On August 9, the U.S. Food and Drug Administration (FDA) granted regular approval to pralsetinib (Gavreto) for adults with metastatic RET fusion–positive non–small cell lung cancer (NSCLC), as detected by an FDA-approved test.
ARROW Trial
Pralsetinib was previously granted accelerated approval for the NSCLC indication on Septemeber 4, 2020, based on initial overall response rate and duration of response in 114 patients enrolled in the ARROW trial (ClinicalTrials.gov identifier NCT03037385), a multicenter, open-label, multicohort trial. The conversion to regular approval was based on data from an additional 123 patients and 25 months of additional follow-up to assess the durability of response.
Efficacy was demonstrated in a total of 237 patients with locally advanced or metastatic RET fusion–positive NSCLC. Patients received pralsetinib until disease progression or unacceptable toxicity.
The primary efficacy measures were overall response rate and duration of response, as determined by blinded independent review committee. Among 107 treatment-naive patients, overall response rate was 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, overall response rate was 63% (95% CI = 54%–71%), with a median duration of response of 38.8 months (95% CI = 14.8 months to not estimable).
The most common adverse reactions (≥ 25%) were musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough.
The recommended pralsetinib dose is 400 mg orally once daily. Pralsetinib is taken on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after taking pralsetinib).
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted Breakthrough Therapy designation and Orphan Drug designation.
