OR28-05 Selpercatinib in Pediatric and Adolescent Patients with RET-Altered Solid Tumors: Safety and Efficacy Results from the Phase 1/2 LIBRETTO-121 Study
Bibliographic record
Abstract
Abstract Disclosure: T.W. Laetsch: Advanced Microbubbles, AI Therapeutics, Bayer, Inc., ITM Oncologists, Jazz Pharmaceuticals, MassiveBio. R.H. Alvaro: None. D. Ziegler: Bayer, Inc., Amgen Inc, AstraZeneca, Merck, Novartis Pharmaceuticals, Day One Biopharmaceuticals, Accendatech, FivePhusion, Alexion Pharmaceuticals, Inc., Norgine. H.J. Kang: None. C. Albert: None. T.C. Watt: Ymabs Therapeutics Inc. S.L. Fetzko: None. A. Arakawa: None. K. Nysom: Bayer, Inc., Eli Lilly & Company. C. Rigaud: None. S. Suriyapperuma: Eli Lilly & Company. N. Sharma: Eli Lilly & Company. P. Peterson: Eli Lilly & Company. J. Wright: Eli Lilly & Company. D. Morgenstern: None. Introduction: Selpercatinib is a highly selective and potent oral RET inhibitor with CNS activity, approved for treatment of RET-altered tumors in patients (pts) aged ≥2 years. Here we report on the safety and efficacy of selpercatinib in pediatric and adolescent pts with RET-altered solid tumors from the LIBRETTO-121 study, with a median follow-up of 30 months. Methods: LIBRETTO-121 (NCT03899792) is a multicenter phase 1/2 trial in pts 0.5-21 yrs of age with advanced, RET-altered solid tumors. To confirm the recommended phase 2 dose (RP2D) for selpercatinib, dosing started at 92 mg/m2 BID, equivalent exposure to 160 mg BID in adults. The primary objectives were to evaluate safety and dose-limiting toxicities (DLTs) in phase 1 and determine the ORR per RECIST 1.1 by independent review in the phase 2 population. The secondary objectives were to determine the RP2D and investigator-assessed ORR, clinical benefit rate (CBR), DOR and PFS. Results: As of November 8, 2024, 36 pts aged 2-20 yrs were treated with selpercatinib. Tumor types included RET-mutant medullary thyroid cancer (MTC, n=15), RET fusion-positive papillary thyroid cancer (PTC, n=15) and other (n=6). The most common RET alterations were a M918T mutation (67% [10/15] of MTC pts) or NCOA4-RET fusion (47% [7/15] of PTC pts). Pts (n=36) treated at 92 mg/m2 (up to 160 mg BID) had a similar exposure as adults (n=667) treated with 160 mg BID at steady state on cycle 1 day 8. Time on selpercatinib ranged from 0.4 to 62.4 mo; 25 pts remained on treatment. There were no DLTs or treatment discontinuations due TEAEs; 8 pts (22%) experienced a dose reduction due to TEAEs. The most common TEAEs observed (≥30% of pts) were diarrhea, nausea, elevated AST, pyrexia, abdominal pain, elevated ALT, headache, cough, and vomiting. The most common TEAEs ≥ G3 included weight gain (11%), elevated ALT (8%), vomiting (8%), and anemia, constipation, hypertension, hypokalemia, and reduced neutrophil count, each occurring in 2 pts (6%). Investigator-assessed ORR among all pts was 36% (13/36) and 50% (18/36) had stable disease (SD), resulting in a CBR of 86% (31/36). Responses were durable, with a 24 mo DOR rate of 100% (95% CI: 100, 100). With a median follow-up of 30 mo, investigator-assessed mPFS among all pts has not yet been reached, and the 24 mo PFS rate was 86% (95% CI: 69%, 94%). Among pts with MTC, the ORR was 40% (6/15) and 53% (8/15) had SD, resulting in a CBR of 93% (14/15); 1 pt was unevaluable. In pts with PTC, the ORR was 33.3% (5/15) and 67% (10/15) had SD, resulting in a CBR of 100% (15/15). No MTC or PTC pts had PD through data cut off. Conclusions: With a median follow-up of 30 months selpercatinib continues to show durable efficacy in pediatric and adolescent pts with RET-altered thyroid cancer and is well tolerated with easily identifiable and manageable toxicities. These results further support the need to identify and target RET alterations with selpercatinib in pediatric and adolescent pts. Presentation: Monday, July 14, 2025
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".