Strike three for Novartis' canakinumab as lung cancer therapy

Expectations for Novartis' canakinumab as an oncology therapy were already fading fast, and have now been nixed after a third phase 3 trial in non-small cell lung cancer (NSCLC) failed to meet its objectives.

The latest disappointment comes from the CANOPY-A study in adults with stages II-IIIA and IIIB NSCLC, who were given canakinumab as adjuvant therapy after surgery to try to prevent the cancer from returning.

Treatment with the antibody was unable to show any improvement over placebo in disease-free survival (DFS), missing its primary endpoint.

Canakinumab is an anti-inflammatory drug targeting IL-1 beta that is already approved for diseases such as active systemic juvenile idiopathic arthritis under the brand name Ilaris.

Novartis was prompted to examine its potential in NSCLC on the back of the CANTOS trial reported in 2017, which found that patients treated with canakinumab in atherosclerotic disease appeared to have a reduced risk of lung cancer mortality.

Things started to go awry with the cancer programme in March 2021, when the phase 3 CANOPY-2 trial did not meet its aim of increasing overall survival (OS) when canakinumab was used as a second- or third-line therapy in NSCLC that had progressed despite prior chemo or immunotherapy.

Then, the following October, the CANOPY-1 study arrived at a similar conclusion, with  no improvement in OS or progression-free survival (PFS) when canakinumab was added to first-line therapy with Merck & Co's immunotherapy Keytruda (pembrolizumab) and platinum-based chemo.

CANOPY-A was Novartis' last throw of the dice for canakinumab as an NSCLC therapy, and was considered to have the best chance of showing an effect as its subjects more closely resembled the CANTOS population than the CANOPY-1 and 2 studies.

In a statement, the company said that it was disappointed by the outcome, but "every trial generates scientific evidence that supports future research and development."

At one point, analysts at Jefferies had suggested canakinumab could have potential of up to $2 billion in NSCLC, although they gave it a fairly low probability of approval.

Novartis is still running the phase 2 CANOPY-N study of neoadjuvant (pre-surgery) canakinumab in NSCLC, with a readout due in the coming days, according to its clinicaltrials.gov listing, but hopes for a positive outcome are now slim, and it is not expected to produce a result that would support a regulatory filing on its own.

The studies, at the very least, have helped Novartis explore the role of the so-called pro-tumour inflammation (PTI) pathway in oncology, which suggests inflammatory processes drive cancer development and suppress antitumour responses.

Novartis is developing other drugs that target the PTI pathway in cancer, including another IL-1 beta-targeting antibody, gevokizumab, which is in phase 1 testing with a lead indication of first-line colorectal cancer therapy.