Updated results from the cohort-G data of the TranStar102 study indicate that Osemitamab (TST001) combined with Nivolumab and CAPOX as a first-line treatment shows encouraging efficacy for patients with advanced gastric or gastroesophageal junction (G/GEJ) cancer. The data, presented at the ESMO Congress 2024, highlights a confirmed objective response rate (ORR) of 68% and a median progression-free survival (mPFS) of 14.2 months in patients with high or medium CLDN18.2 expression and known PD-L1 status (n=66).
The study, a cohort of the Transtar102 trial (NCT04495296), was designed to evaluate the safety and efficacy of Osemitamab (TST001) plus Nivolumab and CAPOX as a first-line treatment for advanced G/GEJ cancer. The trial included a safety lead-in and expansion phase, with patients alternately allocated to 3 or 6mg/kg during the expansion phase. Eligible patients included those with HER2 negative or unknown, unresectable locally advanced or metastatic G/GEJ cancer, regardless of CLDN18.2 or PD-L1 expression.
Efficacy Outcomes
As of the data cut-off, 82 patients had been dosed with a median follow-up of 15.2 months. In the overall patient group, the mPFS was 12.6 months in patients with high or medium CLDN18.2 expression, 7.1 months in patients with low expression, and 8.5 months in the rest of the patients. The confirmed ORR was 58.1%, 52.4%, and 55.6%, respectively. The 12-month survival rate for the overall population was 73.8% (95% CI: 62.0-82.4%).
In the subgroup of patients with known CLDN18.2/PD-L1 status (n=66), the mPFS was 14.2 months in patients with high or medium CLDN18.2 expression, 8.5 months in patients with low expression, and 6.7 months in the rest of the patients. The confirmed ORR was 68.0%, 61.1%, and 50.0%, respectively.
For the subgroup with PD-L1 CPS<5 (n=56), the mPFS was 16.6 months in patients with high or medium CLDN18.2 expression, 7.1 months in patients with low expression, and 5.7 months in the rest of the patients. The confirmed ORR was 71.4%, 60.0%, and 47.1%, respectively.
Safety Profile
The safety profile was manageable, with all patients experiencing treatment-related adverse events (TRAEs). The most common TRAEs were hypoalbuminaemia, nausea, and vomiting, most of which were of CTC AE grade 1 or 2.
Mechanism of Action
Osemitamab (TST001) is a high-affinity humanized anti-CLDN18.2 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC). It has demonstrated potent anti-tumor activities in tumor xenograft models. The updated data corroborates the synergistic mechanism of action between CLDN18.2 targeting agent and checkpoint inhibitors, showing that CLDN18.2 targeting antibody can induce PD-L1 expression in gastric cancer tumor cells and T-cell infiltration.
Expert Commentary
"The updated data from the Cohort-G trial of Osemitamab (TST001) in combination with Nivolumab and CAPOX as first-line treatment for advanced G/GEJ cancer are highly encouraging," said Dr. Caroline Germa, Executive Vice President, Global Medicine Development and Chief Medical Officer at Transcenta. "The confirmed objective response rate and median progression-free survival in patients with high/medium CLDN18.2 expression, known PD-L1, as compared to patients with no CLDN18.2 expression, confirm the synergy between Osemitamab (TST001) and Checkpoint inhibitors and demonstrates the potential of this triple combination therapy, potentially including in low PD-L1 expressers."
Professor Lin Shen, Director, Department of Gastrointestinal Oncology and Phase I Clinical Trial Center at Peking University Cancer Hospital and Principal Investigator of the trial, added, "The Cohort-G data presented at ESMO 2024 provide compelling evidence of the clinical benefit of the triple combination therapy. The significant improvement in progression-free survival and objective response rate, particularly in patients with high/medium CLDN18.2 expression and low PD-L1 CPS, is a testament to the potential of this therapeutic approach."
