Trial results for the Phase 3 LEAP-015 study (NCT04662710) investigating lenvatinib plus pembrolizumab plus chemotherapy in participants with advanced/metastatic gastroesophageal adenocarcinoma were posted on ClinicalTrials.gov on 2025-11-28. The combination regimen demonstrated a median progression-free survival (PFS) of 7.2 months in all participants, compared to 7.0 months with chemotherapy alone, with a hazard ratio of 0.78 (95% CI: 0.66 to 0.92; p=0.0019).
Background
The LEAP-015 study investigated a combination therapy for advanced/metastatic gastroesophageal adenocarcinoma. This condition represents a significant challenge in oncology, necessitating effective treatment strategies.
Trial design
The LEAP-015 study (NCT04662710) was a Phase 3, randomized trial that enrolled 895 participants with advanced/metastatic gastroesophageal adenocarcinoma. The study compared the efficacy and safety of a combination regimen of lenvatinib, pembrolizumab, and chemotherapy (oxaliplatin, capecitabine, and leucovorin or levoleucovorin) against chemotherapy alone. Key efficacy outcomes included overall survival (OS) and progression-free survival (PFS) as assessed by blinded independent central review (BICR) per RECIST 1.1, in both the overall population and in participants with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1.
Key results
The trial results included both safety run-in data and efficacy outcomes from Part 2 of the study.
For the safety run-in phase (Part 1), 2 participants experienced dose-limiting toxicities (DLTs). A total of 15 participants experienced adverse events (AEs), with 5 participants discontinuing study treatment due to an AE.
In Part 2, key efficacy outcomes were assessed:
- Overall Survival (OS) in Participants with PD-L1 CPS ≥1: The median OS was 12.6 months for the lenvatinib + pembrolizumab + chemotherapy group and 12.9 months for the chemotherapy group. The hazard ratio (HR) was 0.84 (95% Confidence Interval [CI]: 0.71 to 1.0), with a p-value of 0.0244.
- OS in All Participants: The median OS was 13.1 months for the lenvatinib + pembrolizumab + chemotherapy group and 13.0 months for the chemotherapy group. The HR was 0.87 (95% CI: 0.75 to 1.01), with a p-value of 0.033.
- Progression-Free Survival (PFS) in Participants with PD-L1 CPS ≥1: The median PFS was 7.3 months for the lenvatinib + pembrolizumab + chemotherapy group and 6.9 months for the chemotherapy group. The HR was 0.75 (95% CI: 0.62 to 0.9), with a p-value of 0.0012.
- PFS in All Participants: The median PFS was 7.2 months for the lenvatinib + pembrolizumab + chemotherapy group and 7.0 months for the chemotherapy group. The HR was 0.78 (95% CI: 0.66 to 0.92), with a p-value of 0.0019.
- Objective Response Rate (ORR) in Participants with PD-L1 CPS ≥1: The ORR was 59.5% for the lenvatinib + pembrolizumab + chemotherapy group. The difference in percentage for ORR between groups was 14.3% (95% CI: 6.9 to 21.5), with a p-value of 0.0001.
- ORR in All Participants: The difference in percentage for ORR between groups was 14.2% (95% CI: 7.7 to 20.6), with a p-value of 0.0001.
What this means
The results from the LEAP-015 trial indicate that the combination of lenvatinib, pembrolizumab, and chemotherapy significantly improved progression-free survival and objective response rates compared to chemotherapy alone in patients with advanced/metastatic gastroesophageal adenocarcinoma. While the median overall survival showed numerical improvements, the hazard ratios for PFS and the significant differences in ORR suggest a meaningful clinical benefit for this challenging cancer. These findings provide important data for clinicians considering treatment options for this patient population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04662710, titled "Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) Plus Chemotherapy in Participants With Advanced/Metastatic Gastroesophageal Adenocarcinoma (MK-7902-015/E7080-G000-321/LEAP-015)," were posted on 2025-11-28 on clinicaltrials.gov.