Abstract C100: Safety run-in results from phase 3 study of canakinumab (CAN) or placebo in combination with pembrolizumab (PEM) plus platinum-based doublet chemotherapy (Ctx) as 1st line therapy in patients (pts) with advanced or metastatic NSCLC (CANOPY-1)

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. Results of phase 3 CANTOS study have shown that IL-1β inhibition with CAN was associated with reduced incidence of lung cancer and lung cancer mortality, thus providing a rationale to investigate therapeutic role of CAN in lung cancer. CANOPY-1 (NCT03631199) is a placebo-controlled, double-blind, randomized, phase 3 trial designed to evaluate efficacy and safety of PEM + Ctx ± CAN in previously untreated 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 non-randomized, safety run-in part where pts received CAN 200 mg s.c Q3W + PEM 200 mg i.v Q3W + platinum-based Ctx [Cohort A (non-squamous), carboplatin + pemetrexed; Cohort B (non-squamous), cisplatin + pemetrexed; Cohort C (squamous or non-squamous), carboplatin + paclitaxel]. Part 2 of the study randomizes pts to evaluate efficacy and safety of CAN combination regimen vs placebo combination regimen. Primary objective of safety run-in part: RP3R for CAN in combination with PEM + Ctx. 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 cohort A (A), 11 pts in cohort B (B), and 9 pts in cohort C (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 (5 pts; 3 pts in A and 1 pt each in B and C) and 1 patient died due to study indication. Dose-limiting toxicity (DLT) occurring during first 42 days of study tx was reported only in 1 pt (cohort C: grade 3 hepatitis, not related to CAN). Recommended phase 3 regimen (RP3R) of CAN in combination with standard dose of PEM + Ctx was confirmed as 200 mg SC Q3W based on Bayesian logistic regression model (BLRM). Serious AEs regardless of study drug relationship were reported in 8 (27%) pts (2 pts in A and 3 pts each in B and C), none of which 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%). Overall, 14 pts (47%) experienced grade 3 AEs and 1 pt experienced grade 4 AE (cardiac tamponade unrelated to study drugs). 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 this triplet combination of CAN + PEM + Ctx. Based on BLRM and all relevant data, the RP3R of CAN as 200 mg SC Q3W combination was considered safe and well tolerated. Enrolment is ongoing in randomized phase 3 part of study to evaluate efficacy and safety. 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, Enriqueta Felip, Alastair Greystoke, Benjamin J. Solomon, Noelia Nebot, Stephanie Deudon, Anne-Laure Louveau, Vanessa Q. Passos, Daniel SW Tan. Safety run-in results from phase 3 study of canakinumab (CAN) or placebo in combination with pembrolizumab (PEM) plus platinum-based doublet chemotherapy (Ctx) as 1st line therapy in patients (pts) with advanced or metastatic NSCLC (CANOPY-1) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C100. doi:10.1158/1535-7163.TARG-19-C100