Phase 2 Success: Tivumecirnon Combo in Advanced HNSCC Post-CPI Therapy

RAPT Therapeutics, a company specializing in immunology-based therapeutics, has reported positive results from a Phase 2 clinical trial combining tivumecirnon, an oral small molecule CCR4 antagonist, with pembrolizumab, an anti-PD-1 checkpoint inhibitor, for the treatment of advanced head and neck squamous cell carcinoma (HNSCC). The trial focused on patients whose cancer had progressed after previous treatment with checkpoint inhibitors. The data, presented at the AACR Annual Meeting, showed a confirmed objective response rate (ORR) of 15.6% across all patients, regardless of PD-L1 or HPV status. Notably, the ORR was 17.4% in patients with PD-L1+ disease and 22.2% in those with HPV+ disease. The median duration of treatment for responders was 19.6 months.
The study included 32 patients with heavily pretreated HNSCC, with nearly 70% having received three to six prior treatments. The observed ORRs were significantly higher than the expected rate for anti-PD-1 monotherapy in similar patients, which is less than 5-10%. Tivumecirnon has been well-tolerated in over 350 patients with various cancers, either as a single agent or in combination with pembrolizumab, with no increased immune-related toxicity signals.
Brian Wong, President and CEO of RAPT, expressed optimism about the potential of tivumecirnon, which is also being evaluated for its efficacy in non-small cell lung cancer, gastric cancer, and non-Hodgkin lymphoma. The ongoing open-label Phase 1/2 study is enrolling patients with multiple cancer types across the U.S., Australia, and Asia, with the Phase 2 portion specifically assessing tivumecirnon's antitumor activity in Treg and CCR4 pathway-enriched tumors.
Tivumecirnon is designed to inhibit the migration of regulatory T cells into tumors, potentially enhancing the body's natural antitumor immunity and complementing various cancer treatments. RAPT Therapeutics is developing selective small molecules to target critical immune pathways in inflammatory diseases and cancer, with two drug candidates, zelnecirnon and tivumecirnon, targeting CCR4 for inflammation and cancer treatment, respectively. The company is also exploring other targets in the early stages of development.