Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and Eisai announced results from the Phase 3 LEAP-015 trial evaluating KEYTRUDA^® (pembrolizumab), Merck’s anti-PD-1 therapy, plus LENVIMA^® (lenvatinib), the orally available multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai, in combination with chemotherapy (KEYTRUDA plus LENVIMA-based regimen), for the first-line treatment of patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastroesophageal adenocarcinoma. At an interim analysis, the KEYTRUDA plus LENVIMA-based regimen demonstrated a statistically significant improvement in progression-free survival (PFS), one of the study’s dual primary endpoints, and objective response rate (ORR), a key secondary endpoint, compared to standard of care chemotherapy. The study continued, and at the final analysis, it did not meet its other primary endpoint of overall survival (OS). The safety profile of the KEYTRUDA plus LENVIMA-based regimen was consistent with that observed in previously reported studies evaluating the combination. A full evaluation of the data from this study is ongoing, and Merck and Eisai will present these results at an upcoming medical meeting.

“Locally advanced unresectable or metastatic gastroesophageal adenocarcinoma remains a challenging disease to treat and a leading cause of cancer death worldwide,” said Dr. Gregory Lubiniecki, Vice President, Global Clinical Development, Merck Research Laboratories. “These study results add to our understanding of this combination and will inform our future research as we strive to improve outcomes for more patients with cancer.”

“Gastric and gastroesophageal cancers continue to present challenges due to their heterogeneity and generally poor prognoses,” said Dr. Corina Dutcus, Senior Vice President, Oncology Global Clinical Development Lead at Eisai Inc. “While the LEAP-015 trial did not show a statistically significant increase in overall survival, we were pleased to observe an improvement in progression-free survival and objective response rate for patients treated with KEYTRUDA plus LENVIMA in combination with chemotherapy. These results contribute to the scientific community’s collective understanding of these complex diseases and add to the body of knowledge in oncology research. We are deeply grateful to the patients, caregivers and investigators who participated in this study.”

KEYTRUDA plus LENVIMA is approved in the U.S., the EU, Japan and other countries for the treatment of advanced renal cell carcinoma (RCC) and certain types of advanced endometrial carcinoma. Lenvatinib is marketed as KISPLYX for advanced RCC in the EU. Merck and Eisai are studying the KEYTRUDA plus LENVIMA combination through the LEAP ( LE nvatinib A nd P embrolizumab) clinical program in hepatocellular carcinoma and esophageal cancer across multiple clinical trials.

In gastric cancer, KEYTRUDA is approved in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma based on OS and other data from the Phase 3 KEYNOTE-859 trial. KEYTRUDA is also approved in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma, whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response data from the Phase 3 KEYNOTE-811 trial. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

In esophageal cancer, KEYTRUDA is approved in combination with platinum- and fluoropyrimidine-based chemotherapy for the treatment of patients with locally advanced or metastatic esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation. This approval is based on OS and other data from the Phase 3 KEYNOTE-590 trial.

Results from the LEAP-015 trial do not affect the current approved indications for KEYTRUDA plus LENVIMA or other ongoing trials from the LEAP clinical program.