Is Selpercatinib Safe, Effective for Children With RET-altered Solid Tumors?

The FDA granted accelerated approval to selpercatinib for pediatric patients 2 years of age and older with RET-alterations. It is designed to block the primary driver of tumor growth in certain cancers.

The findings:

The Food and Drug Administration granted accelerated approval to selpercatinib (Retevmo®, Lilly), a targeted cancer therapy for pediatric patients 2 years of age and older with RET alterations. A prescription oral therapy, selpercatinib is designed to block the primary driver of tumor growth in certain cancers, such as thyroid cancers and rare soft tissue tumors caused by abnormal RET genes.

The decision was based on updated results from the LIBRETTO-121 clinical trial in which Children's Hospital of Philadelphia is a study site. These results, including more robust efficacy and pharmacokinetic data, continue to support the use of selpercatinib in pediatric and adolescent patients with RET-altered solid tumors. Selpercatinib's safety profile remains consistent with prior reports from adult trials.

Why it matters:

This is the first trial to assess the safety and efficacy of a selective RET inhibitor in pediatric and adolescent patients whose cancers are driven by a genomic alteration in the RET gene. RET is a gene that regulates cell growth. Mutations in the RET gene can cause cells to grow uncontrollably and develop into cancers called RET-positive tumors. RET mutations are rare, but occur in several different types of cancers, including thyroid cancers and some soft tissue tumors in children, and a form of lung cancer in adults.

These same cancers can be driven by mutations in other genes. This FDA approval highlights the importance of genetic testing of cancers to identify the driver of each patient's tumor. This allows precision medicine — using a medication that most specifically targets the driver of each patient's tumor — to limit the side effects of treatment.

Selpercatinib is a highly selective and potent central nervous system-penetrant oral RET inhibitor, designed to slow or stop the overproduction of RET in these tumorous cells. It was previously granted accelerated approval for RET-driven thyroid cancer in adult and adolescent patients, as well as lung or other solid tumors in adult patients.

Who conducted the study:

Pediatric Oncologist Theodore Laetsch, MD, co-director of the CHOP Center for Precision Medicine for High-risk Pediatric Cancer, leads the LIBRETTO-121 clinical trial at CHOP and is also the global PI for the international, single-arm, multicenter Phase I/II clinical trial.

How they did it:

The primary objectives were to evaluate safety and dose-limiting toxicities of selpercatinib for pediatric and young adult patients in Phase I and determine the overall response rate and duration of response in Phase II. The efficacy population included 25 patients ages 2 to 20 with advanced RET-altered solid tumors non-responsive to available therapies or with no standard systemic curative therapy available.

Patients received selpercatinib orally twice daily, until disease progression, unacceptable toxicity, or other reason for discontinuing treatment. The confirmed overall response rate was 48%, as determined by blinded independent review. The median duration of response was not reached, with 92% of responders remaining in response at 12 months. Durable responses were observed in pediatric and young adult patients with RET-mutant medullary thyroid cancer and RET-fusion thyroid cancer.

Quick thoughts:

"This FDA approval provides a new treatment option for the most common genetic mutation causing metastatic thyroid cancer in children," Dr. Laetsch said.

What's next:

Dr. Laetsch is partnering with Andrew Bauer, MD, co-director of the CHOP Thyroid Center Frontier Program, to open a CHOP-led study of selpercatinib in children, evaluating its use as frontline therapy for patients with RET-fusion thyroid cancer prior to the current standard of care, which is radioactive iodine treatment. "Our hope is that this combination will be more effective at inducing complete remission in our patients than either therapy alone," Dr. Laetsch said.

Where the study was published:

The research team presented updated study results in an abstract at the 2024 American Society of Clinical Oncology annual meeting.