The US Food and Drug Administration (FDA) has granted accelerated approval to Tukysa (tucatinib) in combination with trastuzumab for the treatment of adults with RAS wild-type, HER2-positive, unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

The approval was based on data from the phase 2 MOUNTAINEER trial ( Identifier: NCT03043313), which included 84 patients with HER2-positive, RAS wild-type, unresectable or metastatic colorectal cancer following previous standard of care therapies. Patients who received prior anti-HER2 therapy were excluded from the study.

Study participants received tucatinib at 300 mg orally twice daily in combination with trastuzumab intravenously (8 mg/kg loading dose, then 6 mg/kg every 3 weeks thereafter).

Continue Reading

The objective response rate was 38%, and the complete response rate was 3.6%. The median duration of response was 12.4 months, with 81% of patients maintaining a response for at least 6 months and 34% maintaining a response for at least 12 months.

The most common adverse events reported were diarrhea, fatigue, rash, nausea, abdominal pain, infusion-related reactions, and pyrexia. 

“Historically, patients with HER2-positive metastatic colorectal cancer who have progressed following frontline therapy have had poor outcomes,” said John Strickler, MD, associate professor of medicine at Duke University Medical Center and lead investigator of the MOUNTAINEER trial. “The FDA approval of a chemotherapy-free combination regimen that specifically targets HER2 is great news for these patients.”

The accelerated approval of the combination therapy was based on response rate and durability of response. The ongoing phase 3 MOUNTAINEER-03 trial ( Identifier: NCT05253651) is intended to serve as a confirmatory trial and will compare tucatinib plus trastuzumab and mFOLFOX6 with standard care.


  1. Seagen announces FDA accelerated approval of Tukysa® (tucatinib) in combination with trastuzumab for people with previously treated RAS wild-type, HER2-positive metastatic colorectal cancer. News release. Seagen. Accessed January 19, 2023.
  2. Tukysa. Package insert. Seagen; 2022. Accessed January 19, 2023.

This article originally appeared on MPR