FDA grants accelerated approval to tucatinib with trastuzumab for colorectal cancer

FDA accelerated approval: tucatinib + trastuzumab in HER2+ colorectal cancer

Type: Regulatory approval (accelerated approval)
Date: 2023-01-19

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

Supporting evidence

Efficacy was evaluated in MOUNTAINEER (NCT03043313), an open-label, multicenter trial enrolling 84 patients with HER2-positive, RAS wild-type unresectable/metastatic colorectal cancer. Prior therapy requirements included fluoropyrimidine, oxaliplatin, irinotecan, and an anti-VEGF mAb; patients with dMMR/MSI-H tumors must also have received an anti–PD-1 mAb. Prior anti-HER2 therapy was excluded.

Patients received tucatinib 300 mg orally twice daily plus trastuzumab (8 mg/kg IV loading dose, then 6 mg/kg IV every 21 days) until progression or unacceptable toxicity. Major endpoints were ORR and DOR by blinded independent central review (RECIST 1.1): ORR 38% (95% CI 28–49) and median DOR 12.4 months (95% CI 8.5–20.5).

Safety (common events ≥20%)

AEs: diarrhea, fatigue, rash, nausea, abdominal pain, infusion-related reactions, pyrexia. Common lab abnormalities included increased creatinine, glucose, ALT/AST, bilirubin, alkaline phosphatase; decreased hemoglobin, lymphocytes, albumin, leukocytes, sodium.

The review occurred under Project Orbis; FDA collaborated with Australia’s TGA, with review ongoing at the other agency.