FDA approved

FDA Approval: Tucatinib with Trastuzumab for colorectal cancer

  • January 23, 2023
  • < 1 min read

The U.S FDA approved the combination of drugs Tucatinib and Trastuzumab on January 19, 2023, for RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. 

Efficacy was evaluated in 84 patients in MOUNTAINEER (NCT03043313), an open-label, multicenter trial. Patients were required to have HER2-positive, RAS wild-type, unresectable or metastatic colorectal cancer and prior treatment with fluoropyrimidine, oxaliplatin, irinotecan, and an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb). Patients whose tumors were deficient in mismatch repair (dMMR) proteins or were microsatellite instability-high (MSI-H) must also have received an anti-programmed cell death protein-1 mAb. Patients who received prior anti-HER2 targeting therapy were excluded.

Patients received tucatinib 300 mg orally twice daily with trastuzumab (or a non-U.S. approved trastuzumab product) administered at a loading dose of 8 mg/kg intravenously on Day 1 of Cycle 1 followed by a maintenance dose of trastuzumab 6 mg/kg on Day 1 of each subsequent 21-day cycle. Patients were treated until disease progression or unacceptable toxicity.

The most common adverse events (≥20%) were diarrhea, fatigue, rash, nausea, abdominal pain, infusion-related reactions, and pyrexia.

The recommended tucatinib dose is 300 mg taken orally twice daily in combination with trastuzumab until disease progression or unacceptable toxicity.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted priority review and breakthrough therapy designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Tukysa was granted orphan drug designation for the treatment of HER2+ colorectal cancer.

Reference: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tucatinib-trastuzumab-colorectal-cancer