LEAP-015
Trial question
What is the effect of lenvatinib plus pembrolizumab and chemotherapy in patients with advanced unresectable or metastatic gastroesophageal carcinoma?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
32.0% female
68.0% male
N = 880
880 patients (282 female, 598 male).
Inclusion criteria: adult patients with advanced unresectable or metastatic gastroesophageal carcinoma.
Key exclusion criteria: previous therapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma; major surgery in the last 28 days; radiotherapy in the last 14 days; known additional malignancy that is progressing or had required active treatment within the past 5 years; CNS metastases and/or carcinomatous meningitis; allogeneic tissue or solid organ transplant; perforation risk or significant gastrointestinal bleeding.
Interventions
N=443 lenvatinib plus pembrolizumab with chemotherapy (lenvatinib 8 mg once daily plus pembrolizumab 400 mg IV once every 6 weeks and investigator's choice of CAPOX once every 3 weeks or FOLFOX once every 2 weeks).
N=437 chemotherapy alone (investigator's choice of CAPOX once every 3 weeks or FOLFOX once every 2 weeks).
Primary outcome
Median progression-free survival in participants with PD-L1 combined positive score ≥ 1
7.3 months
6.9 months
7.3 months
5.5 months
3.6 months
1.8 months
0.0 months
Lenvatinib plus pembrolizumab with
chemotherapy
Chemotherapy
alone
Significant
increase ▲
Significant increase in median progression-free survival in participants with PD-L1 CPS ≥ 1 (7.3 months vs. 6.9 months; HR 1.33, 95% CI 1.11 to 1.61).
Secondary outcomes
Borderline significant increase in median overall survival in participants with PD-L1 CPS ≥ 1 (12.6 months vs. 12.9 months; HR 1.19, 95% CI 1 to 1.41).
Significant increase in median progression-free survival in the overall population (7.2 months vs. 7 months; HR 1.28, 95% CI 1.09 to 1.52).
Significant increase in objective response rate in the overall population (58% vs. 43.9%; AD 14.2%, 95% CI 7.7 to 20.6).
Safety outcomes
No significant difference in adverse events.
Conclusion
In adult patients with advanced unresectable or metastatic gastroesophageal carcinoma, lenvatinib plus pembrolizumab with chemotherapy was superior to chemotherapy alone with respect to median progression-free survival in participants with PD-L1 CPS ≥ 1.
Reference
Kohei Shitara, Sylvie Lorenzen, Jin Li et al. Lenvatinib Plus Pembrolizumab and Chemotherapy Versus Chemotherapy in Advanced Metastatic Gastroesophageal Adenocarcinoma: The Phase III, Randomized LEAP-015 Study. J Clin Oncol. 2025 May 31:JCO2500748. Online ahead of print.
Open reference URL