MSD and Eisai’s combination of Keytruda (pembrolizumab) and Lenvima (lenvatinib) has shown a durable benefit of five years in a Phase III trial.

In KEYNOTE-775/ Study 309 (NCT03517449), MSD’s anti-PD-1 therapy plus Eisai’s oral multiple receptor tyrosine kinase inhibitor (TKI) bested chemotherapy in patients with advanced endometrial carcinoma who had received at least one prior platinum-based regimen in any setting.

MSD and Eisai presented the data at the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin, Germany. The data showed there was a five-year overall survival (OS) rate of 16.7% for the combination cohort compared to 7.3% for those treated with chemotherapy.

There was also a median OS of 18.0 months for Keytruda and Lenvima compared to 12.2 months for chemotherapy alone.

The Phase III randomised trial enrolled 827 patients, comprising 697 with cancer that was mismatch repair proficient (pMMR) and 130 with cancer that was mismatch repair deficient (dMMR).

In the five-year analysis, there were no new safety signals and the safety profile of the combination was consistent with previous studies, with treatment-related adverse events (TRAEs) occurring in 97.3% of patients on the combination compared to 93.8% of patients who received chemotherapy.

The original data from this study was announced in 2021, leading to the approval of the combination by the US Food and Drug Administration (FDA) for patients with advanced endometrial carcinoma that is pMMR or not microsatellite instability-high (MSI-H)

The combination has since been approved in the European Union (EU) and Japan for certain patients with advanced or recurrent endometrial carcinoma regardless of mismatch repair status.

Dr Corina Dutcus, senior vice president of Oncology Global Clinical Development Lead at Eisai, said: “The five-year results from KEYNOTE-775/Study 309 represent the longest reported follow-up for a trial evaluating an immunotherapy plus TKI combination in advanced endometrial carcinoma. These findings demonstrate the continued OS benefit observed with Keytruda plus Lenvima, further supporting the combination’s therapeutic value for patients facing this disease.”

ESCC trial miss

While this combination has shown benefit in endometrial cancer, it did not show benefit in oesophageal cancer. In the Phase III trial (NCT04949256), the combination failed to show benefit compared to Keytruda and chemotherapy as a first line treatment for metastatic oesophageal squamous cell carcinoma (ESCC).

Also announced at ESMO, the data showed a median OS of 18.0 months in the combination arm compared to 15.8 months in the Keytruda and chemotherapy cohort, missing the primary endpoint. The 12- and 24-month OS rates were 67% and 36% in the investigational arm compared to 63% and 31% in the control arm.