Merck and Eisai Achieve up to 60.7% Progression-Free Survival in Phase 2 Trial of Pembrolizumab and Lenvatinib for Uveal Melanoma
Design and Significance of the Phase 2 PLUME Study
The Phase 2 PLUME study, led by the Institut Curie in France, evaluated the efficacy of a combination therapy of Keytruda (pembrolizumab, target: PD-1) from Merck (MRK) and Lenvima (lenvatinib, target: VEGFR/FGFR) from Eisai (ESAI) in patients with metastatic uveal melanoma. This trial represented a strategic attempt to maximize anti-cancer effects by combining immune checkpoint inhibition with the suppression of angiogenesis in the tumor microenvironment. Patient cohorts were divided based on prior Kimmtrak (tebentafusp, target: gp100/CD3) treatment history for precise analysis. This design is recognized as demonstrating the potential of precision medicine in the field of rare, refractory cancers by reflecting prior treatment history.
Different Survival Rates Based on Prior Treatment
According to the results presented at ESMO 2025, significant differences were observed in the primary endpoint of 27-week progression-free survival (PFS) based on the patients' prior treatment history. In Cohort 1 (HLA-A02:01 negative), which had no prior Kimmtrak (tebentafusp) treatment, the 27-week PFS was 31.8%, while in Cohort 2 (HLA-A02:01 positive), which had received prior Kimmtrak treatment, the PFS reached as high as 60.7%. This suggests that the immune activation induced by Kimmtrak treatment amplified the synergy between Keytruda and Lenvima, which is very encouraging data. This has garnered market attention as it presents a new clinical breakthrough for patients who previously had no suitable second-line treatment options after existing standard treatments.
Imaging Evaluation and Management of Adverse Events
The researchers used magnetic resonance imaging (MRI) and computed tomography (CT) to perform imaging-based response evaluations, carefully observing tumor shrinkage and disease control rates. The main adverse events observed in the clinical results were fatigue, hypertension, and diarrhea, which were consistent with the existing drug profiles, and no treatment-related deaths were reported. The ease of managing adverse events is a significant advantage for debilitated patients with metastatic disease to maintain long-term treatment. The encouraging tumor suppression effects confirmed by imaging and the manageable safety data will serve as a solid foundation for accelerating subsequent clinical trials and regulatory approval procedures.
Reshaping the Second-Line Treatment Market After Tebentafusp
The current metastatic uveal melanoma market is dominated by Kimmtrak (tebentafusp) from Immunocore (IMCR), which received FDA approval in January 2022 and generates approximately $400 million (USD) in annual sales. However, there is a significant unmet medical need because there are no approved treatments for patients whose disease progresses after Kimmtrak treatment. The success of the Keytruda and Lenvima combination therapy in this Phase 2 PLUME study demonstrates a strong commercial opportunity to gain a foothold in the second-line treatment market after Kimmtrak. This is expected to significantly extend the survival of patients with refractory cancers and herald a major change in the overall uveal melanoma treatment algorithm.
The uveal melanoma treatment market is a high-growth area, projected to grow from approximately $1.1 billion to $1.54 billion (USD) in 2025 to up to $2.7 billion (USD) in 2035. Immunocore's Kimmtrak, the current standard of care, generates annual sales of $400 million (USD) and dominates the market, but there is a lack of second-line treatment options for patients who relapse after treatment. The Phase 2 PLUME study, which showed that the Keytruda and Lenvima combination therapy achieved a 27-week progression-free survival (PFS) rate of 60.7% in patients who had received Kimmtrak treatment, is a significant event that has secured strong clinical evidence for gaining a foothold in the second-line treatment market. From the researchers' perspective, prior Kimmtrak treatment has scientifically proven that it synergizes with immune checkpoint inhibitors and multi-kinase inhibitors to reconstitute the tumor microenvironment. In the medium to long term, this combination therapy is expected to enter the second-line standard of care guidelines and maximize the value of Merck (MRK) and Eisai (ESAI)'s anti-cancer pipelines.
Source: ClinicalTrials.gov (api_ct)