Seattle Genetics initiates phase III trial ( HER2CLIMB-02) of tucatinib + ado-trastuzumab emtansine to treat metastatic HER2-positive (HER2+) breast cancer.

Seattle Genetics, Inc. announced dosing of the first patient in HER2CLIMB-02, a randomized phase III clinical trial evaluating investigational agent tucatinib versus placebo, in combination with standard-of-care ado-trastuzumab emtansine (T-DM1, Kadcyla), for patients with locally advanced or metastatic HER2-positive (HER2+) breast cancer. This trial is intended to support registration in the U.S. Tucatinib is an oral, small molecule tyrosine kinase inhibitor that is highly selective for HER2.

HER2CLIMB-02 is a multi-center, randomized, double-blind, placebo-controlled phase III trial designed to evaluate tucatinib versus placebo, in combination with T-DM1, in patients with unresectable locally-advanced or metastatic HER2+ breast cancer, including those with brain metastases, who have had prior treatment with a taxane and trastuzumab in any setting. The primary endpoint is progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints include overall survival, objective response rate and duration of response. The trial is expected to enroll approximately 460 patients. More information about this phase III trial, including enrolling centers, is available at www.clinicaltrials.gov. HER2CLIMB-02 is based on the results from a completed phase 1b study. The manuscript entitled �Tucatinib combined with ado-trastuzumab emtansine in advanced ERBB2/HER2-positive metastatic breast cancer: The results of a phase 1b trial� evaluating tucatinib with the current standard of care HER2-targeted antibody-drug conjugate, T-DM1, in previously treated metastatic HER2-positive breast cancer was published in the July 2018 print edition of JAMA Oncology.

See-"Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2 -Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial"-Virginia F. Borges, MD, MMSc; Cristiano Ferrario, MD; Nathalie Aucoin, MD; JAMA Oncol. 2018; 4(9):1214-1220. doi: 10.1001/jamaoncol.2018.1812.

Tucatinib is being evaluated in an ongoing randomized, double-blind, placebo-controlled pivotal trial called HER2CLIMB comparing tucatinib vs. placebo, in combination with capecitabine and trastuzumab in patients with pretreated, unresectable, locally advanced or metastatic HER2-positive breast cancer, including patients with or without brain metastases. In addition, tucatinib is being evaluated in other solid tumor clinical trials, including colorectal cancer.