Canakinumab With Pembrolizumab Shows No Significant Survival Benefit for Locally Advanced or Metastatic NSCLC

The phase CANOPY-1 study has missed its co primary end points, but signals observed in a non–small cell lung cancer subgroup warrant further investigation.

The investigational combination of canakinumab plus pembrolizumab (Keytruda) did not achieve a statistically significant improvement in progression-free survival (PFS) or overall survival (OS) in patients with locally advanced or metastatic non-squamous and squamous non–small cell lung cancer (NSCLC) compared with placebo, missing the coprimary end points of the phase 3 CANOPY-1 clinical trial, according to a press release issued by Novartis.1

It was noted, however, that in the pre-specified subgroups of patients with high-sensitivity C-reactive protein, a clinically meaningful improvement in both PFS and OS was observed, indicating a need for further evaluation of canakinumab in patients with lung cancer. Data analyses are ongoing in the study and full results will be presented during an upcoming medical meeting.

“CANOPY-1 provides critical insights into the treatment of this devastating disease, and we will continue to analyze the data and conclusions, as well as their potential clinical implications,” said John Tsai, MD, head of Global Drug Development and chief medical officer, Novartis, in a press release. “While this trial did not confirm the benefit for all patients we hoped for, we are energized by the overall CANOPY-1 findings as they support our commitment to continue studying canakinumab in lung cancer.

CANOPY-1 is a randomized, double-blind, placebo-controlled, phase 3 trial of 673 patients with locally advanced or metastatic non-squamous and squamous NSCLC.

In the experimental treatment arm, patients received canakinumab in combination with pembrolizumab 200 mg and with platinum-bases doublet chemotherapy. Options for chemotherapy in the study included carboplatin AUC 5 mg/mL or AUC 6 mg/mL, cisplatin 75 mg/m2, paclitaxel 200 mg/m2, nab-paclitaxel 100 mg/m2, or pemetrexed 500 mg/m2. All therapies in the study were administered every 3 weeks. In the comparator treatment arm, patients received matching placebo and platinum-based doublet chemotherapy.2

The study began with a safety run-in portion during which the primary end point of incidence of dose-limiting toxicity (DLT) was evaluated. Results reported in 2020 showed that the combination of canakinumab and pembrolizumab was safe with minimal DLTs. The analysis included 30 patients who has with previously untreated stage IIIB or IIIC or stage IV NSCLC. Six patients discontinued treatment, 1 patient died, and 24 remained on treatment.3,4

There were no serious adverse events (AEs) that led to death or that were considered to be related to canakinumab.

In the later portion of the study, the coprimary end points of PFS at the 18-month mark and OS at 38 months were evaluated by investigator assessment per RECIST v1.1. The key secondary end points of the study were ORR, disease control rate, duration of response, time to response, and other efficacy end points.2

To be included in the study, patients were required to have histologically confirmed local advanced stage IIIB or stage IV NSCLC for treatment in the first-line setting, and have positive PD-L1 expression, an ECOG performance status of 0 or 1, and at least 1 measurable lesion per RECIST v1.1

The study excluded patients who previously received immunotherapy, canakinumab, or another study drug along with those who had an EGFR mutation, central nervous system involvement, leptomeningeal disease, or infections that may compromise their immunity.

Canakinumab, a human monoclonal antibody, can achieve anti-tumor response, reduce tumor cell proliferation, prolong survival, improve tumor invasiveness, and impair angiogenesis by bind to human interleukin-1beta to block interaction with its receptors. Study of the agent is ongoing in the CANOPY clinical trial program, which includes patients with early-stage and advanced lung cancers.1


1. Novartis top-line results for CANOPY-1 Phase III study support further evaluation of canakinumab in lung cancer. News release. Novartis. October 25, 2021. Accessed October 25, 2021.

2. Study of efficacy and safety of pembrolizumab plus platinum-based doublet chemotherapy with or without canakinumab in previously untreated locally advanced or metastatic non-squamous and squamous nsclc subjects (CANOPY-1). Accessed October 25, 2021.

3. Zhou Q, Wu Y-L, et al. Efficacy and safety of pralsetinib in Chinese patients with advanced RET fusion+ non-small cell lung cancer. Presented at: 2021 World Conference on Lung Cancer; September 8-14, 2021; virtual. Abstract M02.02.

4. Lu S, Cheng Y, Huang D, et al. Efficacy and safety of selpercatinib in Chinese patients with RET fusion-positive non-small cell lung cancer: a phase 2 trial. Presented at: International Association for the Study of Lung 2021 World Conference on Lung Cancer; September 8-14, 2021; virtual. Abstract MA02.01.