Randomized, double-blind, phase III LEAP-003 study of first-line lenvatinib plus pembrolizumab versus placebo plus pembrolizumab for unresectable or metastatic melanoma
Bibliographic record
Abstract
BACKGROUND: Lenvatinib plus pembrolizumab demonstrated antitumor activity in advanced melanoma after prior anti-programmed cell death protein or ligand 1 [PD-(L)1] therapy in LEAP-004. Here, we report results from LEAP-003 (NCT03820986) which evaluated first-line lenvatinib plus pembrolizumab versus placebo plus pembrolizumab in unresectable advanced melanoma. PARTICIPANTS AND METHODS: Participants with unresectable stage III or IV melanoma, previously untreated with PD-(L)1 inhibitors were randomly assigned 1 : 1 to pembrolizumab 200 mg intravenously every 3 weeks plus either lenvatinib 20 mg or placebo orally once daily. Dual primary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review and overall survival (OS). PFS was formally tested at the first interim analysis; OS at the final analysis. An external data monitoring committee regularly reviewed safety and efficacy. Three interim analyses and a final analysis were planned. RESULTS: Overall, 674 participants were assigned to lenvatinib plus pembrolizumab (n = 334) or placebo plus pembrolizumab (n = 340). Median PFS at first interim analysis was 8.4 months for lenvatinib plus pembrolizumab versus 4.0 months for placebo plus pembrolizumab [hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.59-0.88, P = 0.0008]. This benefit was not maintained at final analysis (HR 0.83, 95% CI 0.69-1.00). Median OS at final analysis was 25.8 months for lenvatinib plus pembrolizumab versus 39.5 months for placebo plus pembrolizumab (HR 1.20, 95% CI 0.97-1.48, P = 0.9521). Grade 3-5 treatment-related adverse events occurred in 58.7% of participants receiving lenvatinib plus pembrolizumab versus 29.0% receiving placebo plus pembrolizumab. CONCLUSIONS: Lenvatinib plus pembrolizumab did not provide additional benefit versus placebo plus pembrolizumab in participants with unresectable advanced melanoma. Thus, the trial was terminated early, and the third interim analysis became the final analysis. Immunotherapy remains the standard of care for advanced melanoma.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.005 |
| Insufficient payload (model declined to judge) | 0.012 | 0.002 |
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".