA-4 from competing for endogenous CD80, allowing CD28 signaling to prevail in T cell activation. A murine surrogate of FPT155 is a potent inhibitor of tumor growth that induces complete tumor regression in multiple tumor models, including models that are insensitive to anti-PD1 or anti-CTLA4. Methods: The FPT155-001 study is a Phase 1a/1b open-label, multicenter, dose escalation and expansion study to evaluate the safety and tolerability of FPT155 monotherapy. Phase 1a dose escalation includes an accelerated titration design followed by a standard 3+3 design until the recommended dose for Phase 1b is determined by evaluation of all available safety, pharmacokinetic (PK), and pharmacodynamic (PD) data. Eligible patients with advanced solid tumors who are refractory to all standard therapy for their malignancy will be enrolled in Phase 1a. Phase 1b dose expansion will enroll patients with select tumor types. The primary endpoint is safety in both phases. Key secondary endpoints in Phase 1a include characterization of the FPT155 PK profile and immunogenicity. Key secondary endpoints in Phase 1b include objective response rate, duration of response, progression free survival, and disease control rate. The FPT155-001 trial opened for enrollment in October 2018 and is in progress. Clinical trial information: Submitted - awaiting registration number.

Purpose The Consolidated Standards of Reporting Trials (CONSORT) guidance was extended in 2004 to provide a set of 10 specific and comprehensive guidelines regarding adverse event (AE) reporting in randomized clinical trials (RCTs). Limited data exist regarding adherence to these guidelines in publications of oncology RCTs. Methods All phase III RCTs published between 2007 and 2011 were reviewed using a 16-point AE reporting quality score (AERQS) based on the 2004 CONSORT extension. Multivariable linear regression was used to identify features associated with improved reporting quality. Results A total of 325 RCTs were reviewed. The mean AERQS was 10.1 on a 16-point scale. The most common items that were poorly reported were the methodology of AE collection (adequately reported in only 10% of studies), the description of AE characteristics leading to withdrawals (15%), and whether AEs are attributed to trial interventions (38%). Even when reported, the methods of AE collection and analysis were highly heterogeneous. The multivariable regression model revealed that industry funding, intercontinental trials, and trials in the metastatic setting were predictors of higher AERQS. The quality of AE reporting did not improve significantly over time and was not better among articles published in journals with a high impact factor. Conclusion Our findings show that some methodologic aspects of AE collection and analysis were poorly reported. Given the importance of AEs in evaluating new treatments, authors should be encouraged to adhere to the 2004 CONSORT guidelines regarding AE reporting.

2033Background: Depatuxizumab mafodotin (depatux-m, formerly ABT-414) is an EGFR-directed antibody-drug conjugate being developed for treatment of EGFR-amplified glioblastoma (GBM). As therapeutic ...

445 Background: Monoclonal antibodies (mAb) against programmed cell death-1 (PD-1) have demonstrated antitumor activity across multiple malignancies. BGB-A317 is a humanized IgG4 mAb with high affinity and binding specificity for PD-1. Previous reports from an ongoing Phase 1A/1B study (NCT02407990) in patients with advanced solid tumors suggested that BGB-A317 was generally well tolerated and had antitumor activity in multiple tumor types. Here, we present the preliminary results from a subset of patients with UC enrolled in this study. Methods: Patients with UC received intravenous BGB-A317 at doses of 2, 5, 10 mg/kg Q2W or Q3W and 200 mg Q3W. Tumor cell (TC) and immune cell (IC) PD-L1 expression was retrospectively assessed with the VENTANA PD-L1 (SP263) assay. Safety and tolerability was assessed by monitoring adverse events (AEs) and antitumor effects were assessed by RECIST v1.1 criteria. Results: As of 8 June 2017, 15 patients with UC (median age, 72 yr [range: 39–79]) received BGB-A317 during phases 1A (n = 8) and 1B (n = 7). All patients were Caucasian and 13 patients were male; the median number of prior systemic anticancer therapies was 1 (range: 0–4). Median duration of treatment was 115 d (range: 27–476); 6 patients remain on treatment. The most common treatment-related AEs (TRAEs) were fatigue (n = 5) and rash (n = 3); grade ≥3 TRAEs included fatigue (n = 1), and hyperglycemia and type 1 diabetes mellitus (T1DM; n = 1). Serious TRAEs occurred in 2 patients (infusion-related reaction [n = 1]; hyperglycemia and T1DM [n = 1]). All patients were evaluable for response assessment. Confirmed complete and partial responses occurred in 1 and 3 patients, respectively, for a response rate of 27%; the disease control rate (CR+PR+SD) was 53%. Nine samples were available for PD-L1 evaluation. Responses were observed in 3 of 6 patients with PD-L1+ tumors (defined as ≥25% TC or IC expressing PD-L1 by IHC) while 1 in 3 patients with PD-L1– tumors responded. Conclusions: BGB-A317 was generally well tolerated in patients with UC and objective responses were observed in both PD-L1+ and PD-L1– diseases. BGB-A317 is currently being investigated in China as monotherapy for patients with PD-L1+ UC (CTR20170071). Clinical trial information: NCT02407990.

