Tucatinib plus trastuzumab for chemotherapy-refractory, HER2+, RAS wild-type metastatic colorectal cancer (MOUNTAINEER): Final analysis
Authors
John H. Strickler, Duke University Medical Center, Durham, NC, USA.
Andrea Cercek, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Salvatore Siena, Università degli Studi di Milano, Milan, Italy.
Thierry André, Department of Medical Oncology, Sorbonne University, Saint-Antoine Hospital, AP-HP, Paris, France.
Kimmie Ng, Dana-Farber Cancer Institute, Boston, MA, USA.
Eric Van Cutsem, University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium.
Christina Wu, Mayo Clinic, Phoenix, AZ, USA.
Andrew Scott Paulson, Texas Oncology/The US Oncology Network, Dallas, TX, USA.
Joleen M. Hubbard, Mayo Clinic, Rochester, MN, USA.
Andrew L. Coveler, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA.
Christos Fountzilas, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Adel Kardosh, OHSU Knight Cancer Institute, Portland, OR, USA.
Pashtoon Murtaza Kasi, Weill Cornell Medicine, New York City, NY, USA.
Heinz-Josef Lenz, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Kristen Ciombor, Vanderbilt University Medical Center, Nashville, TN, USA.
Elena Elez, Vall d'Hebron University Hospital, Barcelona, Spain.
David L. Bajor, Case Western Reserve University-University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Chiara Cremolini, Azienda Ospedaliero-Universitaria Pisana and Università di Pisa, Pisa, Italy.
Federico Sanchez, Advocate Health - MidwestFollow
Mina Nayeri, Pfizer Inc, Bothell, WA, USA.
Wentao Feng, Pfizer Inc, Bothell, WA, USA.
Mark Bieda, Pfizer Inc, Bothell, WA, USA.
Tanios S. Bekaii-Saab, Mayo Clinic Arizona, Phoenix, AZ, USA. Bekaii-Saab.Tanios@mayo.edu.
Recommended Citation
Strickler JH, Cercek A, Siena S, et al. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2 + , RAS wild-type metastatic colorectal cancer (MOUNTAINEER): final analysis. Nat Commun. Published online January 12, 2026. doi:10.1038/s41467-025-67824-z
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.
