Canopy-1: Phase 3 Study of Canakinumab/Placebo + Pembrolizumab + Platinum-chemotherapy in Untreated Stage III b-IV NSCLC pts

Background: Interleukin-1β (IL-1β) inhibition with canakinumab reduced the incidence of and mortality due to lung cancer among patients with atherosclerosis in CANTOS trial. Inhibition of IL-1β driven inflammation may lead to a tumor microenvironment more susceptible to anti-PD-(L)1 therapies. Recent studies have shown that low levels of CRP at baseline or decreased levels over time correlated with improved responses to anti-PD-(L)1 agents, providing rationale for combination of canakinumab and Pembrolizumab (PEM).

Method: CANOPY-1 (NCT03631199) is a double-blind, randomized, placebo (Pb)-controlled, phase III trial to determine efficacy and safety of PEM + platinum-based chemotherapy (Ctx) ± canakinumab in untreated stage IIIB/IIIC – IV squamous and non-squamous NSCLC pts. It is a 2 part study-In Part 1 [open-label safety run-in with 3 cohorts of ~ 9 pts each to confirm recommended phase 3 canakinumab regimen], pts will receive canakinumab 200 mg s.c. (Q3W) + PEM 200 mg i.v (Q3W) + platinum-based Ctx [Cohort A (non-squamous), carboplatin (CBCDA) + pemetrexed (PTX); Cohort B (non-squamous), cisplatin + PTX; Cohort C (squamous or non-squamous), CBCDA + paclitaxel]. In Part 2 [with ~ 600 pts) to evaluate efficacy and safety of canakinumab combination], pts will be randomized to receive canakinumab/Pb + PEM + platinum-based Ctx (non-squamous, CBCDA or cisplatin + PTX; squamous, CBCDA + paclitaxel or nab-paclitaxel). PEM and platinum-based Ctx will be administered at their approved doses. Randomization (1 : 1) will be stratified by PD-L1 status, region and histology. In both parts, pts will receive 4 cycles of induction therapy (canakinumab/Pb + PEM + Ctx) followed by maintenance therapy (PEM + canakinumab/Pb ± PTX) until progressive disease.

Primary objectives: confirm recommended phase 3 regimen for canakinumab combination (Part 1), compare PFS and OS between treatment arms (Part 2). Secondary objectives (Part 1 and 2): ORR, DCR, safety, PK and DOR.