Tukysa Combo Approved for RAS Wild-Type, HER2-Positive Metastatic Colorectal Cancer

The approval was based on data from the phase 2 MOUNTAINEER trial, which included patients with HER2-positive unresectable or metastatic colorectal cancer.

The 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 multicenter, open-label phase 2 MOUNTAINEER trial (ClinialTrials.gov 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 targeting therapy were excluded from the study.

Study participants 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). 

Findings demonstrated an ORR of 38% (95% CI, 28-49); among responders, 3.6% achieved complete response and 35% achieved partial response. Median duration of response (DOR) was 12.4 months (95% CI, 8.5-20.5), with 81% of patients maintaining response for at least 6 months and 34% maintaining response for at least 12 months.

The most common adverse reactions 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, Duke University Medical Center, and lead investigator for 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 tumor response rate and durability of response. The ongoing phase 3 MOUNTAINEER-03 trial (ClinicalTrials.gov Identifier: NCT05253651) is intended to serve as a confirmatory trial and will compare Tukysa in combination with trastuzumab and mFOLFOX6 with standard of 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. https://investor.seagen.com/press-releases/news-details/2023/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/default.aspx.
  2. Tukysa. Package insert. Seagen; 2022. Accessed January 19, 2023. https://docs.seagen.com/TUKYSA_Full_Ltr_Master.pdf.