Trial results for a Phase 3 study evaluating pembrolizumab (Keytruda) in combination with chemotherapy, with or without lenvatinib, for metastatic nonsquamous non-small cell lung cancer (NSCLC) were posted on ClinicalTrials.gov on 2025-02-21. The study, NCT03829319, found that the addition of lenvatinib did not significantly prolong progression-free survival (PFS), with a median PFS of 12.1 months for the lenvatinib arm compared to 9.5 months for the placebo arm.

Background

Metastatic nonsquamous non-small cell lung cancer (NSCLC) is an aggressive form of lung cancer that has spread to other parts of the body. It represents a significant clinical challenge, often requiring multi-modal treatment approaches to improve patient outcomes.

Trial design

The completed Phase 3 study (NCT03829319) enrolled 761 adult participants with metastatic nonsquamous non-small cell lung cancer. The trial assessed the safety and efficacy of a regimen combining pemetrexed + platinum chemotherapy + pembrolizumab, either with or without lenvatinib, as a first-line intervention. The primary hypothesis focused on whether the combination including lenvatinib would prolong Progression-free Survival (PFS) as assessed by blinded independent central review (BICR) per modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), compared to the regimen with a matching placebo.

Key results

The trial's primary hypothesis regarding Progression-free Survival (PFS) did not achieve statistical significance. For the Part 2 cohort, the median PFS was 12.1 months for the pembrolizumab + chemotherapy + lenvatinib group, compared to 9.5 months for the pembrolizumab + chemotherapy + placebo group. The Hazard Ratio (HR) for PFS was 0.88 (95% Confidence Interval [CI]: 0.74, 1.05), with a p-value of 0.07976.

Median Overall Survival (OS) was 21.8 months in the pembrolizumab + chemotherapy + lenvatinib group and 22.1 months in the pembrolizumab + chemotherapy + placebo group. The HR for OS was 1.05 (95% CI: 0.88, 1.26), with a p-value of 0.70818.

Objective Response Rate (ORR) per RECIST 1.1 was 57.1% for the pembrolizumab + chemotherapy + lenvatinib group and 50.7% for the pembrolizumab + chemotherapy + placebo group. The percent difference in ORR was 6.3% (95% CI: -2.8, 15.4), with a p-value of 0.08643. The median Duration of Response (DOR) was 1.6 months for both the pembrolizumab + chemotherapy + lenvatinib group and the pembrolizumab + chemotherapy + placebo group, with a full range reported.

Regarding safety, in Part 1 of the study, 2 participants in the pembrolizumab + chemotherapy + lenvatinib arm experienced a dose-limiting toxicity. A total of 13 participants experienced an adverse event, and 9 participants discontinued study drug due to an adverse event in this arm. In the larger Part 2 cohort, 372 participants in the pembrolizumab + chemotherapy + lenvatinib arm experienced an adverse event.

What this means

The trial results indicate that while the combination of pembrolizumab, chemotherapy, and lenvatinib showed numerically higher median PFS and ORR compared to the regimen with placebo, these differences did not reach statistical significance. The median overall survival was also comparable between the two arms. These findings suggest that adding lenvatinib to pembrolizumab and platinum-based chemotherapy may not provide a statistically significant clinical benefit in the first-line treatment of metastatic nonsquamous NSCLC, based on the primary endpoints evaluated in this study.

Source

The information for these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03829319, titled 'Safety and Efficacy Study of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) as First-line Intervention in Adults With Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-7902-006/E7080-G000-315/LEAP-006)', were posted on 2025-02-21 on clinicaltrials.gov.