Tucatinib plus trastuzumab for chemotherapy-refractory, HER2 + , RAS wild-type metastatic colorectal cancer (MOUNTAINEER): final analysis
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.
Authors
- John Strickler
- Wentao Feng (ORCID: https://orcid.org/0000-0003-3979-9983)
- A. Cercek
- Andrew Scott Paulson (ORCID: https://orcid.org/0009-0000-6023-670X)
- Joleen M. Hubbard (ORCID: https://orcid.org/0000-0001-8250-4920)
- Mina Nayeri
- Mark Bieda (ORCID: https://orcid.org/0000-0002-0429-1373)
- C. Fountzilas
- Salvatore Siena
- Andrew L. Coveler (ORCID: https://orcid.org/0000-0003-1710-5637)
- K. Ng
- Pashtoon Murtaza Kasi (ORCID: https://orcid.org/0000-0002-5169-7085)
- David L. Bajor (ORCID: https://orcid.org/0000-0003-2702-5008)
- Elena M Elez
- Chiara Cremolini
- C. Wu
- Eric Van Cutsem
- Tanios S. Bekaii-Saab
- Kristen Keon Ciombor
- Federico Sanchez
- Thierry Andre
- Adel Kardosh
- Heinz-Josef Lenz
Institutions
- Roswell Park Comprehensive Cancer Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- Pfizer (United States) (US)
- University of Milan (IT)
- University of Washington (US)
- Cornell University (US)
- University Hospitals of Cleveland (US)
- Texas Oncology (US)
- Universitair Ziekenhuis Leuven (BE)
- Sorbonne Université (FR)
- Fred Hutch Cancer Center (US)
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
- Assistance Publique – Hôpitaux de Paris (FR)
- Hôpital Saint-Antoine (FR)
- HOPE Clinic (US)
- USC Norris Comprehensive Cancer Center (US)
- Dana-Farber Cancer Institute (US)
- Mayo Clinic in Arizona (US)
- Duke Medical Center (US)
- Vall d'Hebron Hospital Universitari (ES)
- Mayo Clinic Hospital (US)
- The US Oncology Network (US)
- Azienda Ospedaliera Universitaria Pisana (IT)
- Weill Cornell Medicine (US)
- OHSU Knight Cancer Institute
- Vanderbilt University Medical Center (US)
- KU Leuven (BE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-01-12
- DOI
- https://doi.org/10.1038/s41467-025-67824-z
- Citations
- 2
- Primary Topic
- HER2/EGFR in Cancer Research
- Type
- article
- Field-Weighted Citation Impact
- 48.39
Funders
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Sanofi
- Regeneron Pharmaceuticals
- Jazz Pharmaceuticals
- BeiGene
- Seagen
- Natera
- Daiichi-Sankyo
- Astellas Pharma
- Genentech