e13512 Background: Multi-disciplinary team (MDT) meetings are considered essential to quality cancer care. For some malignancies, MDTs have been associated with improved outcomes, but data is limited for their utility in neuro-oncology. The aim of this study was to prospectively describe the MDT at our institution and evaluate its impact on clinical management. Methods: All cases discussed over three months at the Austin Health neuro-oncology MDT were prospectively evaluated. Cases were discussed amongst the treating team and a provisional plan (PP) and reason for discussion (RFD) was documented preceding the MDT. The PP was recorded as: surgery, radiation, chemoradiation, further diagnostic tests, surveillance and other. Patient specific clinical data was captured prospectively, with further pathological and radiological information captured during the MDT. Subsequently, the MDT reached a consensus decision, which was recorded. High impact decisions (HID) were those in which a substantial modification to the PP was made. Subsequent data regarding patient adherence to the MDT plan was recorded. Results: Over the period 79 cases were discussed at the MDT. Twenty-seven (34%) cases were female, 52 (66%) were male. The median age was 53. Six patients were discussed more than once. Forty-three cases were new diagnoses. Forty-two cases were primary brain tumours, twenty-five were metastatic solid organ malignancies. Thirty-four per cent of cases had HID. On chi-square analysis, the RFD was not statistically associated with HID (p = 0.28), nor was the primary versus recurrent setting (p = 0.80) however, the nature of the PP was (p = 0.023). Adherence data was collected for 95% (75) of cases. Adherence to the MDT plan occurred 90% (67) of cases. For cases of non-adherence, six out of eight (75%) were due to patient choice. Conclusions: A significant proportion of treatment modifications are made following discussion at the neuro-oncology MDT. The nature of the provisional treatment plan may influence which cases are likely to have a change in management determined in the MDT. MDT recommendations are broadly adhered to, and in cases of non-adherence, are largely due to patient factors.

