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Gavreto Received Regular FDA Approval for Patients With Non–Small Cell Lung Cancer and RET Gene Fusion

Web Exclusives - FDA Approvals

On August 9, 2023, the FDA granted regular approval to pralsetinib (Gavreto; Genentech) for the treatment of adults with metastatic non–small cell lung cancer (NSCLC) and RET fusion–positive gene mutation, as detected by an FDA-approved test. This application was granted breakthrough and orphan drug designations.

Pralsetinib is a kinase inhibitor of wild-type RET and oncogenic RET fusions and mutations and is available as oral capsules.

Oral pralsetinib is also indicated for the treatment of patients aged ≥12 years with advanced or metastatic RET fusion–positive thyroid cancer who require systemic therapy and whose tumor is refractory to radioactive iodine (if treatment with radioactive iodine is appropriate).

On September 4, 2020, the FDA accelerated the approval of pralsetinib capsules for the treatment of metastatic NSCLC with RET-activating fusions based on the initial overall response rate (ORR) and duration of response (DOR) of 114 patients with NSCLC and RET-positive fusion who were enrolled in the ARROW study (NCT03037385), a multicenter, open-label, multicohort clinical trial. At that same time, the FDA also approved Oncomine Dx as a companion diagnostic test with pralsetinib.

In response to this accelerated approval, Vivek Subbiah, MD, Associate Professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center and investigator on the ARROW study, said, “Patients treated with Gavreto had durable clinical responses, with a subset achieving complete responses characterized by the resolution of all target lesions, an uncommon outcome in metastatic lung cancer.”

The FDA’s conversion of the accelerated approval for NSCLC and RET-positive fusion to regular approval was based on the results of an additional 123 patients, for a total of 237 patients, during a further 25 months of follow-up that was conducted to evaluate the durability of the response to pralsetinib capsules in patients with locally advanced or metastatic NSCLC and RET fusion. The patients received pralsetinib therapy until disease progression or unacceptable adverse events.

The primary efficacy measures in the ARROW study were ORR and DOR, as determined by a blinded independent review committee. Among 107 treatment-naïve patients, the ORR was 78% (95% confidence interval [CI], 68-85), with a median DOR of 13.4 months (95% CI, 9.4-23.1). Among 130 patients who had received platinum-based chemotherapy, the ORR was 63% (95% CI, 54-71), with a median DOR of 38.8 months (95% CI, 14.8-not estimable).

The most common (≥25%) adverse events in the ARROW trial were musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough.

The recommended dose of pralsetinib capsules is 400 mg orally once daily. Pralsetinib should be taken on an empty stomach (with no food intake for at least 2 hours before and at least 1 hour after taking this medication).

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Last modified: September 8, 2023