Transcenta Updates Efficacy Data from Osemitamab Triple Combo Trial for G/GEJ Cancer at ESMO 2024

Updated results from the TranStar102 study have been released, showcasing the efficacy of Osemitamab (TST001) in combination with Nivolumab and CAPOX as a first-line treatment for advanced gastric and gastroesophageal junction (G/GEJ) cancer. This announcement was made by Transcenta Holding Limited, a global clinical-stage biopharmaceutical company specializing in antibody-based therapeutics.

The latest findings indicate 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 expression of CLDN18.2 and known PD-L1 status. Most of these patients exhibited a PD-L1 combined positive score (CPS) of less than 5.

In a comparative analysis, those with very low or no CLDN18.2 expression were used as a control group. The hazard ratio (HR) for the triple combination therapy favored the CLDN18.2 high/medium expression group at 0.505 (95% CI, 0.244-1.045). These findings support the synergistic mechanism between the CLDN18.2 targeting agent and checkpoint inhibitors, as previously reported by Transcenta. The CLDN18.2 targeting antibody has been shown to induce PD-L1 expression in gastric cancer tumor cells, even in cases with low or null PD-L1 expression. Additionally, the treatment prompts T-cell infiltration.

At the cutoff date, the median overall survival (OS) had not been reached due to the limited number of events. However, the 12-month survival rate for the 82 patients in this cohort was recorded at 73.8% (95% CI: 62.0-82.4%).

Previous research has indicated that combining Zolbetuximab with CAPOX in CLDN18.2 positive patients, irrespective of PD-L1 status, results in an improvement in PFS from 6.80 to 8.21 months (HR = 0.687, 95% CI, 0.544-0.866). The current Cohort-G data reveals that the triple therapy of Osemitamab, Nivolumab, and CAPOX demonstrates substantially better efficacy compared to historical data of either Nivolumab plus CAPOX or Zolbetuximab plus CAPOX combinations.

The new data was highlighted in a poster presentation at the ESMO Congress 2024 in Barcelona, Spain. Dr. Caroline Germa, Executive Vice President of Global Medicine Development and Chief Medical Officer at Transcenta, commented on the significance of these results. She noted that the confirmed ORR and mPFS in patients with high or medium CLDN18.2 expression, compared to those with no CLDN18.2 expression, underline the synergy between Osemitamab and checkpoint inhibitors. This demonstrates the potential of the triple combination therapy, even in patients with low PD-L1 expression.

Professor Lin Shen, Director of the Department of Gastrointestinal Oncology and the Phase I Clinical Trial Center at Peking University Cancer Hospital, also emphasized the clinical benefits of the triple combination therapy. He pointed out the significant improvement in PFS and ORR, particularly in patients with high or medium CLDN18.2 expression and low PD-L1 CPS, suggesting a promising therapeutic approach.

The TranStar102 study's Cohort G explored the safety and efficacy of Osemitamab plus Nivolumab and CAPOX as a first-line treatment for advanced G/GEJ cancer. The study included a safety lead-in and expansion phase, with patients allocated to receive either 3 or 6 mg/kg at the expansion phase. Eligible patients were those with HER2-negative or unknown, unresectable locally advanced or metastatic G/GEJ cancer, regardless of CLDN18.2 or PD-L1 expression. The expressions of CLDN18.2 and PD-L1 were retrospectively analyzed.

As of the cut-off date, 82 patients had received treatment with a median follow-up of 15.2 months. The mPFS varied among different expression levels of CLDN18.2, with the highest mPFS observed in patients with high or medium expression. The safety profile was deemed manageable, with common adverse events including hypoalbuminaemia, nausea, and vomiting, mostly of grade 1 or 2 severity.

Osemitamab is a high-affinity humanized anti-CLDN18.2 monoclonal antibody, designed to enhance antibody-dependent cellular cytotoxicity (ADCC). It has shown potent anti-tumor activity in preclinical models. Osemitamab is currently undergoing clinical trials in the U.S. and China and has received Orphan Drug Designation from the FDA for treating gastric, gastroesophageal junction, and pancreatic cancers.