Calithera Biosciences Inc. (NASDAQ:CALA) has announced the dosing of the first patient in its randomized second phases non-small cell lung cancer glutaminase inhibitor telaglenastat (CB-839) study in combination with carboplatin, pemetrexed, and pembrolizumab.
KEAPSAKE Study to evaluate the safety and antitumor activity of CB-839
The company will evaluate the antitumor activity and safety of telaglenastat in the KEEPSAKE study. They will evaluate CB-839 in combination with standard-of-care immunotherapy as first-line therapy to treat stage IV non-squamous NSCLC patients with NRF2 or KEAP1 mutation tumors. The KEAP1/NRF2 mutations pathway occurs in around 20% of patients with NSCLC, and they are linked with aggressive tumor growth.
Recently Calithera presented clinical results that demonstrated that the activation of the KEAP1/NRF2 pathway was related to poor clinical outcomes in NSCLC patients receiving first-line chemoimmunotherapy. The activation was either through NRF2 activation or KEAP1 function loss. According to preclinical studies, the activation of NRF2/KEAP1 pathway leads to reliance on glutaminase activity for both growth and survival and thus makes the tumors exquisitely sensitive to glutaminase activity inhibition through telaglenastat.
KEAPSAKE trial among first studies investigating NSCLC therapy
Susan Molineux, the CEO, and president of Calithera stated that therapies inhibiting glutaminase in tumors with NRF2/KEAP1 pathway activation will have a significant clinical impact on patients with NSCLC. She added that the company is delighted to commence the KEAPSAKE trial, which is among the first studies investigating a potential novel therapy for NSCLC patients who tend to have a poor prognosis. Molineux said that based on the strong preclinical data and the clear mechanistic approach for telaglenstat in NSCLC, they are optimistic that the clinical trials will yield valuable insights.
The company will enroll around 120 stage IV non-squamous NSCLC patients with KEAP1/NRF2 mutation tumors in the double blind KEAPSAKE study. The subjects will be randomized to receive telaglenstats or placebo plus standard-of-care carboplatin, pemetrexed, and pembrolizumab. This study will evaluate the safety and progression-free survival of telaglenastat in combination with standard of care chemoimmunotherapy regimen. The company is expecting to share the preliminary results from the KEAPSAKE study by next year.