A phase 1/2, open-label study evaluating the efficacy, safety, and pharmacokinetics of luveltamab tazevibulin in infants and children < 12 years of age with <i>CBFA2T3::GLIS2</i> acute myeloid leukemia.
Bibliographic record
Abstract
TPS10074 Background: CBFA2T3::GLIS2 -rearranged acute myeloid leukemia (AML) is a rare subtype of AML occurring exclusively in very young children and is associated with poor prognosis ( < 15% 5-year event-free survival [EFS]) with best-available multi-agent chemotherapy. Luveltamab tazevibulin (luvelta) is an anti–FRα-targeting antibody-drug conjugate with a stable cleavable linker and a 3-aminophenyl hemiasterlin warhead (DAR = 4), which induces cytotoxic and immunologic cell death. CBFA2T3::GLIS2 AML uniquely expresses high cell surface levels of the FRα, suggesting that FRα-targeted therapies may be effective. Preclinical studies have demonstrated that treatment with luvelta can result in leukemia clearance. Preliminary safety and efficacy data from 25 children with relapsed/refractory CBFA2T3::GLIS2 AML treated with luvelta via compassionate use are promising [Williams, et al, BLOOD 2023, 142 (1): 4295]. Methods: This registration-enabling phase 1/2 study (clinicaltrials.gov NCT06679582) will investigate the pharmacokinetics, safety and preliminary efficacy of Luvelta in relapsed or refractory children with CBFA2T3::GLIS2 AML and ≥5% bone marrow (BM) involvement by morphology. The CBFA2T3::GLIS2 fusion will be confirmed at Foundation Medicine by next generation sequencing (NGS). The trial will open in up to 35 centers across US, Europe, Canada and Australia and is actively enrolling. The initial part of the trial will test luvelta monotherapy at 3.5 mg/kg or 4.3 mg/kg administered IV every 2 weeks in a 28-day cycle. Bayesian sequential monitoring is used for safety monitoring. The study committees will review the data to identify the recommended phase 2 dose of luvelta which will then be tested in the second part of the trial. Children who achieve BM morphological complete response (CR) may proceed to allogeneic hematopoietic stem cell transplantation (HSCT) or continue single-agent luvelta for up to 2 years at the investigators’ discretion. Patients without CR after 2 cycles of luvelta monotherapy may add chemotherapy (cytarabine +/- fludarabine or azacytidine) in cycle 3 and beyond. Post-HSCT maintenance therapy with luvelta monotherapy is also allowed for up to 2 years. The primary endpoint is morphologic CR defined as < 5% AML blasts in BM with absolute neutrophil recovery to > 1000 and platelets > 100,000 and absence of extramedullary disease. Secondary endpoints include PK levels and assessment of anti-drug antibody formation, safety, EFS and overall survival. Rates of measurable residual disease-negative CR and FRα antigen levels pre- and post-luvelta will also be explored. Clinical trial information: NCT06679582 .
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 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".