The FDA has given clearance for a pivotal gastric cancer Phase III trial.
Osemitamab (TST001) offers hope for patients with HER2-negative gastric or gastroesophageal adenocarcinoma, a disease with limited treatment options and poor survival rates. By specifically targeting CLDN18.2, combining it with Nivolumab and chemotherapy, and leveraging the enhanced ADCC properties of Osemitamab, it aims to reshape the treatment paradigm for G/GEJ cancer.
With over one million new cases reported in 2020 alone, gastric cancer is ranked fifth in incidence among all cancers globally. This disease also ranks fourth in mortality with an estimated 769,000 deaths. This makes it the cause of one in every 13 deaths around the world.
Current treatment options for HER2-negative advanced gastric cancer often involve combinations of platinum and fluoropyrimidine chemotherapy. While these regimens have shown improvements in treatment outcomes, the median survival remains less than 14 months.
PHASE III TRIAL
Osemitamab (TST001) represents a second-generation humanized antibody that specifically targets CLDN18.2. CLDN18.2 is a protein expressed in gastric and gastroesophageal adenocarcinomas. By targeting CLDN18.2, Osemitamab aims to reshape the treatment paradigm for G/GEJ cancer.
This innovative therapy not only binds to CLDN18.2 better, but also exhibits enhanced antibody-dependent cellular cytotoxicity (ADCC). Meaning, Osemitamab has the ability to induce immune cells to selectively kill CLDN18.2-expressing tumor cells, leading to potential anti-tumor effects.
Background on Phase II Trial
To support the global Phase III trial application, Transcenta has conducted Phase II clinical trials in both the United States and China. These trials evaluated the combination of Osemitamab with chemotherapy or nivolumab and chemotherapy. Various doses of Osemitamab were administered to optimize the dosage for the upcoming Phase III trial.
Encouraging efficacy data from these Phase II trials were presented at the 2023 ASCO annual meeting and the 2023 ESMO GI conference. In a dose escalation and dose expansion cohort, 64 patients were enrolled and treated with Osemitamab. Doses ranged from 1 to 8 mg/kg Q3W. The results showed that the estimated median progression-free survival (PFS) was 9.5 months for all dose groups, regardless of CLDN18.2 expression levels. The median duration of response (DOR) was 9.9 months.
Furthermore, it was found that CLDN18.2 positivity, defined as IHC membrane staining of ≥10% tumor cells with ≥1+ intensity per LDT assay, was required for the efficacy expansion. This data suggests that more than 55% of all G/GEJ adenocarcinomas could potentially benefit from the addition of Osemitamab to the standard of care.
The specific PFS and DOR data for the 49 patients treated at the dose of 6 mg/kg Q3W in the efficacy expansion will be presented at ESMO 2023. This presentation will provide further insights into the effectiveness of this innovative therapy.
Moving Forward
In addition to the FDA clearance for the global Phase III pivotal trial, the Center for Drug Evaluation (CDE) in China and MFDS in South Korea have also granted approvals for the Phase III trial. This signifies the international recognition and potential impact of Osemitamab on the treatment landscape for HER2-negative metastatic gastric or gastroesophageal adenocarcinoma.
To support the Phase III trial application and FDA End-of-Phase 2 (EOP2) meeting, Transcenta has collaborated with a credible companion diagnostic (CDx) developer in the United States to develop a CLDN18.2-specific diagnostic assay. This assay will aid in identifying patients who are likely to benefit from Osemitamab treatment, further optimizing patient selection for this therapy.
For more information on gastroesophageal adenocarcinoma and other rare cancers visit, checkrare.com/diseases/cancers/
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