On 4 September 2020, the US Food and Drug Administration (FDA) granted accelerated approval to pralsetinib (GAVRETOTM, Blueprint Medicines Corporation) 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 (ODxT) Test (Life Technologies Corporation) as a companion diagnostic for pralsetinib.

Efficacy was investigated in a multicentre, open-label, multi-cohort clinical trial (ARROW, NCT03037385) in patients whose tumours had RET alterations. Identification of RET gene alterations was prospectively determined in local laboratories using either next generation sequencing, fluorescence in situ hybridisation, or other tests. The main efficacy outcome measures were overall response rate (ORR) and response duration determined by a blinded independent review committee using RECIST v1.1.

Efficacy for RET fusion-positive NSCLC was evaluated in 87 patients previously treated with platinum chemotherapy. The ORR was 57% (95% confidence interval [CI] 46%, 68%); 80% of responding patients had responses lasting 6 months or longer. Efficacy was also evaluated in 27 patients who never received systemic treatment. The ORR for these patients was 70% (95% CI 50%, 86%); 58% of responding patients had responses lasting 6 months or longer.

The most common adverse reactions, including laboratory abnormalities, (≥25%) were increased aspartate aminotransferase, decreased haemoglobin, 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. Pralsetinib is taken on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after taking pralsetinib).

Full prescribing information for GAVRETO is available here.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was approved approximately 3 months prior to the FDA goal date.

This application was granted accelerated approval based on ORR and response duration. Continued approval may be contingent upon verification of clinical benefit in confirmatory trial(s).

This application was granted priority review, breakthrough therapy, and orphan drug designation.

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.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.