FDA Grants Priority Review to Tucatinib Plus Trastuzumab for Previously Treated HER2+ Metastatic CRC

Patients with previously treated, metastatic, HER2-positive colorectal cancer may benefit from treatment with tucatinib and trastuzumab, which was granted priority review by the FDA.

Tucatinib (Tukysa) and trastuzumab (Herceptin) was granted priority review by the FDA as a treatment for patients with HER2-positive metastatic colorectal cancer (CRC) who have undergone treatment with at least 1 regimen for unresectable or metastatic disease, according to a press release from Seagen.1

The combination’s supplemental new drug application is supported by findings from the phase 2 MOUNTAINEER trial (NCT03043313). Findings from the study, which were presented at the 2022 European Society of Medical Oncology Congress on Gastrointestinal Cancer, indicated that after a median follow-up of 20.7 months, HER2-positive patients treated with the combination (n = 84) experienced a confirmed objective response rate (ORR) of 38.1% (95% CI, 27.7%-49.3%) by blinded independent central review.2 The median duration of response (DOR) was 12.4 months (95% CI, 8.5-20.5) and the median progression-free survival (PFS) was 8.2 months (95% CI, 4.2-10.3). Additionally, the median overall survival (OS) was 24.1 months (95% CI, 20.3-36.7).

The FDA has settled on a prescription drug user fee act date of January 19, 2023.

“There are currently no FDA-approved therapies for metastatic colorectal cancer that specifically target HER2,” Marjorie Green, MD, senior vice president and Head of Late-Stage Development at Seagen, said in the press release. “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.”

Patients received 300 mg of oral tucatinib twice daily plus an 8 mg/kg loading dose of intravenous trastuzumab followed by 6 mg/kg subsequently every 3 weeks. The study’s primary end point was confirmed ORR, with key secondary end points including DOR, PFS, OS, and safety and tolerability.

The most common treatment-emergent adverse effects (TEAEs) of any grade included diarrhea, fatigue, nausea, and infusion reactions. Additionally, the most frequent grade 3 of higher AE was hypertension (7.0%). Serious AEs occurred in 26% of patients treated with tucatinib, and included diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), seizure (2%).Two percent of patients experienced an AE that led to death.

The combination regimen will be further evaluated with the addition of chemotherapy in the first line vs chemotherapy plus or minus cetuximab (Erbitux) or bevacizumab (Avastin) in patients with HER2-positive metastatic CRC as part of the global phase 3 MOUNTAINEER-03 trial (NCT05253651).


  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. September 19, 2022. Accessed September 20, 2022. https://bit.ly/3eXiyB3
  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 20, 2022. https://bit.ly/3BR2Dxk