The phase 3 LEAP-001 trial did not meet its primary end points of overall survival and progression-free survival.
Pembrolizumab (Keytruda) and lenvatinib (Lenvima) did not improve overall survival (OS) or progression-free survival (PFS) in the first line in patients with advanced or recurrent endometrial carcinoma whose disease is mismatch repair proficient (pMMR)/not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)/MSI-H, missing the dual primary end points of the phase 3 LEAP-001 study (NCT03884101).1
The results from the final analysis showed that pembrolizumab and lenvatinib did not show survival improvements compared with the standard-of-care platinum-based chemotherapy doublet of carboplatin plus paclitaxel. Regarding safety, the safety profile was consistent with the known profiles of the individual agents, and no new safety signals were identified.
“We remain confident in the proven benefit of [pembrolizumab] plus [lenvatinib] for the treatment of appropriate patients with certain types of previously treated advanced endometrial carcinoma based on results from the KEYNOTE-775/Study 309 trial [NCT03517449] and will continue to research the [pembrolizumab] plus [lenvatinib] combination in patients with other types of difficult-to-treat cancers,” said Gregory Lubiniecki, MD, vice president, global clinical development, Merck Research Laboratories, in a press release. “We are disappointed that the LEAP-001 trial did not reach its primary end points, as we had hoped to bring another potential treatment option to patients when first diagnosed with certain types of advanced or recurrent endometrial carcinoma.”
Currently, pembrolizumab and lenvatinib are indicated for the treatment of patients with advanced inoperable endometrial carcinoma that is pMMR or not MSI-H who have disease progression following prior systemic therapy. The combination is also indicated for first-line treatment of patients with advanced renal cell carcinoma.2
The combination is still being investigated for the treatment of hepatocellular carcinoma, head and neck cancer, gastric cancer, and esophageal cancer.1
“Results from the LEAP-001 trial underscore the challenges of treating patients with advanced or recurrent endometrial carcinoma in the first-line setting,” said Corina Dutcus, MD, senior vice president, oncology global clinical development lead at Eisai Inc, in a press release. “We remain optimistic about the clinical development program for [pembrolizumab] plus [lenvatinib] and are proud that the combination has become a standard of care option for patients with certain types of advanced or recurrent endometrial carcinoma whose disease has progressed following prior systemic therapy and will continue our efforts to contribute to these patients.”