532TiP - CANOPY-1: A phase III, placebo-controlled study of pembrolizumab (PEM) plus platinum-based doublet chemotherapy (Ctx) with/without canakinumab in untreated patients (pts) with stage IIIB/IIIC-IV NSCLC

Background

Interleukin-1β (IL-1β) inhibition with canakinumab was associated with a significant reduction in the incidence of lung cancer and lung cancer mortality in pts 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 combining canakinumab and PEM.

Trial design

CANOPY-1 (NCT03631199) is a double-blind, randomized, placebo (Pb)-controlled, phase III trial to determine efficacy and safety of PEM + platinum-based 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), pts received 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), pts will be randomize 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 (RP3R) 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. Part 1 is completed and part 2 is ongoing based on the confirmation of canakinumab 200 mg Q3W + PEM and platinum-doublet Ctx as RP3R.

Clinical trial identification

CACZ885U2301/NCT03631199.

Editorial acknowledgement

Legal entity responsible for the study

Novartis.

Funding

Novartis.

Disclosure

D.S.W. Tan: Advisory / Consultancy: Novartis, Pfizer, AstraZeneca; Research grant / Funding (self): Novartis ; Advisory / Consultancy: Novartis; Research grant / Funding (self): Pfizer, AstraZeneca. T.M. Kim: Advisory / Consultancy: AstraZeneca, Novartis, Takeda, Sanofi, and Bayer ; Research grant / Funding (self): AstraZeneca-KHIDI outside this work. B.J. Solomon: Advisory / Consultancy: Roche/Genentech; AstraZeneca; Novartis; Pfizer; Merck; Bristol-Myers Squibb; Loxo Oncology; Gritstone Oncology; Honoraria (self): Roche/Genentech; AstraZeneca; Novartis; Pfizer; Merck; Bristol-Myers Squibb; Loxo Oncology; Gritstone Oncology. W.L. Tan: Travel / Accommodation / Expenses: Boehringer Ingelheim for WCLC in Toronto Sept 2018 . S. Geater: Honoraria (self): AstraZeneca, Boehringer Ingelheim, Roche; Advisory / Consultancy: Boehringer Ingelheim; Research grant / Funding (institution): AstraZeneca, Boehringer Ingelheim, Roche, MSD; Travel / Accommodation / Expenses: AstraZeneca, Boehringer Ingelheim, Roche. G. De Castro Jr.: Honoraria (self): Bristol-Myers Squibb; Merck Serono Serbia; MSD; Advisory / Consultancy: Bristol-Myers Squibb; MSD; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Merck Serono Serbia; MSD; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Merck Serono Serbia; MSD. A. Greystoke: Speaker Bureau / Expert testimony: Novartis, AstraZeneca, Boehringer Ingelheim, BMS, MSD, Takeda, Pfizer; Advisory / Consultancy: Novartis, AstraZeneca, Boehringer Ingelheim, BMS, MSD, Takeda, Pfizer. E. Felip: Advisory / Consultancy: AbbVie; AstraZeneca; Blueprint Medicines; Boehringer Ingelheim; Bristol-Myers Squibb; Celgene; Guardant Health; Lilly; Merck KGaA; Merck Sharp & Dohme; Novartis; Pfizer; Roche; Takeda; Speaker Bureau / Expert testimony: AbbVie; AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Lilly; Merck KGaA; Merck Sharp & Dohme; Novartis; Pfizer; Roche; Takeda; Research grant / Funding (self): EMD Serono (Inst); Fundación Merck Salud (Inst). B.E. Johnson: Advisory / Consultancy: Novartis Steering Committee and Array Biopharma Steering Committee; Research grant / Funding (self): Research Grants from Novartis and Cannon Medical Imaging. A-L. Louveau: Full / Part-time employment: Novartis. V.Q. Passos: Full / Part-time employment: Novartis. B.C. Cho: Shareholder / Stockholder / Stock options: TheraCanVac Inc; Honoraria (self): AstraZeneca; Bayer; Champions Oncology; Dizal Pharma; Dong-A ST; Janssen; MOGAM Institute; MSD; Novartis; Ono Pharmaceutical; Yuhan; Advisory / Consultancy: AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Janssen; Lilly; MSD; Novartis; Ono Pharmaceutical; Pfizer; Roche; Takeda; Yuhan; Speaker Bureau / Expert testimony: Novartis; Research grant / Funding (self): AstraZeneca; Bayer; Champions Oncology; Dizal Pharma; Dong-A ST; Janssen; MOGAM Institute; MSD; Novartis; Ono Pharmaceutical; Yuhan; Licensing / Royalties: Champions Oncology. All other authors have declared no conflicts of interest.