A phase II, open label study of tucatinib (ONT-380) combined with trastuzumab in patients with HER2+ metastatic colorectal cancer (mCRC)(MOUNTAINEER).

作者：John H. Strickler, Donna Niedzwiecki, Tyler Zemla, Andrea Cercek, Marwan Fakih, Kimmie Ng, Federico Augusto Sanchez, Christina Wu, Scott Peterson, Lorelei A. Bandel, Axel Grothey, Tanios Bekaii‐Saab · 发表于：Journal of Clinical Oncology · 年份：2017 · DOI：10.1200/jco.2017.35.15_suppl.tps3624 · 被引用次数：16 · 研究领域：Colorectal Cancer Treatments and Studies、HER2/EGFR in Cancer Research、Gastric Cancer Management and Outcomes

TPS3624 Background: To improve survival for patients with mCRC, efforts are needed to identify and treat actionable genomic alterations. HER2 is amplified in approximately 5-8% of patients with KRAS and NRAS (RAS) wild-type mCRC. HER2 functions as an oncogenic driver and a mediator of EGFR antibody (Ab) resistance. Although prior studies have shown that anti-HER2 therapies are active in patients with HER2+ (HER2 IHC 3+ or HER2 amplified) mCRC, there are no HER2-directed therapies approved for these patients. Tucatinib is a potent and highly selective oral small molecule tyrosine kinase inhibitor of HER2, currently being developed to treat metastatic breast cancer. In HER2+ CRC patient derived xenograft models, tucatinib has substantial anti-tumor activity. The addition of the anti-HER2 monoclonal Ab trastuzumab augments tumor growth inhibition. Methods: This single-arm phase II study will test the combination of tucatinib and trastuzumab in patients with HER2+ mCRC. Eligible patients include those with RAS wild-type mCRC who have been previously treated with 5-FU, oxaliplatin, irinotecan, and an anti-VEGF monoclonal Ab. Patients must have HER2+ disease by IHC, FISH, or NGS. Prior treatment with anti-HER2 targeting therapy is excluded. The primary objective is to assess the objective response rate for the combination. Secondary objectives are to evaluate the efficacy (PFS, OS, clinical benefit rate), safety, and tolerability of the combination. Correlation between tissue and b...