FDA Grants Priority Review to Pralsetinib for RET+ Thyroid Cancers

September 5, 2020

The FDA has granted a priority review to pralsetinib for the treatment of patients with advanced or metastatic RET-mutant medullary thyroid cancer as well as for patients with RET fusion–positive thyroid cancer.

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