Trial reportJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2025
Lenvatinib Plus Pembrolizumab, Pemetrexed, and a Platinum as First-Line Therapy for Metastatic Nonsquamous NSCLC: Phase 3 LEAP-006 Study.
Trial report in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03829319 (A Phase 3 Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Pemetrexed + Platinum Chemotherapy + Pembrolizumab), which is not on this map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 3 Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First-line Intervention in Participants With Metastatic Nonsquamous Non-small Cell Lung Cancer (LEAP-006)
Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Efficacy of PD-1/PD-L1 inhibitors combined with multi-targeted anti-angiogenic TKIs in advanced or metastatic NSCLC: A meta-analysis based on RCTs.Frontiers in oncology · 2026Pooled it
- A phase 2, open-label, single-arm study evaluating the combination of pembrolizumab, lenvatinib, carboplatin and pemetrexed in patients with metastatic non-small cell lung cancer harbouring targetable genomic alterations who progressed on standard tyrosine kinase inhibitors.Investigational new drugs · 2025Trial
- Lenvatinib Plus Pembrolizumab and Chemotherapy Versus Chemotherapy in Advanced Metastatic Gastroesophageal Adenocarcinoma: The Phase III, Randomized LEAP-015 Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Efficacy and safety of ICI-based triple combination therapy for gene-negative advanced lung adenocarcinoma.Oncology letters · 2026Article
- Long-Term Survival Heterogeneity Across PD-L1-Defined Subgroups in Pembrolizumab-Treated Non-Small-Cell Lung Cancer: A Model-Based Analysis.Pharmaceutics · 2026Article
- LEAP-006: limits and potential of integrating anti-angiogenic agents into first-line multimodal therapy for non-squamous non-small cell lung cancer.Journal of thoracic disease · 2025Article
- LEAP-008: pembrolizumab plus lenvatinib after immunotherapy in non-small cell lung cancer.Journal of thoracic disease · 2025Article
- Review
- Immune checkpoint inhibitor resistance in non-small cell lung cancer: limits of vascular endothelial growth factor inhibition and new directions.Journal of thoracic disease · 2025Article
- Next-generation immunotherapy: igniting new hope for lung cancer.Therapeutic advances in medical oncology · 2024Review
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Authors and funding
20 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionWe present the LEAP-006 (NCT03829319) phase 3 study evaluating the addition of lenvatinib to first-line pembrolizumab plus chemotherapy in metastatic nonsquamous NSCLC.
methodsAdults with previously untreated stage IV nonsquamous NSCLC without targetable genetic alterations were randomized 1:1 to lenvatinib 8 mg/d or placebo once daily plus pembrolizumab 200 mg every 3 weeks with pemetrexed and carboplatin or cisplatin for 4 cycles, followed by pembrolizumab (≤35 total cycles) and pemetrexed until disease progression or intolerable toxicity. Primary end points were progression-free survival and overall survival (OS). Part 1 was an open-label safety run-in of lenvatinib plus pembrolizumab and chemotherapy; part 2 was the randomized, double-blind study.
resultsParticipants (n = 748) were randomized to the lenvatinib (n = 375) or placebo (n = 373) arms. Median follow-up at final analysis (August 11, 2023) for OS was 36.8 months. Median (95% confidence interval [CI]) progression-free survival was 12.1 (10.4-14.1) versus 9.5 (8.3-10.7) months in the lenvatinib and placebo arms, respectively (hazard ratio, 0.88 [95% CI, 0.74-1.05]; 1-sided p = 0.07976). Median (95% CI) OS was 21.8 (18.6-24.0) versus 22.1 (19.7-24.2) months (hazard ratio, 1.05 [95% CI, 0.88-1.26]; 1-sided p = 0.70818). Grade 3 or higher treatment-related adverse events occurred in 69.7% and 55.6% of participants, respectively (grade 5, 5.6% versus 2.7%).
conclusionsAdding lenvatinib to first-line pembrolizumab plus chemotherapy did not improve efficacy versus pembrolizumab plus chemotherapy in stage IV nonsquamous NSCLC without targetable genetic alterations. There were no new safety signals. Pembrolizumab plus chemotherapy remains a standard of care for this population.
trial registrationClinicalTrials.gov (https://clinicaltrials.gov/), NCT03829319.
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