2042 Background: DUR is a human IgG1 monoclonal Ab against PD-L1. PD-1/PD-L1 blockade has shown benefit in solid tumors. PD-L1 is expressed by many GBM tumors while cytotoxic lymphocytes infiltrating GBM tumors often express PD-1; thus, there is a rationale for exploring PD-1/PD-L1 blockade in GBM. Bevacizumab (BEV) is a VEGF-specific angiogenesis inhibitor approved for recurrent GBM. PD-L1 blockade and angiogenesis inhibition may be synergistic. Methods: This ongoing Phase 2, multicenter, open-label study (NCT02336165) evaluates safety/efficacy of DUR (10 mg/kg every 2 wks) in 5 GBM cohorts. Secondary endpoints are safety/tolerability, median PFS/OS, overall response rate and quality of life measures. Exploratory endpoints: neurologic function and immunocorrelative biomarkers. Results: Enrollment as of 16 Dec 2016: Cohort A = 35, B = 31, B2 = 34, B3 = 34, and C = 20 pts. Enrollment is ongoing for Cohorts A and C. This is an update to the interim analysis that was reported for Cohort B (male: 83.9%; mean age: 54.0 [24-77] years; baseline ECOG PS0: 51.6%, PS1: 48.4%; baseline measurable lesions: 77.4%). Incidences of treatment-related adverse events (TRAEs) by max CTCAE grade (Gr) were Gr1: 35.5%; Gr2: 41.9%; Gr3: 9.7%; and Gr4/5: 0%. Most common TRAEs (≥3 pts): fatigue, headache, hemiparesis, gait disturbance, increased AST, and decreased platelets/WBCs/lymphs. Six of 30 evaluable pts were progression free at 6 months (Kaplan-Meier, 20.0% [90% CI: 9.7, 33.0]); best overall response: partial response, 4 (13.3%) pts and stable disease, 14 (46.7%). At 1 year, 4 pts remained progression free (longest PFS ongoing at 80 wks, n=2). OS-6 and OS-12 are 59.0 and 44.4%, respectively. As of 16 Dec 2016, 7 pts remain alive (longest OS ongoing at 86 wks). Conclusions: DUR monotherapy appears to be well tolerated and shows durable activity in a subset of BEV-naïve recurrent GBM pts. Study is ongoing. Clinical trial information: NCT02336165. [Table: see text]

2003 Background: GBM is the most common malignant primary brain tumor in adults. Pts with rGBM have a poor prognosis. EGFR is amplified (amp) in ~50% of GBMs and is a compelling therapeutic target. ABT-414 is an antibody-drug conjugate composed of an EGFR-directed antibody conjugated to a microtubule toxin, MMAF. ABT-414 binds a unique epitope exposed during EGFR activation, either through ligand stimulation or mutation such as EGFR variant III (EGFRvIII), releasing MMAF into the cancer cell. Here, we report a pooled safety and efficacy analysis of ABT-414 +/- TMZ in EGFR amp, rGBM. Methods: M12-356 is a Phase 1, open-label, multi-arm study. Results from the 2 arms accruing rGBM pts were pooled for analysis. Eligible adults had rGBM, centrally confirmed EGFR amp, and KPS ≥ 70. Pts received 0.5-1.25 mg/kg ABT-414 on days 1 and 15 +/- 150-200 mg/m2 TMZ on days 1-5 of 28-day cycles until progression (per RANO). Results: As of 11 January 2017, 126 pts were treated. The most common adverse events (AEs, ≥ 25% pts) were ocular (90%) and included blurred vision (64%) and photophobia (31%), which were mainly reversible. Common non-ocular AEs were fatigue (36%) and headache (30%). Grade 3/4 AEs (≥ 5% pts) included ocular toxicities (29%) and decreased platelets/thrombocytopenia (10%). Serious AEs included seizure and keratitis (2% each). Of 125 pts evaluable by RANO, 52% had improvement or stabilization as best response (2 CR, 9 PR, 54 SD), and the remaining 60 (48%) had PD. Of 115 pts with measurable disease at baseline, the objective response rate (ORR) was 10% (2 CR + 9 PR). For 5 pts, re-resection for radiographic PD revealed mostly necrotic tissue and pts were classified as SD, suggesting the ORR may be an underestimate. Of all 126 pts, the 6-month PFS rate (PFS6) was 26%; median OS was 8.5 months. Conclusions: In this Phase 1 trial of EGFR amp, rGBM, we observed encouraging disease control (52%, CR + PR + SD) and PFS6 (26%) rates. Toxicity was mainly ocular, and reversible. A global, randomized trial of ABT-414 vs. ABT-414 + TMZ vs. TMZ/lomustine in EGFR amp, rGBM has completed accrual with results expected later this year (NCT02343406). Clinical trial information: NCT01800695.

