MSD (Merck & Co) and Eisai have suffered a setback as the Phase III LEAP-015 trial evaluating Keytruda (pembrolizumab) and Lenvima (lenvatinib) combination therapy in patients with gastroesophageal adenocarcinoma failed to meet one of its dual primary endpoints.
The Phase III study (NCT04662710) investigated the safety and efficacy of using Keytruda and Lenvima in addition to chemotherapy as a first-line treatment for locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastroesophageal adenocarcinoma. Although the trial did achieve one of its dual primary endpoints by showing improvement in progression-free survival (PFS), it failed to elicit the same statistically significant response in overall survival (OS), the trial’s other primary endpoint.
Phase III LEAP-015 trial results
MSD and Eisai did not disclose the detailed results, choosing to unveil these at “an upcoming medical meeting”. Eisai’s Senior VP of Oncology Global Clinical Development, Dr Cornia Dutcus, did note that in addition to the PFS, an improvement in objective response rate (ORR) was also seen in the Keytruda, Lenvima and chemotherapy combination group of patients.
The open-label LEAP-015 trial enrolled about 880 patients who either received Keytruda, Lenvima, and chemotherapy combination or chemotherapy alone.
Mixed overall results for the Keytruda and Lenvima combo
The companies were quick to add that the results from the LEAP-015 study “do not affect the current approved indications for Keytruda plus Lenvima or other ongoing trials from the LEAP clinical program”. MSD and Eisai are assessing the combination therapy across various solid tumor indications, including endometrial carcinoma, hepatocellular carcinoma, melanoma, non-small cell lung cancer, and renal cell carcinoma.
While the mixed results from the LEAP-015 study may end up in the win column of the LEAP program. This includes the Phase III LEAP-012 trial (NCT04246177), where early results showed “statistically significant, clinically meaningful improvement in PFS and an early trend toward improvement in OS” in patients with intermediate-stage hepatocellular carcinoma (HCC).
LEAP program has had a string of failures including LEAP-006 (NCT03829319) and LEAP-008 (NCT03976375) trials where the Keytruda and Lenvima combination therapy failed to show significant improvement in certain types of metastatic non-small cell lung cancers. In August 2023, MSD and Eisai suspended the Phase III LEAP-010 study after an independent analysis showed that the trial was unlikely to meet its primary endpoints of OS, PFS and ORR.
Keytruda is the highest-grossing drug in MSD’s portfolio. It generated $7.4 billion in sales in Q3 last year, according to the company’s financials. MSD also has an extensive development program for its programmed cell death 1 (PD-1) inhibitor, exploring its use in multiple cancer indications either as a monotherapy or in combination with other cancer drugs.
Keytruda was first approved by the US Food and Drug Administration (FDA) in September 2014 for advanced melanoma. Since then it has been approved in just about 50 indications, either as a mono- or a combination therapy. The therapy has suffered some recent setbacks, with the US FDA’s Oncology Drugs Advisory Committee voting to limit the use of Keytruda along with other PD-1 inhibitors such as Bristol Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilimumab) in a September 2024 meeting.
