Tucatinib plus trastuzumab for chemotherapy-refractory, HER2 + , RAS wild-type metastatic colorectal cancer (MOUNTAINEER): final analysis
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: MOUNTAINEER was a multicenter, open-label, phase 2 trial (NCT03043313) that evaluated the efficacy and safety of tucatinib plus trastuzumab, a dual HER2-targeted chemotherapy-free regimen. Patients were included if they had chemotherapy-refractory, HER2+, RAS wild-type unresectable or metastatic colorectal cancer. This final analysis reports updated efficacy and safety after a median follow-up of 32.4 months. Of the 84 patients who received tucatinib plus trastuzumab, the confirmed objective response rate was 39.3%; median duration of response was 15.2 months. Median progression-free survival was 8.1 months and overall survival was 23.9 months. Efficacy was relatively similar across central HER2+ testing methods. No clear association of treatment response with co-occurring biomarker alterations was seen. Few patients discontinued treatment due to adverse events; no treatment-emergent deaths occurred. Tucatinib plus trastuzumab showed clinically meaningful efficacy and favorable safety. Efficacy was observed irrespective of central HER2+ testing methods and in patients with heterogeneous tumor biomarker profiles. The MOUNTAINEER phase 2 trial demonstrated the efficacy and safety of tucatinib (HER2-targeted TKI) and trastuzumab (anti-HER2 antibody) in patients with HER2 + , RAS wildtype unresectable or metastatic colorectal cancer that had progressed on chemotherapy, resulting in the approval of the regimen. Here, the authors report the updated analysis of the MOUNTAINEER trial.
Source: Nature Communications
Authors: John H. Strickler, Andrea Cercek, Salvatore Siena, Thierry André, Kimmie Ng, Eric Van Cutsem, Christina Wu, Andrew Scott Paulson, Joleen M. Hubbard, Andrew L. Coveler, Christos Fountzilas, Adel Kardosh, Pashtoon Murtaza Kasi, Heinz-Josef Lenz, Kristen Ciombor, Elena Elez, David L. Bajor, Chiara Cremolini, Federico Sanchez, Mina Nayeri, Wentao Feng, Mark Bieda, Tanios S. Bekaii-Saab
Institutions: Duke Medical Center, Memorial Sloan Kettering Cancer Center, University of Milan, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Hôpital Saint-Antoine, Dana-Farber Cancer Institute, Universitair Ziekenhuis Leuven, KU Leuven, Mayo Clinic Hospital, The US Oncology Network, Mayo Clinic, University of Washington, Fred Hutch Cancer Center, Roswell Park Comprehensive Cancer Center, Oregon Health & Science University, OHSU Knight Cancer Institute, City of Hope, Weill Cornell Medicine, USC Norris Comprehensive Cancer Center, Vanderbilt University Medical Center, Vall d'Hebron Hospital Universitari, University Hospitals Cleveland Medical Center, Case Western Reserve University, University of Pisa, Azienda Ospedaliera Universitaria Pisana, Aurora Health Care, Pfizer (United States), Mayo Clinic in Arizona
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Pancreatic Cancer Action Network, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, Celgene, FibroGen, Array BioPharma, Regeneron Pharmaceuticals, Taiho Pharmaceutical, Exelixis, Jazz Pharmaceuticals, Les Laboratories Pierre Fabre, Agios Pharmaceuticals, BeiGene, Incyte, NuCana, Seagen, Natera, Daiichi-Sankyo, Eisai, Astellas Pharma, Servier, Swedish Orphan Biovitrum, Ipsen, Nordic Pharma Group, Aptitude Health, Genentech, Foundation Medicine, National Cancer Institute, Cilag
Award: Cancer Center Support Grant
OpenAlex ID: W7122905459