FDA Approves Pralsetinib (Gavreto) for Regular Use in the Treatment of RET Gene Fusion-Positive Non-

On August 9, 2023, the U.S. Food and Drug Administration (FDA) approved pralsetinib (trade name: Gavreto, developed by Genentech) for regular use in adult patients with metastatic rearranged during transfection (RET) gene fusion-positive non-small cell lung cancer (NSCLC) confirmed by an FDA-approved testing method.

Previously, on September 4, 2020, pralsetinib had received accelerated approval for the aforementioned NSCLC indication based on preliminary data of objective response rate (ORR) and duration of response (DOR) from 114 subjects in the multicenter, open-label, multi-cohort ARROW clinical trial (trial number: NCT03037385). The conversion of this approval to regular approval was based on research data from an additional 123 subjects and follow-up results extending for an extra 25 months, which were used to evaluate the durability of efficacy.

The efficacy of this drug has been verified in a total of 237 patients with locally advanced or metastatic RET gene fusion-positive NSCLC. Subjects received continuous pralsetinib treatment until disease progression or intolerable toxic reactions occurred.

The primary efficacy endpoints of this study were the objective response rate (ORR) and duration of response (DOR) assessed by the Blinded Independent Review Committee (BIRC).

Among 107 treatment-naive patients, the objective response rate reached 78% (95% confidence interval [CI]: 68%–85%), with a median duration of response of 13.4 months (95% CI: 9.4–23.1 months).

Among 130 patients previously treated with platinum-based chemotherapy, the objective response rate was 63% (95% CI: 54%–71%), with a median duration of response of 38.8 months (95% CI: 14.8 months–not reached).

The most common adverse reactions to pralsetinib (incidence rate ≥ 25%) include musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, fever and cough.

The recommended dosage of pralsetinib is 400 mg orally once daily, and it should be taken on an empty stomach (fasting for at least 2 hours before administration and at least 1 hour after administration).