Selpercatinib Wins FDA Accelerated Approval for RET-Altered Tumors in Pediatric Patients

• The FDA has granted accelerated approval to selpercatinib (Retevmo) for the treatment of patients aged 2 and older with RET-altered thyroid cancer or solid tumors.
• This marks the first FDA approval of a targeted therapy for patients under the age of 12 with RET alterations.
• The approval is supported by findings from the LIBRETTO-121 trial (NCT03899792).

Selpercatinib has received accelerated approval from the FDA for the treatment of pediatric patients aged 2 years and older with advanced or metastatic medullary thyroid cancer with a RET mutation, advanced or metastatic thyroid cancer with a RET fusion, and locally advanced or metastatic solid tumors with a RET gene fusion.¹

This marks the first approved targeted therapy for pediatric patients with RET gene alterations.

The drug’s efficacy was verified in the phase 1/2 LIBRETTO-121 study. In the trial, patients received 92 mg/m2 of selpercatinib orally twice daily until disease progression, unacceptable toxicity, or other reason for treatment discontinuation. Patients aged 2 to 20 with RET-activated locally advanced or metastatic solid tumors that were nonresponsive to available therapies or did not have standard systemic treatments available were evaluated.

The confirmed overall response rate (ORR) was 48% (95% CI, 28%-69%) as confirmed by blinded independence central review. The median duration of response (DOR) was not reached (95% CI, not evaluable [NE]-NE), and 92% of responders were still in response at 12 months.

In patients with RET-mutant medullary thyroid cancer (n = 14), the ORR was 43% (95% CI, 18%-71%), and among those with RET fusion-positive thyroid cancer, the ORR was 60% (95% CI, 26%-88%).

Thyroid cancer of a woman, medically 3D illustration, front view: © Axel Kock - stock.adobe.com

Regarding safety, the most common adverse events (AEs; ≥25%) were musculoskeletal pain, diarrhea, headache, vomiting, coronavirus infection, abdominal pain, fatigue, pyrexia, and hemorrhage. Grade 3 or 4 laboratory abnormalities observed in at least 5% of patients were decreased calcium, decreased hemoglobin, and decreased neutrophils.

The primary end points of phase 2 of LIBRETTO-121 are ORR and ORR based on response assessment in neuro-oncology.² Secondary end points included pharmacokinetics, investigator-assessed ORR, DOR, progression-free survival, overall survival, clinical benefit rate, and incidence of AEs.

Patients with a Karnofsky or Lansky score of at least 50, adequate laboratory levels, and evidence of an activating RET gene alteration were eligible for enrollment in the study. Those with uncontrolled cardiovascular disease, uncontrolled systemic infection, uncontrolled hyperthyroidism or hypothyroidism, or active malabsorption syndrome were not eligible for participation.

REFERENCES:

1. FDA grants accelerated approval to selpercatinib for pediatric patients two years and older with RET-altered metastatic thyroid cancer or solid tumors. News release. FDA. May 29, 2024. Accessed May 29, 2024. https://tinyurl.com/3ykektts

2. A study of oral LOXO-292 (selpercatinib) in pediatric participants with advanced solid or primary central nervous system (CNS) tumors (LIBRETTO-121). ClinicalTrials.gov. Updated March 7, 2024. Accessed May 29, 2024. https://clinicaltrials.gov/study/NCT03899792