No abstract

NI combination therapy. Of the 5 patients who derived clinical benefit (defined as best response of PR, or ongoing PR/SD at 6 months), 4 were T790M negative. Incidence of pneumonitis was 3.2% (n¼1, G1). Other toxicities include IDDM (n¼1), polymyositis (n¼1), hypothyroidism (n¼2), transaminitis (n¼1) and rash (n¼5). There were no G3-5 toxicities. We next interrogated the immune landscape of EGFR TKI resistant NSCLC, and examined the impact of ipilumumab-nivolumab. 4/23 (17.4%) baseline samples were GEP high (2/4 were T790M positive), with enrichment for exhausted CD8, Treg and overexpression of IDO1. Of these 4 patients, 2 derived clinical benefit to N monotherapy. In sequential biopsies before and after exposure to checkpoint inhibitors, increase in infiltrating CD8 T cells was associated with clinical benefit. Conclusion: While there were no significant toxicity concerns with combination checkpoint inhibition in TKI-resistant EGFR mutant NSCLC, durable response was not demonstrated in our study. High GEP alone did not seem to predict for response to checkpoint inhibitors in EGFR mutant NSCLC, possibly due an immunosuppressive tumor microenvironment.

1864 patients were enrolled to be screened, of whom NGS was available for 1672. 73% of the sequenced tumor samples were archival and 27% were fresh biopsies; there were no significant differences in prevalence of genetic alterations between these. MEGSA identified two non-overlapping sets of mutually exclusive gene alterations with a false discovery rate (FDR) < 15%: NFE2L2, KEAP1 and PARP4 (FDR ¼ 4.1%) and CDKN2A and RB1 (FDR ¼ 13.1%). Mutual exclusivity of NFE2L2 and KEAP1 alterations has been previously observed, e.g., in TCGA, however mutual exclusivity of PARP4 and NFE2L2 or KEAP1 alterations is a novel finding. SELECT identified 41 pairs of mutually exclusive and 95 pairs of co-occurring gene alterations. Top significant co-occurring pairs that appeared in this dataset but not TCGA include CDKN2A and TP53, KRAS and STK11, HGF and MLL2, PDGFRB and SMARCA4, NFE2L2 and TP53, ATRX and RUNX1T1, GRIN2A and NCOR1, and MCL1 and MYCN. Male sex and smoking history were associated with poorer survival. When these and other clinical covariates were incorporated in Cox proportional hazards models, there were no individual genetic variants that were associated with survival; however, NFE2L2 and KEAP1 alterations when taken together were associated with poorer survival. Conclusion: This analysis of the Lung-MAP S1400 NGS data features a substantially larger sample size than any previously published dataset of squamous cell lung cancers, although it is limited to genes sequenced on the FoundationOne T5 platform. Compared to TCGA, this dataset features a homogeneous set of subjects all with previously treated advanced disease and enrolled on a clinical trial. Novel findings, including mutual exclusivity of PARP4 and NFE2L2 or KEAP1 alterations, suggest that PARP4 may have a hitherto undiscovered role in a key pathway known to impact responses to oxidative stress and treatment resistance.

survival (OS) respectively. Secondary endpoints include objective response rates, local and distant disease control, and quality of life/ patient reported outcomes assessment. Translational science component includes blood and tissue based immune related assays. Results: This study activated in May 2019. 120 of 506 planned patients have been accrued as of 8/20/2020.

Background:Inhibitors of CTLA-4 and PD-1 have shown improvements in survival in multiple advanced cancers. Immune-mediated effects such as arthralgias and arthritis have been described, but their prevalence and characteristics have not been well defined.Objectives:The objective of the study is to describe the prevalence of immunomediated joint manifestations (IJM), its characteristics and evolution in patients who received immunotherapy (nivolumab (NV), pembrolizumab (PB)) from January 1, 2016 to December 31, 2018 in our center.Methods:Data collection was performed at through the RPT (Registre Pacients Tractats) database of the CatSalut, and the patients referred to the monographic medical office of inflammatory joint diseases of our center. In all cases, the variables: age, sex, neoplasia, drug, number of doses, were recorded. In patients with joint involvement: other autoimmune manifestations, joint affectation prior to treatment, delay rheumatology derivation, joint affectation type, swollen and tender joint counts, ESR, CRP, RF, ACPA, ANA, HLA B 27, Hb, leukocytes, neutrophils, lymphocytes, treatment and evolution, were recorded. The statistical analysis was carried out with the SPSS 15.0 computer packageResults:106 patients received treatment (TTO) with immunotherapy (71 NV, 35 BP) for neoplasia (81 lung, 10 renal, 8 melanoma, 2 oropharynx). The mean age was 67.93 ± 10.7 years (21.7% women, 78.3% men). There were 11 events cataloged as IJM. The overall prevalence was 10.3% (5.6% NV, 14.3% PB). Patients with IJM received a greater number of doses (17.67 ± 9.3 vs9.24 ± 10.1 p = 0.018). No patient with melanoma presented IJM. All IJM suspicions cases were assessed by a rheumatology. When studying their characteristics (Table 1), 3 patients were added from the database of the rheumatology service (14 cases). They received in a clinical trial BP29541 (rectal cancer), Atezolizumab (lung cancer) and Durvalumab (lung cancer). 42.9% of the patients presented inflammatory arthralgias (IAT) and 57.1% arthritis (AT). In reference to their previous history, 2 patients had a history of hyperuricemia and arthritis. One patient concomitantly presented lymphocytic colitis confirmed by biopsy. The delay time for assessment by rheumatology was 18.1 ± 22.1 days. Patients with AT were older (p = 0.014), had higher ESR (p = 0.047) than those with IAT. No differences were found in other variables (table1). With reference to the analytical study, 1 patient was RF +, 2 ANA + at mean titers (1/160-1/320), none ACPA or HLA B 27 +. After assessment by rheumatology, two patients with IAT were diagnosed with bone M1 and two AT were categorized as gouty arthritis. The rest of the IAT responded to NSAIDs, did not require corticosteroids and were resolved. 6 cases of AT received prednisone, 3 required treatment dose 1 mg/kg weight and subsequently MTX in 2 of them, with evolution to low disease activity at present. Only one patient met RA classification criteria.Conclusion:The prevalence of IJM was higher than 10%, depending on the number of...