South Korean pharmaceutical company Hanmi Pharmaceutical has announced promising results from a Phase I/II clinical trial evaluating the combination of Tivumecirnon with MSD's Keytruda (pembrolizumab) in patients with advanced or metastatic gastric cancer.
The study, conducted in partnership with MSD and RAPT Therapeutics, demonstrated marked efficacy differences based on patients' Epstein-Barr virus (EBV) status, potentially identifying a key biomarker for treatment response.
Clinical Trial Results
In the trial's stratified analysis, researchers observed striking differences between EBV-positive and EBV-negative cohorts. Among the ten EBV-positive patients, the combination therapy achieved a 60% objective response rate, with five patients showing partial responses and one achieving a complete response. In contrast, the ten EBV-negative patients showed no objective responses.
The EBV-positive group demonstrated robust efficacy metrics, with a median time to response of 2.7 months and a median duration of response extending to 17.3 months. Notably, the median progression-free survival reached 10.4 months in this cohort.
Safety and Tolerability Profile
Safety analysis across all 20 participants revealed a favorable profile for the combination therapy. Treatment-related adverse events were generally manageable, with no new safety signals identified during the study period.
Mechanism of Action and Development History
Tivumecirnon represents an innovative approach to cancer immunotherapy as an oral C-C chemokine receptor 4 (CCR4) antagonist. The drug works by blocking the CCR4 receptor protein, which typically enables regulatory T cell migration into tumors, suppressing immune responses against cancer cells.
The development of Tivumecirnon stems from a collaborative effort initiated in 2019 when RAPT Therapeutics introduced the compound to Hanmi Pharmaceutical. The program expanded in 2020 through a clinical collaboration agreement with MSD.
Expert Perspective
Dr. Do-Youn Oh, professor of hematology and oncology at Seoul National University Hospital and principal investigator of the study, emphasized the significance of the findings: "Tivumecirnon in combination with Keytruda demonstrated significant antitumor effects in patients with EBV-positive gastric cancer. The high objective response rate and sustained duration of response highlight new possibilities for cancer immunotherapy."
Dr. Oh further noted that these results underscore the innovative potential of CCR4 receptor-targeted therapies in advancing cancer treatment options.
