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Publications

Journal Article Ahead of print

PubMed: 42874021 DOI: 10.1200/JCO-25-03013

Selpercatinib in Pediatric and Adolescent Patients With RET-Altered Solid Tumors: Safety and Efficacy Results From the Phase I/II LIBRETTO-121 Study.

J Clin Oncol

Authors: Theodore W Laetsch, Hyoung Jin Kang, Michela Casanova, Antoinette Anazodo, Steven G DuBois, Atsushi Manabe, Fariba Navid, Alberto Pappo, Adrienne M Gilligan, Olivera Grbovic-Huezo, Dan Liu, Subha Suriyapperuma, Nivedita Sharma, Patrick Peterson, Jennifer Wright, Cornelis M van Tilburg, Daniel Morgenstern

Affiliations

  • Children's Hospital of Philadelphia/University of Pennsylvania, Philadelphia, PA.
  • Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul National University Children's Hospital, Seoul, Korea.
  • Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • Kids Cancer Centre, Sydney Children's Hospital, Sydney, NSW, Australia.
  • Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Department of Pediatrics, Harvard Medical School, Boston, MA.
  • Hokkaido University Graduate School of Medicine, Sapporo, Japan.
  • Children's Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, CA.
  • St Jude Children's Research Hospital, Memphis, TN.
  • Eli Lilly and Company, Indianapolis, IN.
  • Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
  • Department of Pediatric Oncology, Hematology, Immunology, and Pulmonology, Heidelberg University, Heidelberg Faculty of Medicine, Heidelberg University Hospital, Heidelberg, Germany.
  • Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
  • National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership Between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
  • The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.

Abstract

PURPOSE

Selpercatinib, a highly selective oral RET inhibitor with CNS activity, has previously demonstrated durable responses and an acceptable safety profile in adults with RET-driven cancers. Consequently, the safety and efficacy of selpercatinib were investigated in pediatric/adolescent participants.

METHODS

LIBRETTO-121 (ClinicalTrials.gov identifier: NCT03899792) was a multicenter phase I/II trial of selpercatinib in participants age 0.5-21 years with advanced, RET-altered solid tumors. In phase I, the primary end point was safety, including dose-limiting toxicities. In phase II, the primary end point was objective response rate (ORR) as determined by independent review committee (IRC) per RECIST v1.1. Key secondary end points included ORR by investigator, duration of response (DOR), progression-free survival, overall survival, safety, and pharmacokinetics.

RESULTS

As of November 8, 2024, 36 participants age 2-20 years were treated with selpercatinib. Tumor types included RET-altered medullary thyroid cancer (MTC, n = 15), RET fusion-positive papillary thyroid cancer (PTC, n = 15), and other (n = 6). The most common treatment-emergent adverse events were diarrhea, nausea, elevated AST, pyrexia, abdominal pain, elevated ALT, headache, cough, and vomiting. No treatment discontinuations due to treatment-related adverse events or new adverse drug reactions were observed. ORR by IRC was 53% (19/36; 95% CI, 36 to 70). For participants with MTC and PTC, ORR by IRC was 60% (9/15; 95% CI, 32 to 84) and 53% (8/15; 95% CI, 27 to 79), respectively. The 24-month DOR rate was 100% (95% CI, 100 to 100).

CONCLUSION

Selpercatinib showed durable efficacy in pediatric/adolescent participants with RET-altered thyroid cancer and was well tolerated, supporting targeting of RET alterations in pediatric/adolescent patients.

MeSH

Safety, Neoplasms, Thyroid Gland, Drug-Related Side Effects And Adverse Reactions, Adolescent, Thyroid Neoplasms, Therapeutics, Medical Oncology