China-based biotech Transcenta Holdings Ltd (HKG: 6628) announced interim safety and efficacy data from a Phase I/II study of TST001 (osemitamab), a humanized ADCC-enhanced anti-Claudin18.2 monoclonal antibody (mAb), in combination with capecitabine and oxaliplatin (CAPOX) as a first-line treatment for locally advanced or metastatic gastric or gastroesophageal junction (GC/GEJ) cancer. The data from the dose expansion cohort was presented at the European Society for Medical Oncology (ESMO) Congress 2022.
Positive Trial Results
As of August 4, 2022, 51 patients were enrolled and dosed, including 36 patients treated with TST001 plus CAPOX at 6mg/kg Q3W in the expansion phase (median follow-up of 65 days). Among the 15 patients with measurable disease and at least one post-treatment tumor assessment, 11 (73.3%) achieved partial response, and four (26.7%) achieved stable disease as the best overall tumor response per RECIST1.1, resulting in a disease control rate of 100%. Six out of the eight patients with medium or high Claudin 18.2 expression, and all five patients with unknown Claudin 18.2 expression achieved a partial response.
Safety and Tolerability
All 51 enrolled patients were evaluated for safety and tolerability. Treatment-emergent adverse events (TEAEs) regardless of causality were mostly grade 1-2, including nausea, hypoalbuminemia, anemia, vomiting, and decreased platelet count. Twelve (23.5%) patients experienced dose delay, five (9.8%) experienced dose reduction, and no patient experienced discontinuation due to treatment-related adverse events (TRAEs).
Previous Study Results
Previously, Transcenta published the results of a Phase I dosage escalation study for TST001 combined with CAPOX in first-line advanced and metastatic gastric cancer/carcinoma of gastroesophageal junction (GC/GEJC) at the ASCO 2022 annual meeting in June. As of April 5, 2022, 14 patients received 1, 3, 6, or 8 mg/kg every 3 weeks in the dose escalation phase. Twelve patients received TST001 combined with CAPOX at a dose of 6 mg/kg every 3 weeks during the expansion phase. The data showed that the combination was well tolerated as a first-line treatment for patients with advanced and metastatic gastric cancer/gastroesophageal junction cancer, with encouraging preliminary antitumor activity observed.
About TST001
TST001 is a high-affinity humanized anti-Claudin18.2 mAb with enhanced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities, demonstrating potent anti-tumor activities in tumor xenograft models. The drug, generated using Transcenta’s Immune Tolerance Breaking Technology (IMTB) platform, is the second most advanced Claudin18.2 targeting antibody being developed globally. Clinical trials for TST001 (Osemitamab) are ongoing in the US and China (NCT04396821, NCT04495296/CTR20201281). TST001 (Osemitamab) was granted Orphan Drug Designation status in the US by the FDA for the treatment of patients with gastric or gastroesophageal junction (G/GEJ) cancer.-Fineline Info & Tech
