Merck, Eisai Post Back-to-Back Phase III NSCLC Failures for Keytruda-Lenvima Combo

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Pictured: Merck headquarters in California/iStock_Sundry Photography

Merck and Eisai on Friday suffered back-to-back late-stage defeats for their investigational combination regimen of Keytruda (pembrolizumab) and Lenvima (lenvatinib) in non-small cell lung cancer.

In the randomized and placebo-controlled Phase III LEAP-006 study, the combo therapy failed to significantly improve the study’s dual primary endpoints of progression-free survival (PFS) and overall survival (OS) when given as a first-line option. In an earlier interim analysis, the trial also found no statistically significant increase in objective response rate (ORR) among patients treated with the investigational regimen.

LEAP-006 compared the combination regimen against Keytruda alone, and all 748 enrolled patients were given background treatment with pemetrexed and platinum-based chemotherapy.

Meanwhile, the randomized and open-label Phase III LEAP-008 trial assessed the Keytruda-Lenvima combo as a second-line treatment option for patients who had progressed on or after a platinum-based regimen and one prior line of anti-PD-1/PD-L1 immunotherapy. The study found that in this setting, Merck’s and Eisai’s combination therapy also did not lead to significantly better PFS and OS.

As in the case of LEAP-006, an earlier interim analysis of LEAP-008 did not detect significant benefit in ORR.

Both LEAP-006 and LEAP-008 enrolled patients with metastatic, non-squamous non-small cell lung cancer (NSCLC) for whom EGFR-, ALK- or ROS1-directed therapies were confirmed to be not indicated. The two studies also did not flag new safety signals of concern and the documented adverse events were consistent with what had been reported in previous studies.

The pharma partners are still conducting the full analysis of these two studies and will share complete data in the future, according to Friday’s announcement. The outcomes of LEAP-006 and LEAP-008 also do not affect the current approved indications—and other ongoing trials—for the combination regimen of Keytruda and Lenvima.

Friday’s dual defeats continue the losing streak for the Keytruda-Lenvima combo. In April 2023, Merck and Eisai were forced to discontinue the Phase III LEAP-003 study in unresectable or metastatic melanoma after the combination therapy failed to significantly and meaningfully improve OS.

Simultaneously, the partners reported that Keytruda plus Lenvima likewise failed the Phase III LEAP-017 trial in colorectal cancer.

A few months later, in August 2023 Merck and Eisai posted another defeat for the LEAP program, this time in metastatic or unresectable head and neck squamous cell carcinoma. While Keytruda plus Lenvima led to significant improvements in PFS, the combo ultimately fell short of its bar for OS.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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