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

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.

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Journal
Journal of Clinical Oncology
Published
2026-10-14
DOI
https://doi.org/10.1200/jco-25-03013
Primary Topic
Thyroid Cancer Diagnosis and Treatment
Type
article
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0.00

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article

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

Steven G. DuBois, Olivera Grbovic-Huezo, Tanya Carens Watt, Frank M. Balis et al.
Journal of Clinical Oncology
Thyroid Cancer Diagnosis and Treatment
article

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

Steven G. DuBois, Olivera Grbovic-Huezo, Tanya Carens Watt, Frank M. Balis, SUBHA SURIYAPPERUMA, Stephanie Fetzko, Daniel A. Morgenstern, Atsushi Manabe, Fariba Navid, Alberto S. Pappo, Birgit Geoerger, Antoinette Catherine Anazodo, Raquel Hladun Alvaro, Ayumu Arakawa, Cornelis Martinus van Tilburg, Leo Mascarenhas, Charlotte Rigaud, Douglas S. Hawkins, Dan Liu, Karsten Nysom, Theodore Willis Laetsch, Hyoung Jin Kang, Jennifer A. Wright, Patrick M. Peterson, Adrienne M. Gilligan, Michela Casanova, Catherine Albert, David Ziegler, Nivedita Sharma, Martin Campbell, Lorena Valero, Samara Potter
article en

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.

Journal of Clinical Oncology
University of Southern California (US), St. Jude Children's Research Hospital (US), Children's Hospital of Philadelphia (US), Children's Hospital of Los Angeles (US), Seoul National University (KR), Eli Lilly (United States) (US), German Cancer Research Center (DE), University of Toronto (CA), Hokkaido University (JP), Heidelberg University (DE), Hospital for Sick Children (CA), University Hospital Heidelberg (DE), Seoul National University Children's Hospital (KR), National Center for Tumor Diseases (DE), Hopp Children's Cancer Center Heidelberg (DE), Sydney Children's Hospital (AU), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US), Deutsches Konsortium für Translationale Krebsforschung (DE), University of Pennsylvania (US)
Eli Lilly and Company
Good health and well-being
Openalex Percentile: Top 11%
Thyroid Cancer Diagnosis and Treatment
DOIOpen Access PDFOpenAlex
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