Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study

• Published in: The Lancet Oncology
• Main Authors: Strickler, John H, Cercek, Andrea, Siena, Salvatore, André, Thierry, Ng, Kimmie, Van Cutsem, Eric, Wu, Christina, Paulson, Andrew S, Hubbard, Joleen M, Coveler, Andrew L, Fountzilas, Christos, Kardosh, Adel, Kasi, Pashtoon M, Lenz, Heinz-Josef, Ciombor, Kristen K, Elez, Elena, Bajor, David L, Cremolini, Chiara, Sanchez, Federico, Stecher, Michael, Feng, Wentao, Bekaii-Saab, Tanios S
• Format: Text
• Language: unknown
• Published: Advocate Aurora Health Institutional Repository 2023
• Subjects: Chemotherapy; Tucatinib; trastuzumab; metastatic colorectal cancer; MOUNTAINEER; Advocate Aurora Research Institute; Oncology; Aurora Research Institute
• Online Access: https://institutionalrepository.aah.org/allother/518; https://doi.org/10.1016/S1470-2045(23)00150-X; https://libkey.io/libraries/1712/10.1016/S1470-2045(23)00150-X

Background: HER2 is an actionable target in metastatic colorectal cancer. We assessed the activity of tucatinib plus trastuzumab in patients with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer. Methods: MOUNTAINEER is a global, open-label, phase 2 study that enrolled patients aged 18 years and older with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer at 34 sites (clinics and hospitals) in five countries (Belgium, France, Italy, Spain, and the USA). Initially, the study was designed as a single-cohort study, which was expanded following an interim analysis to include more patients. Initially, patients were given tucatinib (300 mg orally twice daily) plus intravenous trastuzumab (8 mg/kg as an initial loading dose, then 6 mg/kg every 21 days; cohort A) for the duration of treatment (until progression), and after expansion, patients were randomly assigned (4:3), using an interactive web response system and stratified by primary tumour location, to either tucatinib plus trastuzumab (cohort B) or tucatinib monotherapy (cohort C). The primary endpoint was confirmed objective response rate per blinded independent central review (BICR) for cohorts A and B combined and was assessed in patients in the full analysis set (ie, patients with HER2-positive disease who received at least one dose of study treatment). Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT03043313 , and is ongoing. Findings: Between Aug 8, 2017, and Sept 22, 2021, 117 patients were enrolled (45 in cohort A, 41 in cohort B, and 31 in cohort C), of whom 114 patients had locally assessed HER2-positive disease and received treatment (45 in cohort A, 39 in cohort B, and 30 in cohort C; full analysis set), and 116 patients received at least one dose of study treatment (45 in cohort A, 41 in cohort B, and 30 in cohort C; safety population). In the full analysis set, ...