Canakinumab Fails to Meet DFS End Point in Resected NSCLC

The anti–interleukin-1β monoclonal antibody canakinumab (ACZ885) did not generate a disease-free survival (DFS) benefit vs placebo in adult patients with stages II to IIIA and IIIB (T > 5 cm; N2 disease) completely resected non–small cell lung cancer (NSCLC), failing to meet the primary end point of the phase 3 CANOPY-A trial (NCT03447769).¹

No new safety signals were observed. Full data from the trial will be presented at an upcoming medical meeting.

“We made an investment in the CANOPY program based on signals of reduced lung cancer incidence and mortality observed in the CANTOS study. These positive signals supported the study of canakinumab as adjuvant treatment for early lung cancer,” Jeff Legos, executive vice president and global head of Oncology & Hematology Development at Novartis, stated in a news release. “While we are disappointed CANOPY-A did not show the benefit we hoped for, every trial generates scientific evidence that supports future research and development, and we look forward to continuing to pursue new therapeutic options for people living with lung cancer, whose needs remain urgent and significant. We thank the patients and clinical investigators whose time and commitment made this research possible.”

Canakinumab binds with high affinity and selectivity to human IL-1β, inhibiting IL-1β activity by blocking its interaction with its receptors. Preliminary evidence pointed to canakinumab suppressing tumor inflammation to enhance antitumor immune response, impair angiogenesis, and reduce tumor cell proliferation, survival, and invasiveness.

CANOPY-A is part of the CANOPY program that launched following the phase 3 CANTOS trial (NCT01327846), which examined canakinumab as a secondary prevention measure for cardiovascular events in patients following who had a heart attack. CANTOS enrolled patients who were at high risk for inflammatory cancers such as lung cancer because of factors like age and smoking history, and findings led to the investigation of canakinumab as a treatment for NSCLC in the phase 3 CANOPY-A, CANOPY-1 (NCT03631199), and CANOPY-2 (NCT03626545) trials, plus the phase 2 CANOPY-N trial (NCT03968419).

The CANOPY-A study evaluated canakinumab in the adjuvant setting after surgical resection and cisplatin-based chemotherapy. The trial enrolled patients with stage IIA to IIIA and IIIB (N2 disease only) who underwent complete resection or were candidates for complete resection. Patients also needed to have recovered to grade 1 or less from all toxicities related to prior systemic therapy, except for any-grade alopecia and grade 2 or lower neuropathy. An ECOG performance status of 0 or 1 was required.²

Patients with unresectable or metastatic disease, positive microscopic margins on the pathology report, and/or gross disease remaining at the time of surgery, were excluded. Any prior neoadjuvant therapy was not permitted. Standard-of-care adjuvant cisplatin-based chemotherapy and radiation was required to be completed prior to randomization.

The trial enrolled 1382 patients who were randomized to receive 200 mg of subcutaneous canakinumab or matching placebo every 3 weeks for up to 1 year. The primary end point of the trial was DFS by local investigator. Secondary end points included overall survival (OS) in the overall population, PD-L1, and CD8 subgroups; DFS in PD-L1 and CD8 subgroups; lung cancer–specific survival; pharmacokinetics; and safety.

Previously reported data from the CANOPY-2 trial showed that canakinumab plus docetaxel failed to significantly improve OS in patients with locally advanced or metastatic NSCLC whose disease had progressed while on, or after, prior platinum-based chemotherapy and a PD-L1 agent, missing the primary end point of that study.³

Additionally, canakinumab plus pembrolizumab (Keytruda) and platinum-based doublet chemotherapy did not significantly improve progression-free survival or OS in previously untreated patients with locally advanced or metastatic NSCLC, missing the primary end points of the CANOPY-1 trial.⁴

References

1. Novartis provides update on phase III CANOPY-A study evaluating canakinumab as adjuvant treatment in non-small cell lung cancer. News release. Novartis. August 15, 2022. Accessed August 15, 2022. https://bit.ly/3JYGDTO
2. Study of efficacy and safety of canakinumab as adjuvant therapy in adult subjects with stages AJCC/UICC v. 8 II-IIIA and IIIB (T>5cm N2) completely resected non-small cell lung cancer acronym: CANOPY-A. ClinicalTrials.gov. Updated July 27, 2022. Accessed August 15, 2022. https://clinicaltrials.gov/ct2/show/NCT03447769
3. 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. March 9, 2021. Accessed August 15, 2022. http://bit.ly/3l1AvgI
4. 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 August 15, 2022. https://bit.ly/3pyfhvt