Genentech Gains Regular FDA Approval for Pralsetinib in RET Fusion-Positive NSCLC

Genentech's pralsetinib (Gavreto) has completed the accelerated-to-regular approval conversion that FDA's confirmatory trial framework demands, a pathway outcome regulatory teams managing oncology pipelines under breakthrough or accelerated designations should map against their own data packages. The agency granted regular approval on August 9, 2023, for adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved companion diagnostic.

The original accelerated approval, granted September 4, 2020, rested on overall response rate (ORR) and duration of response (DOR) data from 114 patients in the ARROW trial (NCT03037385), a multicenter, open-label, multi-cohort study. Conversion to regular approval required an additional 123 patients and 25 months of extended follow-up, a quantum of confirmatory evidence that sets a visible benchmark for sponsors holding accelerated designations in solid tumor indications.

Efficacy was assessed across 237 patients with locally advanced or metastatic RET fusion-positive NSCLC, with ORR and DOR determined by a Blinded Independent Review Committee (BIRC). Among 107 treatment-naïve patients, ORR reached 78% (95% CI: 68, 85) with a median DOR of 13.4 months (95% CI: 9.4, 23.1). The previously treated cohort, 130 patients with prior platinum-based chemotherapy, returned an ORR of 63% (95% CI: 54, 71) and a notably extended median DOR of 38.8 months (95% CI: 14.8, not estimable), a durability signal that anchored the conversion argument.

The safety profile across the full population identified musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough as the most common adverse reactions, each occurring in at least 25% of patients. The recommended dose remains 400 mg orally once daily, administered on an empty stomach, no food for at least two hours before or one hour after dosing, a patient-instruction detail with direct implications for medication guide and labeling review teams.

The submission carried both breakthrough therapy designation and orphan drug designation, and the review incorporated FDA's Assessment Aid, a voluntary applicant submission designed to streamline agency evaluation. For regulatory affairs leads, the ARROW trial's confirmatory data structure, extended follow-up duration, BIRC-adjudicated endpoints, and cohort stratification by prior treatment, represents a replicable template for accelerated approval conversions in molecularly defined oncology populations.

The durability data from the platinum-pretreated cohort, with a median DOR of 38.8 months, will likely anchor label negotiations and payer discussions as the product transitions into standard-of-care positioning.

Source: U.S. Food and Drug Administration, Drug Approvals and Databases, October 20, 2026.