TPS3113 Background: Inducible T cell Co-Stimulator (ICOS), a member of the CD28/B7/CTLA-4 receptor superfamily expressed on T cells after engagement with cognate antigen and activation, provides a co-stimulatory signal augmenting T cell proliferation, survival and cytokine production. GSK3359609 is a humanized IgG4 antibody selected for its potent agonist activity against human ICOS. The unique mechanistic profile of an ICOS agonist antibody, such as GSK3359609, offers an opportunity to investigate the antitumor potential of targeting a T cell co-stimulator alone and in combination with other cancer immunotherapies such as pembrolizumab. Methods: INDUCE-1 is a first- in-human study evaluating safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity of GSK3359609 administered as an intravenous (IV) infusion once every 3 weeks (Q3W) alone (Part 1) and in combination with 200 mg pembrolizumab (Q3W IV infusion) or other immunotherapy (Part 2) in approximately 304 adult patients. In dose escalation, eligible patients are required to have selected relapsed/refractory solid tumors. Primary objective is to determine safety, tolerability, and maximum tolerated or administered dose. Modified toxicity probability interval method will inform dose escalation decisions (minimum 3 patients per dose level [DL]). In expansion, cohorts may be defined by factors such as tumor histology, biomarker features, or prior treatment. More than one GSK3359609 DL may be evaluated in an expansion cohort by random assignment. Blood immunophenotyping is monitored in all patients; tumor biopsies (before and on-treatment) are optional in escalation and required in expansion to provide biomarker data that may inform on optimal dose selection as well as mechanistic understanding of GSK3359609. Efficacy measures are every 9 weeks and are according to immune-related RECIST. As of 7 Feb 2017, the first 3 monotherapy DL cohorts completed without dose limiting toxicities; DL 4 enrollment is ongoing. Study is funded by GlaxoSmithKline and is in collaboration with Merck & Co., Inc. Clinical trial information: NCT02723955.

3066Background: BGB-A317 is a humanized IgG4 anti-PD-1 mAb with high specificity and affinity (KD = 0.15 nM) for PD-1. It blocks PD-L1 and PD-L2 binding, and inhibits PD-1-mediated negative signali...

e17049Background: BGB-290 is a novel highly-selective inhibitor of PARP1/2 with potent DNA-trapping activity. It had excellent oral bioavailability and DMPK properties in animal studies. In additio...

TPS2077 Background: Programmed cell death ligand-1 (PD-L1) is widely expressed on antigen presenting cells (APC) and other immune cells. PD-L1 binds two important regulatory receptors on T-cells: p...

2016 Background: GBM remains almost universally fatal and new therapies are needed. The epidermal growth factor receptor (EGFR) is a key oncogenic target. ABT-414, an antibody-drug conjugate with a...

487 Background: Met is a receptor tyrosine kinase that is deregulated across multiple cancer types, leading to uncontrolled tumor cell growth, invasion and survival. MET is frequently dysregulated in PRCC. Activating Met mutations are present in hereditary and a subset of sporadic PRCC cases (up to 21% of type I PRCC, Albiges et al, 2014). Trisomy of chromosome 7 (containing both MET and HGF genes) has been reported in 45-75% of sporadic PRCC cases; 81% of type I and 46% of type II PRCC have copy number alterations of MET (Albiges et al, 2014). Methods: AZD6094 (HMPL-504/volitinib) is a potent, selective Met inhibitor. Preclinically, AZD6094 inhibits in vitro growth of MET-amplified gastric and lung cell lines. In vivo AZD6094 induces regressions in PRCC explant models. Results: In phase I, AZD6094 was well tolerated, with good exposure and low accumulation (Gan et al, 2014). Two PRCC pts in the 600 mg QD cohort (one with ongoing treatment at 19 months) and 1 PRCC in the 1,000 mg QD cohort (ongoing treatment at 13 months) achieved PR. A fourth patient, on 300 mg BD, showed a best tumor response of 25% decrease from baseline. Analysis of tumor samples showed that all the responders had MET copy number increase. Conclusions: These encouraging findings have triggered a phase II trial. This is an open label non-randomised multi-centre study to assess the efficacy of AZD6094 monotherapy in treatment naive and previously treated PRCC patients. Eligibility includes PRCC histopathology, ECOG status 0 or 1, ability to comply with the collection of tumor samples, adequate haematological, liver, and kidney function, and measurable disease (RECIST 1.1). The study is ongoing in collaboration with Sarah Cannon Research Institute in the United States, Canadian, EU centres. This study is sponsored by AstraZeneca, clinical trial information: NCT02127710. Clinical trial information: NCT01773018.

