On August 9, 2023, the U.S. Food and Drug Administration (FDA) granted regular approval to pralsetinib (Gavreto®) for adult patients with metastatic, rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.

FDA Approves Pralsetinib for Non-Small Cell Lung Cancer With RET Gene Fusions

Pralsetinib was previously granted accelerated approval for the indication in September 2020 based on the initial overall response rate (ORR) and duration of response (DOR) in 114 patients enrolled in the ARROW trial (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 durability of response.

The efficacy was demonstrated in a total of 237 patients with locally advanced or metastatic RET fusion-positive NSCLC. Patients received pralsetinib until they experienced disease progression or unacceptable toxicity.

The primary efficacy measures were ORR and DOR, as determined by a blinded independent review committee. Among 107 treatment-naive patients, ORR was 78% (95% CI = 68, 85) with a median DOR of 13.4 months (95% CI = 9.4, 23.1). Among 130 patients previously treated with platinum-based chemotherapy, ORR was 63% (95% CI = 54, 71) with a median DOR of 38.8 months (95% CI = 14.8, not estimable).

The most common adverse reactions reported in at least 25% of patients treated with pralsetinib 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 at least two hours after or one hour before eating.

View the full prescribing information for pralsetinib.

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

The application was granted breakthrough designation and orphan drug designation. FDA expedited programs are described in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088. 

For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov