Zev A. Wainberg

Zev Wainberg is a leading clinician-scientist specializing in upper GI malignancies — gastric cancer, gastroesophageal junction (GEJ) cancer, esophageal cancer, and biliary tract cancers — with a particular focus on HER2-directed therapeutics and novel molecular targets. As Co-Director of the UCLA GI Oncology Program, he has been at the forefront of transforming gastric/GEJ cancer therapy through precision medicine and novel antibody-based approaches. HER2 overexpression or amplification occurs in approximately 15–20% of gastric and GEJ adenocarcinomas and has been a major therapeutic target since trastuzumab demonstrated a survival benefit in HER2-positive advanced gastric cancer in the ToGA trial. Wainberg has been a central investigator in expanding HER2-targeted strategies beyond trastuzumab. He served as a principal investigator for the MOUNTAINEER trial, a phase II study that evaluated tucatinib — a highly selective HER2 tyrosine kinase inhibitor — in combination with trastuzumab in patients with HER2-positive, previously treated metastatic colorectal and gastric/GEJ cancers. In gastric/GEJ cancer, the MOUNTAINEER results demonstrated clinically meaningful activity in a heavily pretreated population and supported the development of tucatinib-based combinations in this setting. Wainberg has also been a pivotal investigator in the clinical development of zolbetuximab, a first-in-class monoclonal antibody targeting Claudin 18.2 (CLDN18.2) — a tight junction protein aberrantly expressed in approximately 40% of gastric/GEJ adenocarcinomas. He contributed to the SPOTLIGHT and GLOW phase III trials, which demonstrated that adding zolbetuximab to FOLFOX or CAPOX chemotherapy significantly improved progression-free survival and overall survival in CLDN18.2-positive, HER2-negative gastric/GEJ cancer. These results led to FDA approval of zolbetuximab in 2024 and validated CLDN18.2 as an important actionable target in gastric oncology. Beyond gastric cancer, Wainberg's research encompasses antibody-drug conjugates (ADCs) in GI malignancies, tumor microenvironment characterization, and combinatorial immunotherapy strategies. He has led multiple investigator-initiated trials combining checkpoint inhibitors with novel targeted agents and plays a key role in shaping next-generation clinical trials for upper GI malignancies.

Zev Wainberg 是专注于上消化道恶性肿瘤的领先临床科学家，特别关注HER2靶向治疗和新型分子靶点。他是UCLA胃肠肿瘤项目联合主任。 Wainberg 是MOUNTAINEER试验的主要研究者，评估了tucatinib联合曲妥珠单抗在HER2阳性胃癌/GEJ癌中的活性。他还参与了SPOTLIGHT和GLOW III期试验，这些试验验证了zolbetuximab（靶向CLDN18.2的单克隆抗体）联合化疗在CLDN18.2阳性、HER2阴性胃/GEJ腺癌中的显著疗效，推动了FDA于2024年批准zolbetuximab。