Genentech Withdraws US Indication for Pralsetinib in Advanced or Metastatic RET+ Medullary Thyroid Cancer

The US indication for pralsetinib (Gavreto) in the treatment of adult and pediatric patients aged 12 years and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy has been voluntarily withdrawn by Genentech, according to a Securities and Exchange Commission filing from Blueprint Medicines.¹

The decision was made following consultation with the FDA and the determination that the confirmatory phase 3 AcceleRET-MTC trial (NCT04760288) required to convert the agent’s accelerated approval to full approval will no longer be pursued due to feasibility. 

New safety or efficacy data did not factor into the decision to withdraw the indication for pralsetinib in RET-mutant MTC, and other approved indications for the agent will remain unaffected. Additionally, confirmatory studies to convert accelerated approvals for pralsetinib into full approvals in other indications remain ongoing.

“[Blueprint Medicines], in partnership with Genentech, remains committed to supporting appropriate treatment continuity for [patients with] MTC in the United States who are currently treated with [pralsetinib], and to supporting patients and healthcare practitioners [to] navigate the near-term impacts of this update,” Blueprint Medicines wrote in the filing.

In December 2020, the FDA granted accelerated approval to pralsetinib for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy.²

The decision was based on findings from the phase 1/2 ARROW trial (NCT03037385), which evaluated the safety and efficacy of pralsetinib in patients with RET fusion–positive non–small cell lung cancer, RET-mutated MTC, RET fusion–positive thyroid cancer, and other RET-altered solid tumors.

Among 55 patients with RET-mutant MTC who received prior treatment with either cabozantinib (Cabometyx) or vandetanib (Caprelsa), pralsetinib elicited an overall response rate (ORR) of 60% (95% CI, 46%-73%), and 79% of responders experienced responses that lasted at least 6 months. Additionally, in 29 patients who did not receive prior treatment with cabozantinib or vandetanib, the ORR was 66% (95% CI, 46%-82%), with 84% of responses lasting at least 6 months.

Regarding safety, the most common any-grade adverse effects that were reported in at least 25% of patients included constipation, hypertension, fatigue, musculoskeletal pain, and diarrhea. Grade 3 or 4 laboratory abnormalities that were reported in at least 2% of patients consisted of decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased calcium, decreased sodium, increased aspartate aminotransferase, increased alanine aminotransferase, decreased platelets, and increased alkaline phosphatase.

AcceleRET-MTC was slated to compare pralsetinib with investigator’s choice of standard-of-care cabozantinib or vandetanib in patients with RET-mutant MTC who had not received prior treatment with a multikinase inhibitor.³

References

1. United States Securities and Exchange Commission: Form 8-K. Blueprint Medicines. June 30, 2023. Accessed June 30, 2023. https://ir.blueprintmedicines.com/static-files/bffb2116-8151-4a0f-84bb-6f0bd5fdbb23
2. FDA approves pralsetinib for RET-altered thyroid cancers. News release. FDA. December 1, 2020. Accessed June 30, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pralsetinib-ret-altered-thyroid-cancers
3. A study of pralsetinib versus standard of care (SOC) for treatment of RET-mutated medullary thyroid cancer (MTC). (AcceleRET-MTC). ClinicalTrials.gov. Updated June 18, 2023. Accessed June 30, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04760288