On September 4, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pralsetinib (Gavreto™) for adult patients with metastatic, RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test.
FDA also approved the Oncomine Dx Target Test as a companion diagnostic for pralsetinib.
Efficacy was investigated in a multicenter, open-label, multicohort clinical trial (ARROW; NCT03037385) of patients whose tumors had RET alterations. RET gene alterations were prospectively identified in local laboratories using either next-generation sequencing, fluorescence in situ hybridization, or other tests. The main efficacy outcome measures were overall response rate (ORR) and response duration determined by a blinded independent review committee using response evaluation criteria in solid tumors 1.1.
Efficacy for RET fusion-positive NSCLC was evaluated in 87 patients previously treated with platinum chemotherapy. ORR was 57% (95% CI = 46%, 68%); 80% of responding patients had responses lasting six months or longer. Efficacy was also evaluated in 27 patients who never received systemic treatment. ORR for those patients was 70% (95% CI = 50%, 86%); 58% of responding patients had responses lasting six months or longer.
The most common adverse reactions (≥ 25%), including laboratory abnormalities, were increased aspartate aminotransferase, decreased hemoglobin, decreased lymphocytes, decreased neutrophils, increased alanine aminotransferase, increased creatinine, increased alkaline phosphatase, fatigue, constipation, musculoskeletal pain, decreased calcium, hypertension, decreased sodium, decreased phosphate, and decreased platelets.
The recommended pralsetinib dose is 400 mg orally once daily on an empty stomach (no food intake for at least two hours before and at least one hour after).
The review used Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application approximately three months prior to its goal date.
FDA granted the application accelerated approval based on ORR and response duration. Continued approval may be contingent upon verification of clinical benefit in confirmatory trials.
FDA also granted the application priority review, breakthrough therapy, and orphan drug designation. A description of FDA expedited programs is 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 oncology investigational new drug applications, contact the Oncology Center of Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.