bemcentinib + carboplatin + pembrolizumab + pemetrexed

The combination therapy bemcentinib + carboplatin + pembrolizumab + pemetrexed is being investigated for the treatment of advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). This is a multi-drug regimen currently in clinical trials, specifically in Phase 1b/2a studies. ## Mechanism and Components This combination therapy consists of four distinct agents: 1. **Bemcentinib (BEM)**: A targeted therapy that inhibits AXL, a protein involved in cancer growth and progression. 2. **Pembrolizumab**: An immune checkpoint inhibitor that enhances the immune system's ability to detect and fight cancer cells. 3. **Carboplatin**: A platinum-based chemotherapy drug that damages the DNA of cancer cells, preventing them from dividing. 4. **Pemetrexed**: An anti-folate chemotherapy agent that disrupts processes necessary for cancer cell replication. ## Clinical Development The combination is being studied in a Phase 1b/2a clinical trial (NCT05469178) for patients with advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC without actionable mutations. The trial has a particular focus on patients with STK11 mutations. In the study protocol, patients receive bemcentinib orally once daily along with standard chemo-immunotherapy. After 4 cycles of the complete combination, maintenance therapy with bemcentinib + pemetrexed + pembrolizumab continues for up to 2 years. The Phase 1b portion follows a 3+3 design exploring three bemcentinib dose levels (75mg, 100mg, and 150mg), while the Phase 2a expansion will enroll up to 40 patients with STK11 mutations. ## Safety and Efficacy While specific results for this exact four-drug combination aren't yet available, the pembrolizumab + pemetrexed + carboplatin combination (without bemcentinib) has shown efficacy in real-world settings with median progression-free survival of 9.0 months and overall survival of 20.6 months for patients with advanced non-squamous NSCLC. A related study of pembrolizumab + pemetrexed in elderly patients with metastatic non-squamous NSCLC showed an objective response rate of 36.7%, with a median progression-free survival of 7.6 months and median overall survival of 19.4 months. The addition of bemcentinib to this established regimen aims to potentially improve outcomes, particularly for patients with STK11 mutations who typically respond poorly to standard therapies.

Other names

BGB324 + MK-3475 + pemetrexed + carboplatin