Trial of Canakinumab in Previously Treated NSCLC Fails Primary End Point, Other Phase 3 Trials Remain Ongoing

Novartis’ investigational interleukin-1β inhibitor canakinumab plus docetaxel failed to show a survival benefit in patients with previously treated locally advanced or metastatic non–small cell lung cancer, but other trials examining its efficacy remain ongoing.

The phase 3 CANOPY-2 trial (NCT03626545) examining the interleukin-1β(IL-1β) inhibitor canakinumab (ACZ885) plus docetaxel in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with disease progressing on or after prior platinum-based chemotherapy and PD-1/L1 inhibitor therapy failed to meet its primary end point of overall survival (OS) superiority versus placebo, according to the drug’s developer Novartis.

Investigators on CANOPY-2 will analyze the findings from the trial and are expected to submit their research for presentation at an upcoming medical meeting.

“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,” John Tsai, MD, head of global drug development and chief medical officer at Novartis, said in a press release. “Ongoing phase 3 studies in non–small cell lung cancer continue evaluating canakinumab in earlier treatment settings. We sincerely thank the patients and clinical investigators involved in the CANOPY-2 study for their partnership.”

Other phase 3 trials of canakinumab across other NSCLC settings that remain ongoing include the CANOPY-1 trial (NCT03631199) of pembrolizumab (Keytruda) and platinum-based doublet chemotherapy with or without canakinumab in patients with previously untreated locally advanced or metastatic nonsquamous and squamous histology and the CANOPY-A trial (NCT03447769) examining the agent versus placebo as adjuvant therapy following complete resection of stage II, IIIA, and certain IIIB (T>5cm, N2 disease) tumors.

The ongoing CANOPY-1 study has enrolled 673 participants to assess the primary end points of OS and progression-free survival in the patient cohort receiving therapy in the frontline setting. To be eligible, patients must have had histologically confirmed stage IIIB or IV tumors, known PD-L1 status, an ECOG performance score of 0 or 1, and a least 1 measurable tumor by RECIST 1.1. CANOPY-A is actively recruiting, with a target enrollment of 1500 participants who have recovered from all toxicities related to prior systemic therapies and have an ECOG performance status of 0 or 1. The primary end point is disease-free survival.

Canakinumab is a humanized monoclonal antibody that binds selectively with IL-1β, interfering with its interaction with receptors. Early evidence suggested that this mechanism of action inhibits pro-tumor inflammation by enhancing antitumor response, reducing proliferation of tumor cells, and impairing angiogenesis.

Overall, the CANOPY study program was launched after lower rates of lung cancer mortality was observed in patients treated on the phase 3 cardiovascular CANTOS trial (NCT01327846), which looked at canakinumab as a secondary preventative therapy for events in patients who had experienced a myocardial infarction. Since the patient population in the trial was also at high risk for inflammatory cancers—due to advanced age, smoking history, and other clinical factors—investigators were able to determine an association with the agent and a lower incidence of lung cancer.2


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. Ridker PM, Thuren T, Zalewski A, et al. Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162(4):597-605. doi: 10.1016/j.ahj.2011.06.012