Safety and efficacy of selpercatinib in pediatric patients with RET-altered solid tumors: Updated results from LIBRETTO-121.
Bibliographic record
Abstract
10022 Background: Selpercatinib is a highly selective and potent CNS-penetrant oral RET inhibitor, approved for treatment of RET-driven thyroid cancer in adult and adolescent patients (pts), and lung or other solid tumors in adult pts. Here we present updated results from LIBRETTO-121, the first trial to assess the safety and efficacy of a selective RET inhibitor in pediatric and adolescent pts with RET-altered solid tumors. 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. Enrollment began in June 2019 and is ongoing. To confirm the recommended phase 2 dose for selpercatinib, dosing started at 92 mg/m2 BID, expecting to result in 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. Results: At the data cut-off (January 13, 2023), 27 pts aged 2-20 yrs were treated with selpercatinib. Tumor types included RET-mutant medullary thyroid cancer (MTC, n = 14), RET fusion-positive papillary thyroid cancer (PTC, n = 10), or other (n = 3). The most common RET alterations were a M918T mutation (71.4% [10/14] of MTC pts) or NCOA4-RET fusion (50% [5/10] of PTC pts). Pediatric and adolescent patients treated at 92 mg/m2 (up to 160 mg BID) had a similar exposure as adults treated with 160 mg BID at steady state on cycle 1 day 8. Time on selpercatinib ranged from 0.4 to 40.8 mo and 22 pts remain on treatment. There were no treatment discontinuations due to DLTs or TEAEs; 2 pts (7.4%) experienced a dose reduction due to TEAEs (elevated ALT and reduced neutrophil count). The most common TEAEs observed (≥25% of pts) were diarrhea, headache, coronavirus infection, nausea, vomiting, elevated ALT, elevated AST and pyrexia. The most common TEAEs ≥ G3 included constipation, reduced neutrophil count, vomiting and weight gain, each occurring in 2 pts (7.4%). One pt (age 15 yrs) experienced a TEAE ≥ G3 of epiphysiolysis, a risk for selpercatinib in this population based on pre-clinical data. In pts with RECIST measurable disease at baseline, the ORR was 83.3% (10/12), while 1 pt had stable disease (SD) and 1 pt had progressive disease (PD). Among pts with measurable disease at baseline, PTC pts had an ORR of 100% (5/5), and MTC pts had an ORR of 83.3% (5/6), while 1 MTC pt had SD. No PTC or MTC pts had PD. Responses were durable, with a 24 mo DOR rate of 100% (95% CI: NE, NE). With a median follow up of 18 mo, the mPFS among all pts has not yet been reached, and the 24 mo rate of PFS was 92.4% (95% CI: 73.0% - 98.1%). Conclusions: Selpercatinib’s safety profile remains consistent with prior reports from adult trials. These results, including more robust efficacy and PK data, continue to support the use of selpercatinib in pediatric and adolescent pts with RET-altered solid tumors. Clinical trial information: NCT03899792 .
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.004 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".