FDA Grants Priority Review to Pralsetinib for RET+ Thyroid Cancers

The FDA has granted a priority review to pralsetinib (formerly BLU-667; Gavreto) for the treatment of patients with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) as well as for patients with RET fusion–positive thyroid cancer, according to a press release from Genentech.¹

The New Drug Application (NDA) was accepted for review under the FDA’s Real-Time Oncology Review program, which seeks to provide a more efficient review process to provide safe and effective treatments to patients as soon as possible. A decision on the approval is expected to be made by February 28, 2021.

Pralsetinib is a once daily oral RET inhibitor that has demonstrated efficacy in treating a variety of solid tumors with RET alterations, including thyroid cancers. The agent is being co-commercialized by Blueprint Medicines and Genentech (Roche).

In thyroid cancers, RET fusions can be found in about 10% to 20% of papillary thyroid cancers, mutations are found in about 50% of sporadic MTCs, and germline mutations as a part of multiple endocrine neoplasia type 2 (MEN2) syndrome in almost 100% of MTCs.

Findings supporting the NDA came from the open-label phase 1/2 ARROW trial that is studying the safety and efficacy of pralsetinib in patients with RET fusion–positive non–small cell lung cancer, RET-mutant MTC, RET fusion–positive thyroid cancer, and other RET-altered solid tumors (NCT03037385). The trial consists of a dose-escalation phase and an expansion phase, which is administering treatment at 400 mg once daily.

In the RET-mutant MTC population, the objective response rate (ORR) was 74% among treatment-naïve patients (n = 19) and 60% (95% CI, 46%-74%) among patients previously treated with an approved multikinase inhibitor (n = 53). The median duration of response was not reached in either group. In the previously treated group, the duration of response rate at 18 months was 90% (95% CI, 77%-100%). In the treatment-naïve group, 12 of 14 responders had responses ongoing for up to 15 months.²

Among patients with RET fusion–positive thyroid cancer (n = 11), the ORR was 91% (95% CI, 59%-100%) and the remaining patient had stable disease. The disease control rate was 100% (95% CI, 72%-100%).³

The majority of treatment-related adverse events (TRAEs) were grade 1 or 2. The most frequent TRAEs were anemia (33%), increased aspartate aminotransferase (33%), decreased white blood cell counts (33%), hypertension (30%), increased alanine aminotransferase (26%), hyperphosphatemia (19%), and neutropenia (19%). In the overall patient population (n = 438), only 4% discontinued treatment due to TRAEs.²

The priority review was granted at the same time as the FDA approved pralsetinib for the treatment of adult patients with RET fusion–positive non–small cell lung cancer.

_References

_{1. Genentech Announces FDA Approval of Gavreto (pralsetinib) for the Treatment of Adults With Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer. News release. Genentech. September 4, 2020. Accessed September 4, 2020. https://bit.ly/2EYHZRe​}

_{2. Blueprint Medicines announces the achievement of key portfolio milestones. News release. Blueprint Medicines Corporation. April 1, 2020. Accessed September 4, 2020. https://bit.ly/2R3cW9R​}

_{3. Subbiah V, Hu MI, Gainor JF, et al. Clinical activity of the RET inhibitor pralsetinib (BLU-667) in patients with RET fusion+ solid tumors. J Clin Oncol. 2020;38(suppl 15):109. doi:10.1200/JCO.2020.38.15_suppl.109}