Abstract CT214: CANOPY-1: Safety run-in results from phase (ph) 3 study of canakinumab (CAN) or placebo (PBO) in combination (comb) with pembrolizumab (PEM) plus platinum-based doublet chemotherapy (Ctx) as 1stline therapy in patients (pts) with advanced or metastatic NSCLC

Cytokine interleukin-1β (IL-1β) has multiple pro-tumorogenic effects on tumor microenvironment, thereby promoting carcinogenesis, tumor invasiveness, and immunosuppression. CAN is a selective IL-1β inhibitor that aims to target tumor-promoting inflammation to reduce immune suppression, thereby potentiating effects of immunotherapy with PD-1 inhibitors such as PEM. Ph 3 CANTOS study has shown IL-1β inhibition with CAN was associated with reduced incidence of lung cancer (LC) and LC mortality in pts with atherosclerosis, providing a rationale to investigate therapeutic role of CAN in LC. CANOPY-1 (NCT03631199) is a PBO-controlled, double-blind, randomized, ph 3 trial designed to evaluate efficacy and safety of PEM + Ctx ± CAN in tx naive pts with stage IIIB/IIIC (not eligible for definitive chemo-radiation curative tx) or stage IV squamous and nonsquamous NSCLC. The study was divided into 2 parts: part 1 is open labelled, safety run-in part where pts received CAN 200 mg s.c Q3W + PEM 200 mg i.v Q3W + platinum-based Ctx (as induction during first 4 cycles only); Cohort A (A, non-squamous), carboplatin + pemetrexed; Cohort B (B, non-squamous), cisplatin + pemetrexed; Cohort C (C, squamous or non-squamous), carboplatin + paclitaxel. Part 2 is randomized and evaluates efficacy and safety of CAN comb regimen vs PBO comb regimen. Primary objective of safety run-in part: recommended ph 3 dose regimen (RP3R) of CAN comb. Secondary objectives: ORR, DCR, DOR, safety, PK, and immunogenicity. As of 14 May 2019 (follow-up of ≥42 days from C1D1 unless pt discontinued earlier), 10 pts in A, 11 pts in B, and 9 pts in C were treated, of which 73% were male, median age was 63 yrs. In total, 24/30 (80%) pts enrolled were still receiving tx; primary reason for tx discontinuation was progressive disease (3 pts in A and 1 pt each in B and C) and 1 pt died due to study indication. 1 pt reported DLT during first 42 days of study tx (C: grade 3 hepatitis, not related to CAN). RP3R of CAN in comb with standard dose PEM + Ctx was 200 mg SC Q3W based on Bayesian logistic regression model (BLRM). Serious AEs regardless of causality were reported in 8 (27%) pts (2 pts in A and 3 pts each in B and C), none of which were considered to be related to CAN. Most common AEs (≥20%, any grade) across all cohorts (n=30) were nausea (37%), vomiting (30%), constipation and fatigue (each 23%), and neutrophil count decrease (20%). 14 pts (47%) experienced grade 3 AEs and 1 pt experienced grade 4 AE (cardiac tamponade [unrelated]). No fatal serious AEs were reported. AEs leading to discontinuation of one of the study drugs were reported in 3 (10%) pts (hepatitis, peripheral neuropathy, and polyneuropathy) but none were CAN related. AEs leading to dose reduction and dose interruption of one of study drugs were reported in 3 (10%) pts and 5 (17%) pts, respectively. Only 1 DLT was reported with CAN + PEM + Ctx. Based on BLRM and all relevant clinical data, the RP3R of CAN as 200 mg SC Q3W comb was considered safe and well tolerated. Enrollment for the randomized part is completed. Citation Format: Bruce E. Johnson, Tae Min Kim, T. Jeroen N. Hiltermann, Fabrice Barlesi, Christian Grohe, Yasushi Goto, Orvar Gunnarsson, Tobias Overbeck, Noemi Reguart, Martin Wermke, Gilberto Castro Castro, Enriqueta Felip, Alastair Greystoke, Benjamin J. Solomon, Stephanie Deudon, Anne-Laure Louveau, Vanessa Passos, Daniel SW Tan. CANOPY-1: Safety run-in results from phase (ph) 3 study of canakinumab (CAN) or placebo (PBO) in combination (comb) with pembrolizumab (PEM) plus platinum-based doublet chemotherapy (Ctx) as 1st line therapy in patients (pts) with advanced or metastatic NSCLC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT214.