RET Inhibitor Gavreto (Pralsetinib) Receives Full FDA Approval for RET Fusion-Positive NSCLC with 78% Overall Response Rate in Treatment-Naïve Patients

▎WuXi

Edited by Kant Content Team

Recently, the U.S. FDA announced the full approval of the drug Gavreto (pralsetinib), developed by Blueprint Medicines and Genentech, for the treatment of adult patients with RET fusion-positive non-small cell lung cancer (NSCLC) as determined by an FDA-approved test.

RET activating gene fusions and mutations are key drivers in many cancer types, including NSCLC and various forms of thyroid cancer. Approximately 1-2% of NSCLC patients and 10-20% of thyroid cancer patients harbor RET fusions, while around 90% of advanced medullary thyroid carcinoma (MTC) patients carry RET mutations.

Gavreto is a once-daily oral RET-targeted therapy.It can specifically and potently inhibit RET alterations that drive many types of cancer. This therapy received orphan drug designation and breakthrough therapy designation from the U.S. FDA, and was granted accelerated approval by the FDA in September 2020 for the treatment of adult patients with RET fusion-positive non-small cell lung cancer.

This approval is based on efficacy data from a total of 237 patients with locally advanced or metastatic RET fusion-positive NSCLC. Patients received Gavreto treatment until disease progression or the appearance of unacceptable toxicity.

The primary efficacy endpoints were the overall response rate (ORR) and duration of response (DOR) as determined by the blinded independent review committee (BIRC).In 107 treatment-naïve patients, the ORR was 78% (95% CI: 68-85), with a median DOR of 13.4 months (95% CI: 9.4-23.1). In 130 patients previously treated with 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 adverse reactions (≥25%) were musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, fever, and cough.