Canakinumab Plus Chemotherapy Show No OS Improvement in Advanced or Metastatic NSCLC

Results from the phase CANOPY-2 clinical trial of canakinumab in combination with docetaxel as treatment of advanced or metastatic non–small cell lung cancer did not yield a favorable survival outcome.

The combination of canakinumab, an interleukin-1beta (IL-1β) inhibitor, and docetaxel chemotherapy did not show improvement in overall survival (OS) in adult patients with previously treated locally advanced or metastatic non–small cell lung cancer (NSCLC), missing the primary end point of the phase 3 CANOPY-2 clinical trial (NCT03626545), according to a press release from Novartis.1

“While results from the CANOPY-2 trial are not what we hoped for in patients with advanced or metastatic non-small cell lung cancer who have been treated with other lines of therapy, these data give us valuable insights into IL-1β inhibition,” said John Tsai, MD, head of Global Drug Development and chief medical officer, Novartis, in a statement.

CANOPY-2 is an ongoing randomized, double-blind, placebo-controlled study, which is evaluating the efficacy and safety of canakinumab plus docetaxel in 245 patients with locally advanced or metastatic NSCLC who were previously treated with PD-1/PD-L1 inhibitors and platinum-based chemotherapy. In addition to OS, the study also explored the coprimary end point of the incidence of dose-limiting toxicities (DLTs) in an earlier safety run-in phase of the study. The secondary end points of CANOPY-02 include objective response rate, duration of response, and disease control rate for all study patients. In randomized patients, the additional key secondary end points are progression-free survival and time to response.

The trial is no longer recruiting patients. Those eligible for enrollment were patients with histologically confirmed disease who were previously treated with PD-L1 inhibitors and platinum-based chemotherapy who have an ECOG performance status of 0 or 1 and at least 1 measurable lesion. Those excluded from the study were patients who were previously treated with docetaxel, canakinumab, or another systemic therapy locally advanced or metastatic NSCLC other than an anti–PD-L1 agent or platinum-based chemotherapy; EGFR- or ALK-positive tumors; and severe hypersensitivity reaction to monoclonal antibodies, taxanes, or excipients of docetaxel or canakinumab.

The data from the study are being analyzed by investigators and will be presented during an upcoming medical meeting.

CANOPY-2 is part of a clinical trial program launched by Novartis to develop canakinumab in various settings of NSCLC. Canakinumab works by selectively connecting to human IL-1β and balances activity by blocking its interaction with human IL-1β receptors. Preliminary data have shown that based on the mechanism of action of canakinumab, the agent has the ability to promote anti-tumor immune response, reduce tumor cell proliferation, survival or tumors, and tumor invasiveness, as well as diminish angiogenesis.

In the CANOPY program, 2 clinical trials remain in positive standing. One ongoing study is the phase 3 CANOPY-1 trial of canakinumab plus pembrolizumab (Keytruda) as treatment of patients with advanced or metastatic NSCLC (NCT03631199). In the earlier phase 2 portion of CANOPY-1, a tolerable safety profile was observed with canakinumab plus pembrolizumab in a cohort of 30 patients.2

None of the serious adverse events (AEs) that occurred were fatal or considered to be canakinumab-related. Three patients in the study discontinued treatment as a result of AEs. The development of hepatitis led to the discontinuation of pembrolizumab in the study, and polyneuropathy and peripheral neuropathy led to the discontinuation of chemotherapy.

Only one DLT was observed during the safety run-in analysis of CANOPY-1, which was grade 3 hepatitis that occurred within the first 42 days of therapy. The case was found to be related to treatment with pembrolizumab.

Overall, the most common grade 3 AEs observed were pulmonary embolism in (10%) and decreased neutrophil count (10%). A grade 4 AE of cardiac tamponade occurred in 1 patient. There was one death reported, which was considered disease related.

The second trial ongoing in the CANOPY program is the phase 3 CANOPY-A trial, which is investigating the use of canakinumab as adjuvant therapy for patients with completely resected NSCLC (NCT03447769). The latest information from the trial shows that more than 950 patients have been enrolled. The target enrollment for the study is 1500 patients.1


1. Novartis provides update on phase III study evaluating canakinumab (ACZ885) as second or third-line treatment in combination with chemotherapy in non-small cell lung cancer. News release. Novartis. March 9, 2021. Accessed March 9, 2021.

2. Johnson BE, Kim TM, Hiltermann JN, et al. CANOPY-1: Safety run-in results from phase (ph) 3 study of canakinumab (CAN) or placebo (PBO) in combination (comb) with pembrolizumab (PEM) plus platinum-based doublet chemotherapy (Ctx) as 1st line therapy in patients (pts) with advanced or metastatic NSCLC. Presented at: 2020 American Association for Cancer Research Virtual Annual Meeting I; April 27-28, 2020; Virtual. Abstract CT214.