On September 4, 2020, the FDA approved Gavreto (pralsetinib) for the treatment of adults with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) detected by an FDA-approved test. This indication was approved under the FDA’s Accelerated Approval program based on data from the phase I/II ARROW study.

Continued approval for this indication may be dependent upon validation and description of clinical benefit in a confirmatory trial. Gavreto is formulated as a once-daily oral tyrosine kinase inhibitor designed to selectively and potently inhibit RET alterations that drive many cancer types, including nearly 1% to 2 % of patients with NSCLC.

Currently, RET is one of seven NSCLC biomarkers that can be targeted with an FDA-approved therapy. Preclinical data have revealed that Gavreto impedes principal RET fusions and mutations that cause cancer in subsets of patients, as well as secondary RET mutations predicted to drive resistance to treatment. In the phase I/II ARROW study, Gavreto produced robust clinical responses in individuals with RET fusion-positive NSCLC with or without prior therapy and regardless of RET fusion partner or central nervous system involvement.

Gavreto demonstrated an overall response rate (ORR) of 57% (95% CI, 46%, 68%) and complete response (CR) rate of 5.7% in the 87 individuals with NSCLC previously treated with platinum-based chemotherapy, and the average duration of response was not achieved (95% CI, 15.2 months, not achieved).

In the 27 individuals with treatment-naïve NSCLC, the ORR was 70% (95% CI, 50%, 86%), with an 11% CR rate. The most common adverse reactions reported (≥25%) were fatigue, constipation, musculoskeletal pain, and elevations in blood pressure. In a press release, Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, stated, “The FDA approval of Gavreto for RET fusion-positive non-small cell lung cancer is an important step towards our goal of providing an effective treatment option for every person diagnosed with lung cancer, no matter how rare or hard-to-treat their type of disease. We remain committed to finding personalized treatment options for people with cancer based on specific genomic or molecular alterations, and we look forward to partnering with Blueprint Medicines to further explore the potential of Gavreto across multiple RET-altered tumour types.”

Additionally, the FDA has also granted Priority Review to Gavreto for the treatment of individuals with advanced or metastatic RET-mutant Medullary Thyroid Cancer and RET fusion-positive thyroid cancer and is projected to make a decision on approval by February 28, 2021.
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