Zymeworks announces new, updated zanidatamab data at ASCO

Zymeworks announced new and updated clinical data for the HER2-targeted bispecific antibody zanidatamab, in both HER2-expressing biliary tract cancer, or BTC, and gastroesophageal adenocarcinoma, or GEA. The data are being presented at the American Society of Clinical Oncology, or ASCO, Gastrointestinal Cancers Symposium, taking place virtually January 15-17. HER2 is overexpressed in approximately 20% of GEA patients. For these patients, trastuzumab in combination with chemotherapy is the only approved HER2-targeted therapy. Treatment options are currently limited if disease progression occurs after trastuzumab in combination with chemotherapy. Findings from an ongoing Phase 1 study of zanidatamab in HER2-positive GEA were last presented in July 2020. The data being reported are from HER2-expressing GEA patients who received zanidatamab either as monotherapy or in combination with chemotherapies. The groups had a median of two to three prior therapies, with a high percentage having received prior HER2-targeted therapies. The data continue to demonstrate that zanidatamab is well tolerated with the majority of treatment-related AEs considered mild to moderate in severity and manageable in the outpatient setting. In 33 response-evaluable patients who received zanidatamab as monotherapy, the objective response rate, or ORR, was 39%, 11 of which were confirmed by a subsequent scan. The disease control rate, or DCR, was 61% and median duration of response (DOR) was six months. In 10 response-evaluable patients who received zanidatamab plus paclitaxel, the ORR was 60%, five of which were confirmed by a subsequent scan including one patient who experienced a complete response. The DCR was 90% (9/10) for this group. In 14 response-evaluable patients who received zanidatamab plus capecitabine, the confirmed ORR was 57% and the DCR was 71%. Overall the median DOR for zanidatamab plus chemotherapy was 8.9 months and the median progression-free survival, or PFS, was 5.6 months with eight patients still on study at the time of data cut-off. Zanidatamab in HER2-positive biliary tract cancers: Results from a Phase 1 study. Findings from the ongoing Phase 1 study of zanidatamab in HER2-amplified BTC were last shared in July 2020. The updated and new results are being presented in a poster session at the ASCO Gastrointestinal Cancers Symposium. Data were reported on 21 patients diagnosed with HER2-amplified BTC who received zanidatamab at the recommended dose of 20 mg/kg every two weeks. Patients received a median of two prior therapies and five of the patients were previously treated with the HER2-targeted therapy trastuzumab. Zanidatamab was well tolerated and demonstrated durable antitumor activity in these patients. All zanidatamab-related adverse events, or AEs, were mild or moderate in severity. The confirmed ORR, in trastuzumab-naive patients was 47% and overall ORR was 40%. The overall disease control rate, or DCR, was 65% and median duration of response, or DOR, was 7.4 months with several patients still on study at the time of data cut-off. Zymeworks is presenting a trial in progress poster at ASCO GI for a global pivotal Phase 2 trial in HER2-amplified BTC. Multiple clinical sites are now open to enrollment in the U.S., South Korea, Italy and Spain, with additional sites planned in Canada, Chile, China, France and the UK. This study is designed to support accelerated approval based on a primary endpoint of objective response rate, and key secondary endpoints of duration of response and safety.