On December 1, 2020, the U.S. Food and Drug Administration (FDA) approved pralsetinib (Gavreto™) for patients aged 12 years and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy or RET fusion-positive therapy and who are refractory to radioactive iodine (if radioactive iodine is appropriate).
Efficacy was investigated in a multicenter, open-label, multicohort clinical trial (ARROW; NCT03037385) in patients whose tumors had RET gene alterations. Identification of RET gene alterations was prospectively determined in local laboratories using either next-generation sequencing, fluorescence in situ hybridization, or other tests.
The main efficacy outcome measures were overall response rate (ORR) and response duration determined by a blinded independent review committee using response evaluation criteria in solid tumors 1.1. Efficacy for advanced or metastatic RET-mutant MTC was evaluated in 55 patients who had received prior cabozantinib or vandetanib. ORR for those patients was 60% (95% CI = 46%, 73%); 79% had responses lasting six months or longer. Efficacy was also evaluated in 29 patients with RET-mutant MTC who did not receive prior cabozantinib or vandetanib. ORR was 66% (95% CI = 46%, 82%); 84% of patients had responses lasting six months or longer. Efficacy for patients with RET fusion-positive thyroid cancer was evaluated in nine patients who were refractory to radioactive iodine. ORR was 89% (95% CI = 52%, 100%); all responding patients had responses lasting six months or longer.
The most common adverse reactions (≥ 25%) were constipation, hypertension, fatigue, musculoskeletal pain, and diarrhea. The most common grade 3–4 laboratory abnormalities (≥ 2%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased calcium (corrected), decreased sodium, increased aspartate aminotransferase, increased alanine aminotransferase, decreased platelets, and increased alkaline phosphatase.
The recommended pralsetinib dose is 400 mg orally once daily on an empty stomach with no food intake for at least two hours before and at least one hour after.
View full prescribing information for pralsetinib.
The review used the Real-Time Oncology Review pilot program and Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved this application three months ahead of its goal date.
FDA granted the application accelerated approval based on ORR and duration of response. Continued approval for the indication is contingent upon verification and description of clinical benefit in confirmatory trials.
FDA granted the application priority review, breakthrough therapy, and orphan drug designations. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics.
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 or by calling 800-FDA-1088.
For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.