Canakinumab Combo Misses Survival End Points in Previously Untreated Locally Advanced or Metastatic NSCLC


Canakinumab plus pembrolizumab and platinum-based doublet chemotherapy did not significantly improve progression-free survival or overall survival in previously untreated patients with locally advanced or metastatic non–small cell lung cancer, missing the primary end points of the phase 3 CANOPY-1 trial.

John Tsai, MD

John Tsai, MD

Canakinumab (ACZ885) plus pembrolizumab (Keytruda) and platinum-based doublet chemotherapy did not significantly improve progression-free survival (PFS) or overall survival (OS) in previously untreated patients with locally advanced or metastatic non–small cell lung cancer (NSCLC), missing the primary end points of the phase 3 CANOPY-1 trial (NCT03631199).1

However, topline data also showcased potential clinically meaningful improvements in PFS and OS were with the regimen in prespecified patient subgroups based on the baseline inflammatory biomarker hs-CRP, as well as other biomarker-defined subsets.

As such, findings from the trial support further evaluation of the potential first-in-class interleukin (IL)-1β inhibitor of the PTI pathway, according to Novartis.

“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,” John Tsai, MD, head of Global Drug Development and chief medical officer at Novartis, stated 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.”

Canakinumab is a human monoclonal antibody that binds with high affinity and selectivity to IL-1β and was designed to neutralize IL-1β activity by blocking its interaction with its receptors. Preliminary data have indicated that the agent may inhibit PTI to strengthen antitumor immune responses, impair angiogenesis, and reduce tumor cell proliferation, survival, and invasiveness.

In the double-blind, randomized, placebo-controlled, 2-part phase 3 CANOPY-1 trial, investigators set out to evaluate the safety and efficacy of pembrolizumab plus platinum-based chemotherapy with or without canakinumab in previously untreated patients with stage IIIB/IIIC to IV squamous and nonsquamous NSCLC.2

The first part of the study, the open-label safety run-in portion, was comprised of 3 cohorts that enrolled approximately 9 patients each. These patients were given canakinumab at a subcutaneous dose of 200 mg every 3 weeks plus intravenous pembrolizumab at 200 mg every 3 weeks, and platinum-based chemotherapy.

Cohort A was comprised of patients with nonsquamous disease, who received carboplatin and pemetrexed as their chemotherapy. Cohort B also enrolled patients with nonsquamous disease, but these patients received cisplatin plus pemetrexed as their chemotherapy regimen. Lastly, cohort C included patients with either squamous or nonsquamous disease who received carboplatin and paclitaxel.

The second part of the trial enrolled approximately 600 patients, who were randomized 1:1 to receive canakinumab or placebo plus pembrolizumab and a platinum-based chemotherapy regimen. If patients had nonsquamous disease, they received carboplatin or cisplatin plus pemetrexed. If they had squamous disease, they were given carboplatin plus paclitaxel or nab-paclitaxel (Abraxane). Pemetrexed and platinum-based chemotherapy were administered at their approved doses.

Stratification factors included PD-L1 status, region, and histology.

In both parts of CANOPY-1, patients were given 4 cycles of induction therapy with canakinumab or placebo plus pembrolizumab and platinum-based chemotherapy followed by maintenance treatment with pembrolizumab plus canakinumab or placebo with or without paclitaxel until disease progression.

The primary objective of the first portion of the research was to determine the recommended phase 3 dose for the canakinumab combination. The primary goal for part 2 of the trial, was to evaluate the PFS and OS between the treatment arms. Secondary objectives for both parts of the trial included objective response rate, disease control rate, duration of response, safety, and pharmacokinetics.

CANOPY-1 is part of the CANOPY program, which was launched following the phase 3 CANTOS trial (NCT01327846), which examined canakinumab as a secondary prevention measure for cardiovascular events in patients after having experienced a heart attack. Patients enrolled to the trial were at high risk for inflammatory cancers such as lung cancer because of factors like age and smoking history, among others. Results from the trial showed that canakinumab resulted in raters of lung cancer mortality that were significantly lower than expected.

In addition to CANOPY-1, the double-blind, placebo-controlled, phase 3 CANOPY-A trial (NCT03447769) is examining canakinumab in the adjuvant setting after surgical resection and cisplatin-based chemotherapy. The primary objective of the research is to examine whether treatment with the agent will serve to prevent relapse.

The phase 2 neoadjuvant CANOPY-N trial (NCT03968419) is evaluating canakinumab either as a single agent or in combination with pembrolizumab in patients with resectable NSCLC before planned surgery.

Lastly, the double-blind, placebo-controlled, phase 3 CANOPY-2 trial (NCT03626545) is investigating the role of canakinumab plus docetaxel in second- or third-line treatment vs docetaxel alone in patients with NSCLC. However, data presented during the 2021 ESMO Congress showed that the addition of canakinumab did not improve OS or PFS in patients with advanced disease.3 Although the toxicity profiles proved to be similar between the treatment arms, a numerically higher incidence of infections was reported with canakinumab.

Novartis announced that they are collaborating with study investigators to produce further data analysis from CANOPY-1. Furthermore, the company announced plans to present the full dataset at an upcoming medical meeting.


  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. Tan DSW, Kim TM, Solomon BJ, et al. 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. Ann Oncol. 2019;30(suppl 9):IX179. doi:10.1093/annonc/mdz437.057
  3. Paz-Ares L, Goto Y, Lim WDT, et al. 1194MO canakinumab (CAN) + docetaxel (DTX) for the second- or third-line (2/3L) treatment of advanced non-small cell lung cancer (NSCLC): CANOPY-2 phase III results. Ann Oncol. 2021;32(suppl 5):S953-S954. doi:10.1016/j.annonc.2021.08.1799
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