11111 Background: Volitinib is a selective oral small molecule inhibitor of cMet kinase with potent in vivo inhibitory effects on a variety of human tumor xenografts. Methods: This phase I, first-in-human dose-escalation study was conducted to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics (PK) profile, and preliminary antitumor activity of volitinib. Results: By Dec 31, 2013, 32 patients (pts) had been enrolled and treated with volitinib at doses of 100-1000mg QD or 300-400mg BID. Pts had a median age of 61 (27-78) yrs, 66% were male. The most common tumor types were papillary renal cell carcinoma (PRCC, 6) and CRC (5). The most common adverse events were constipation, diarrhea, fatigue, nausea, vomiting, dizziness and peripheral edema, mostly grade (G) 1/2. Four pts reported 5 DLTs: 1 G3 elevated ALT (600mg QD), 1 G3 fatigue (800mg QD), and 2 G3 fatigues and 1 G3 headache (1000mg QD). 800mg was identified as MTD of the QD regimen. Dose-escalation in the BID...

2021 Background: Patients (pts) with recurrent GBM have few treatment options and a very poor prognosis. GBM tumors often exhibit aberrant epidermal growth factor receptor (EGFR) proliferative sign...

2583 Background: Death receptor 5 (DR5) is a member of the TNFR superfamily that initiates the extrinsic apoptotic pathway. CS-1008 is a humanised, monoclonal IgG1 agonistic antibody (Ab) to human DR5 created by CDR grafting of the murine Ab TRA-8. The aim of this study was to investigate the impact of CS-1008 dose on biodistribution, quantitative tumor uptake and anti-tumor response in pts with mCRC. Methods: Pts with mCRC were treated with weekly IV CS-1008 in 5 non-sequential cohorts (Co). Different loading doses were used on days 1 and 8 (0.2 to 6 mg/kg), followed by a weekly dose of 2 mg/kg. D1 and D36 doses were trace-labeled with 111In, followed by whole-body planar and regional SPECT imaging over 10 days. Primary endpoints: initial biodistribution, pharmacokinetic (PK) and tumor uptake following single infusion; changes in biodistribution, PK and tumor uptake following sequential doses. Secondary endpoints: tumor response; changes in tumor metabolism by FDG-PET; serum apoptosis biomarkers and tumor response markers. Results: 19 pts (median age 64 yrs; M:F 11:8; 2-6 prior chemotherapy regimens) were enrolled as follows: Co 1, n=2; Co 2, n=4; Co 3, n=5; Co 4, n=3; and Co 5, n=5. Tumor uptake was variable: 7 pts had no uptake, 11 pts had uptake in all sites of disease but liver, 1 pt showed liver uptake. Tumor uptake and PK were not affected by dose or repeated drug administration. No anti-CS-1008 Ab responses were detected. DR5 expression in archived samples did not correlate with uptake or response. 111In‐CS‐1008 biodistribution showed gradual blood pool clearance and no abnormal uptake in normal tissue. Mean % change in SUVmax from baseline in lesions with uptake was higher than in those with no uptake. There were 8 SD, 1 PR and 10 PD. Duration of PR was 3.7 months (mo). Mean duration of SD was 4 mo. Disease control rate (SD + PR) in pts with uptake was 58% vs 28% of pts with no uptake. Lesions with no uptake were more likely to progress, with a PD risk of 3.4 times higher than those lesions with uptake. Conclusions: Tumor DR5 expression, assessed by 111In-CS-1008 imaging, revealed real-time heterogeneous DR5 expression and appeared to be a promising predictive imaging biomarker of clinical benefit in pts with mCRC receiving CS-1008. Clinical trial information: NCT01220999.

