Tucatinib Plus Trastuzumab Yields Positive Topline Data in Phase 2 MOUNTAINEER Trial for HER2+ mCRC


In the phase 2 MOUNTAINEER trial, patients with previously treated HER2-positive metastatic colorectal cancer who were treated with tucatinib plus trastuzumab were shown to have an improved objective response rate.

Treatment with tucatinib (Tukysa) and trastuzumab (Herceptin) in patients with previously treated HER2-positive metastatic colorectal cancer yielded promising responses, according to topline findings from the phase 2 MOUNTAINEER trial (NCT03043313).1

The primary end point of confirmed objective response rate (ORR) by blinded independent central review (BICR) was 38.1% (95% CI, 27.7%-49.3%) in patients who received treatment with the combination. Moreover, the median duration of response by BICR was 12.4 months (95% CI, 8.5-20.5). Patients tolerated the combination well, and the most common adverse effects in 20% or more of patients were diarrhea, fatigue, nausea, and infusion-related reaction, all of which were notably low grade.

“People with HER2-positive previously treated metastatic [CRC] have a significant unmet need for new therapies. We are excited by the potential for this tucatinib combination to help patients based on the excellent anti-tumor activity with durable responses and a tolerable safety profile,” Roger Dansey, MD, interim chief marketing officer and chief medical officer at Seagen, said in the press release. “Based on the strength of these data, we are planning to engage in regulatory discussions with the FDA with the intent to submit a supplemental New Drug Application for tucatinib.”

During a trials in progress presentation at the 2021 American Society of Clinical Oncology Gastrointestinal (GI) Cancer Symposium, investigators reported that a total of 117 patients enrolled on the trial.2 There were 3 cohorts in the study. Patients in cohort A (n = 45) received tucatinib at 300 mg twice orally per day and trastuzumab at 8 mg/kg intravenously followed by 6 mg/kg every 3 weeks. The trial was expanded to enroll 70 patients, 40 of whom were in cohort B and received the combination regimen and 30 patients in cohort C received tucatinib monotherapy; those who did not respond to therapy had the option to receive the combination therapy.

Secondary end points included duration of response, progression-free survival, overall survival, and safety in cohorts A and B.

Patients were eligible for treatment if they had histologically or cytologically confirmed adenocarcinoma of the colon or rectum that was metastatic or unresectable. Patients also previously received and progressed on treatment with fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF monoclonal antibody, and an anti-PD-L1 therapy. Additionally, patients must have progressive disease after last systemic therapy or be intolerable to it, have RAS wild-type disease in primary or metastatic tumor tissue, and have confirmed HER2-positive disease.

Exclusion criteria included having previous treatment with an anti-HER2 targeting therapy, previous treatment with systemic anticancer therapy, and toxicity related to prior cancer therapies that have not been resolved. Those with a clinically significant cardiopulmonary disease, major surgical procedures within 28 days of enrollment, and a serious non-healing wound, ulcer, or bone fracture were not able to enroll on the study.

The full results of the trial will be presented at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer from June 29 to July 2, 2022.


  1. Seagen announces positive topline results of pivotal phase 2 clinical trial of Tukysa (tucatinib) in combination with trastuzumab in HER2-positive metastatic colorectal cancer. News Release. May 23, 2022. Accessed May 23, 2022. https://bit.ly/3NyFW3N
  2. MOUNTAINEER: open-label, phase II study of tucatinib combined with trastuzumab for HER2-positive metastatic colorectal cancer (SGNTUC-017, trial in progress). J Clin Oncol. 39(suppl 3). doi:10.1200/JCO.2021.39.3_suppl.TPS153
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