Novartis' canakinumab in NSCLC phase 3 trial failed again 2022 AACR

Novartis' latest data from the CANOPY-1 Phase 3 trial presented at the American Association for Cancer Research (AACR) annual meeting show that in patients with newly diagnosed metastatic non-small cell lung cancer, canakinumab monoclonal antibody combined with Merck's Keytruda reduces the risk of death13 %, a 17% lower risk of disease progression or death
.
However, these improvements were not statistically significant, and the trial is the second time the inflammatory disease drug canakinumab has failed in a trial of NSCLC patients
.
Nonetheless, Novartis remains optimistic that canakinumab monotherapy may eventually succeed as an adjuvant treatment option after surgery and chemotherapy in early-stage NSCLC, and the drug is currently being studied in the CANOPY-A trial
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Novartis has said that if approved for the adjuvant treatment of non-small cell lung cancer, it could represent peak sales of canakinumab of more than $1 billion
.
In the face of successive trial failures, Novartis remains confident in canakinumab mainly based on a predefined subgroup analysis of the high-sensitivity C-reactive protein (hsCRP) inflammatory marker
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The marker is a well-recognized negative prognostic factor for most cancers, explained Jeff Legos, PhD, head of global oncology and hematology development at Novartis
.
Novartis divided patients into four groups based on baseline hsCRP levels, and in the lowest quartile, canakinumab was able to reduce the risk of death by 55% and the risk of disease progression or death by 43%
.
In contrast, for patients with hsCRP levels in the highest quartile, little difference was observed between canakinumab and control patients
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Legos also highlighted that patients who received canakinumab in the early stages of the CANOPY-A trial had lower levels of hsCRP
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In addition, the CANTOS trial evaluated canakinumab as secondary prevention of cardiovascular events in patients with heart attack
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It was found that lung cancer mortality was much lower in patients taking the drug
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The CANOPY-A trial included patients in stages 2 to 3b and included several subgroup analyses based on molecular alterations, PD-L1 expression, and hsCRP
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The trial will also include secondary endpoints that measure some of the common symptoms in lung cancer patients
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In the CANOPY-1 trial, canakinumab treatment significantly reduced the risk of cough, chest pain and shortness of breath by 41%, 38% and 33%, respectively
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Canakinumab is a human monoclonal antibody that selectively binds to human interleukin-1β (IL-1β) with high affinity and neutralizes the activity of IL-1β by blocking its interaction with the receptor
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In March last year, canakinumab monoclonal antibody combined with docetaxel was used in the phase III CANOPY-2 clinical trial for the treatment of adult NSCLC patients who had previously received PD1/PDL1 inhibitors and platinum-based chemotherapy.
The trial failed to meet the primary endpoint of improving OS
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It is worth noting that since Novartis advanced the CANOPY-A trial in 2018, the market landscape of adjuvant therapy for NSCLC has changed dramatically
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In October 2021, the US FDA approved the Roche PD-L1 inhibitor Tecentriq combined with chemotherapy as an adjuvant treatment for stage 2 to 3a NSCLC, and requires patients to have at least 1% PD-L1 expression
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A recent study by Merck also showed that the use of the PD-1 inhibitor Keytruda after surgery reduced the risk of disease recurrence or death by 24% in a population of stage 1b to 3a NSCLC patients, regardless of tumor PD-L1 expression status
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However, at the interim analysis, the benefit of Keytruda in patients with high PD-L1 expression of 50% and above did not reach statistical significance
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Reference source: AACR: Novartis aims to keep canakinumabs early lung cancer hopes alive despite metastatic failure