FDA Grants Accelerated Approval to Tucatinib With Trastuzamab for RAS Wild-Type HER2-Positive Colorectal Cancer

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

The approval was based on results from the ongoing open-label, multicenter phase 2 MOUNTAINEER trial, which enrolled 84 patients with RAS wild-type HER2-positive unresectable or metastatic colorectal cancer who had previously been treatment with fluoropyrimidine, oxaliplatin, irinotecan, and an anti-vascular endothelial growth factor (VEGF) monoclonal antibody. Patients received 300 mg oral tucatinib twice a day, administered with a loading dose of 8 mg/kg of intravenous trastuzumab on day 1 of cycle 1, followed by a maintenance dose of 6 mg/kg intravenous trastuzumab on day 1 of every 21-day cycle, with treatment continuing until disease progression or unacceptable toxicity.

The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), assessed by blinded independent central review. Among the 84 patients studied, ORR was 38% (95% confidence interval [CI], 28 to 49) with a median DOR of 12.4 months (95% CI, 8.5 to 20.5).

The most common treatment-related adverse events, reported in ≥20% of patients, were diarrhea, fatigue, rash, nausea, abdominal pain, infusion related reactions, and pyrexia. The most common laboratory abnormalities, reported in ≥20% of patients, were increased creatinine, increased glucose, increased ALT, decreased hemoglobin, increased AST, increased bilirubin, increased alkaline phosphatase, decreased lymphocytes, decreased albumin, decreased leukocytes, and decreased sodium.

Source:

FDA grants accelerated approval to tucatinib with trastuzumab for colorectal cancer. Press Release. United States Food and Drug Administration. January 19, 2023. Accessed January 19, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tucatinib-trastuzumab-colorectal-cancer