Novartis Reports CANOPY-1 Phase III Failure for Canakinumab in NSCLC Despite Encouraging Subgroup Data at AACR 2022

Compiled by | Li Tom

Novartis' latest data from the CANOPY-1 Phase III trial, presented at the American Association for Cancer Research (AACR) Annual Meeting, showed that in newly diagnosed metastatic non-small cell lung cancer patients, canakinumab in combination with MSD’s Keytruda reduced the risk of death by 13% and the risk of disease progression or death by 17%. However, these improvements were not statistically significant. This trial marked the second failure of the inflammation drug canakinumab in NSCLC patient studies.

Despite this, Novartis remains optimistic that canakinumab monotherapy may eventually succeed as an adjuvant treatment option following surgery and chemotherapy for early-stage NSCLC. The drug is currently being studied in the CANOPY-A trial for this purpose. Novartis has stated that if approved for adjuvant treatment of non-small cell lung cancer, it could represent a sales peak for canakinumab potentially exceeding $1 billion.

Despite consecutive trial failures, Novartis remains confident in canakinumab primarily due to a predefined subgroup analysis based on the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP). Dr. Jeff Legos, Head of Global Oncology and Hematology Development at Novartis, explained that this biomarker is a recognized negative prognostic factor in most cancers. Novartis divided patients into four groups based on baseline hsCRP levels, and in the lowest quartile, canakinumab reduced the risk of death by 55% and the risk of disease progression or death by 43%.

In contrast, among patients with hsCRP levels in the highest quartile, little difference was observed between canakinumab recipients and those in the control group. Legos also highlighted that patients treated with canakinumab in the early stages of the CANOPY-A trial had lower hsCRP levels. Additionally, the CANTOS trial evaluated canakinumab as a secondary prevention measure for cardiovascular events in patients who had experienced a heart attack. The results showed that patients taking this drug had a significantly lower mortality rate from lung cancer.

It is reported that the CANOPY-A trial included patients in stages 2 to 3b, involving several subgroup analyses based on molecular alterations, PD-L1 expression, and hsCRP. The trial will also include some secondary endpoints measuring common symptoms in lung cancer patients. In the CANOPY-1 trial, treatment with canakinumab significantly reduced the risk of coughing, chest pain, and shortness of breath by 41%, 38%, and 33%, respectively.

Canakinumab is a human monoclonal antibody that selectively binds with high affinity to human interleukin-1β (IL-1β), neutralizing its activity by blocking its interaction with the receptor. In March of last year, in the Phase III CANOPY-2 clinical trial, canakinumab combined with docetaxel failed to meet the primary endpoint of improving OS in adult NSCLC patients who had previously received PD-1/PD-L1 inhibitors and platinum-based chemotherapy.

Notably, since Novartis launched the CANOPY-A trial in 2018, the market landscape for NSCLC adjuvant therapies has undergone significant changes. In October 2021, the U.S. FDA approved Roche's PD-L1 inhibitor Tecentriq in combination with chemotherapy as an adjuvant treatment for stage 2 to 3a NSCLC, requiring patients to have PD-L1 expression of at least 1%. Recent research from MSD also showed that, regardless of tumor PD-L1 expression status, using the PD-1 inhibitor Keytruda after surgery reduced the risk of disease recurrence or death by 24% in patients with stage 1b to 3a NSCLC. However, in the interim analysis, the benefit of Keytruda in patients with PD-L1 expression of 50% or higher did not reach statistical significance.

Reference Source: AACR: Novartis aims to keep canakinumab's early lung cancer hopes alive despite metastatic failure