5587 Background: There is increasing evidence that NCF abnormalities may occur in cancer pts. Data on pre-treatment NCF in HNC pts are lacking. This study reports NCF in pts with newly diagnosed, curable HNC compared to controls. Methods: HNC pts underwent a 2-hour battery of NCF tests prior to radio +/-chemo(bio)therapy. Domains tested were intelligence (IQ), memory, language, attention, processing speed, executive function and manual dexterity. Test performances were transformed into Z-scores using normative data (score < -1 signified deficit). Pts also had self-reported assessments for NCF, quality of life (QOL), fatigue and affect. Data obtained were compared to non-cancer controls who underwent the same tests. Results: Eighty HNC and 30 control subjects were assessed. Objective NCF testing demonstrated that HNC and control cohorts were similar across all domains, except for IQ, with pts having higher scores (mean 0.55 vs 0.12, p=0.03). However, individual analysis showed that 39% of HNC and 43% of control subjects had abnormal Z-scores in ≥ 2 domains. Multivariable analysis of factors associated with ≥ 2 abnormal NCF domains included: low education level, significant smoking history (≥ 10 pack year), previous mild brain injury, gender, and group (pt vs control). Amongst pts, HPV -ve status and non-oropharyngeal tumors were also associated with decreased NCF. Pts reported statistically worse subjective baseline symptoms compared to controls: NCF (mean FACT-COG 33.7 vs 18.2, p=0.002), QOL (FACT H&N 33.8 vs 14.9), fatigue (FACT-F 35.1 vs 15.1), anxiety (HADS 7.0 vs 3.1) and depression (HADS 3.9 vs 1.2), p

3000 Background: FAK has an important role in cancer invasion and metastasis. FAK and phospho-FAK (pFAK) are increased in advanced cancer and are correlated with poor prognosis. GSK2256098 is a potent and specific small molecule inhibitor of FAK. Methods: This is a first-time in cancer pts, dose escalation study (NCT01138033) to identify the maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity. Part 1 used a modified accelerated titration procedure switching to standard 3+3 design based on toxicity during the first 21 days of treatment. Pts were treated with GSK2256098 orally twice daily (BID) with food. Safety was established in cohorts of 1-6 pts. After MTD determination, Parts 2 and 3 were opened to further evaluate safety, PK and PD. Serial PK samples were obtained over 24 h on Days 1 and 15. Pre- and post-dose skin, hair and tumor tissue biopsies were analyzed for pFAK. Results: 57 pts with advanced solid tumors have been treated at escalating doses ranging from 80 mg to 1500 mg BID: median age=58.8 (range 21-84). The most common tumor types include: mesothelioma (23), ovary (7), colon (3), kidney (3), and pancreas (3). MTD was determined to be 1000 mg BID. DLTs were Gr 2 proteinuria (1000 mg), Gr 2 nausea, vomiting, fatigue (1250 mg) and Gr 3 asthenia (1500 mg). Most frequent toxicities were nausea (32 pts, 56%), diarrhea (31 pts, 54%), vomiting (25 pts, 44%), decreased appetite (18 pts 32%) and asthenia (11 pts, 19%). The majority of toxicities were Gr 1-2; Gr 3 drug-related events included hypertriglyceridemia (n=2), hyperlipasemia (2), asthenia (1), increased amylase (1), and loss of consciousness (1). Few dose reductions and interruptions have occurred. Minor responses/stable disease (SD) were observed in pts with mesothelioma (-12%, 27 wks), melanoma (-26%, 54 wks), and naso/pharyngeal cancer (-31% target lesion, 30 wks) and SD in renal cell (48+ wks). In preliminary analysis of single-dose PK, exposure generally increased in a dose-proportional manner, and the geometric mean t½ was 4.2 h. Accumulation was not observed with repeat dosing. Conclusions: GSK2256098 is well tolerated with evidence of clinical activity. PK supports BID dosing.

