The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental New Drug Application (sNDA) for tucatinib in combination with trastuzumab for adult patients with HER2-positive colorectal cancer who have received at least 1 prior treatment regimen for unresectable or metastatic disease.

The sNDA is based on data from the multicenter, open-label phase 2 MOUNTAINEER trial ( Identifier: NCT03043313), which evaluated tucatinib in combination with trastuzumab, an HER2 inhibitor, or as a single agent in 117 patients with HER2-positive unresectable or metastatic colorectal cancer following previous standard of care therapies. Patients received tucatinib 300mg orally twice daily in combination with trastuzumab intravenously (8mg/kg loading dose, then 6mg/kg every 3 weeks thereafter).

The primary endpoint was confirmed objective response rate (ORR). Key secondary endpoints included duration of response (DoR), progression-free survival (PFS), and overall survival (OS).

At a median duration of follow-up of 20.7 months, the ORR was reported to be 38.1% (95% CI, 27.7-49.3) among the 84 patients who received tucatinib plus trastuzumab. Median DoR, PFS, and OS was 12.4 months (95% CI, 8.5-20.5), 8.2 months (95% CI, 4.2-10.3) and 24.1 months (95% CI, 20.3-36.7), respectively.

The most common treatment-emergent adverse events were diarrhea, fatigue, nausea and infusion-related reaction. The most common adverse event of grade 3 or worse was hypertension. 

“There are currently no FDA-approved therapies for metastatic colorectal cancer that specifically target HER2,” said Marjorie Green, MD, Senior Vice President and Head of Late-Stage Development, Seagen. “The FDA’s prioritization of our application for tucatinib in combination with trastuzumab supports our belief in its significant potential to benefit people with previously treated HER2-positive metastatic colorectal cancer.”

A Prescription Drug User Fee Act target action date of January 19, 2023 has been set for the application.

Tucatinib, a tyrosine kinase inhibitor of the HER2 protein, is currently marketed under the brand name Tukysa®, for use in combination with trastuzumab and capecitabine, for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received 1 or more prior anti-HER2-based regimens in the metastatic setting.


  1. Seagen announces Tukysa® (tucatinib) in combination with trastuzumab granted Priority Review by FDA for previously treated HER2-positive metastatic colorectal cancer. News release. Seagen. Accessed September 19, 2022.
  2. Seagen announces results from pivotal MOUNTAINEER trial demonstrating clinically meaningful antitumor activity of Tukysa® (tucatinib) in combination with trastuzumab in previously treated HER2-positive metastatic colorectal cancer. News release. Seagen. July 2, 2022. Accessed September 19, 2022.