5522 Background: There is evidence that cancer and/or its treatment can impair thinking abilities. To date, there have been no longitudinal studies exploring NCF in HNC pts. We present a prospective NCF assessment in HNC pts treated with C/B-RT. Methods: Baseline information including pt demographics, primary tumor site, stage, smoking/alcohol history, systemic therapy details and RT dosimetry were collected. All pts underwent a 2-hour battery of NCF testing at baseline and at 1-year (yr). Domains evaluated included memory, motor skills, intelligence, language, attention, processing speed and executive function (EF). Performances on the various tests were transformed to Z-scores using normative data. NCF decline was defined as a Z-score decrease of ≥-1 and improvement as a Z-score increase of ≥+1. Pts also had subjective assessments of anxiety, depression, NCF and quality of life (QOL) using the Hospital Anxiety and Depression Scale and FACT questionnaires. QOL was considered significantly altered if FACT...

2562 Background: The expected benefit of the experimental over the standard arm (δ) in a RCT is estimated based on current evidence and investigators’ experience. Overestimation of δ can lead to in...

e15153 Background: The efficacy of second-line targeted therapy (SLT) in patients with metastatic RCC who have progressed on first-line VEGFR TKI is of clinical relevance but remains to be fully de...

e19629 Background: There is increasing evidence that cancer and/or its treatment can impair thinking abilities. We recently reported on cognitive functioning (CF) in LA-SCCHN pts 1-2 yrs post RT or...

6031 Background: To improve the quality of results reported in randomized clinical trials (RCTs), international registration has been recommended. We performed a review of oncology RCTs published o...

6122 Background: The CONSORT guidelines (2001) aimed to improve the reporting of RCTs. This study examined the adequacy of data provided in oncology RCTs in selected journals (Ann Oncol/BJC/Breast ...

6068 Background: Evidence suggests cancer-related treatments affect cognition. To our knowledge, no studies have systematically investigated cognitive impairment in head and neck cancer (HNC) patients (pts). We assessed ten relapse-free HNC pts after curative-intent radiotherapy (RT), half of whom received cisplatin (Cp). Methods: Pts completed a 2-hr battery of tests/questionnaires assessing objective cognitive function (CF), subjective CF, quality of life and affect. Objective measures of CF were transformed to Z-scores (mean=0, standard deviation=1) using age normative data. A negative value for the Difference Score (DS=Z-score minus IQ score) in each tested domain indicates cognitive deterioration as IQ is a pre-morbid estimate of pts’ CF. A Global Deficit Score (GDS) was obtained by averaging the DS of all tested CF domains. Results: Pt demographics were: M:F=8:2; mean age=58 yrs(range 47–66); mean smoking pack yrs=15(0–45); mean drinks/week=7(0–25); mean IQ Z-score=+1.2(-1.0 to +2.0), mean school yrs=15 (6–18) and mean time post treatment=20 mo(9–41). All pts completed the battery within 2 hr. Nine participants appeared to have impaired CF based on negative DS and GDS scores ( Table 1 ). Exploratory univariate analyses showed trends that higher RT dose and Cp use were associated with increased impairment but cytokines, anemia, hormonal status and affective state were not. Conclusions: This feasibility study suggests cancer-related treatment affects cognition in HNC survivors. A longitudinal study is underway. [Table: see text] No significant financial relationships to disclose.

13005 Background: Whilst oligodendroglial tumours are chemosensitive, the data about Temozolomide in high grade oligodendrogliomas are almost exclusively in recurrent tumours. Methods: 40 untreated patients of a planned 50 with high grade oligodendrogliomas were enrolled in a Phase II trial of Temozolomide. Eligible patients had confirmed oligodendrogliomas/astrocytomas and adequate organ function. Patients were excluded for prior chemotherapy or radiotherapy. Once recovered from surgery, patients were treated with 6 monthly cycles of Temozolomide (200 mg/m2 for five days), with post-chemotherapy radiotherapy at investigator discretion. Patients were assessed for loss of heterozygosity (LOH) of 1p and 19q, which are markers of chemosensitivity. The primary endpoint was disease-free progression at six months. Results: Patients were accrued within 42 months with 17 women (42.5%) and 37 (92.5%) having a performance status (ECOG) 0–2. Eight patients did not complete the full 6 cycles (6 progressed during chem...