Pembrolizumab Plus Lenvatinib Phase 3 Melanoma Trial Discontinued

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Pharmaceutical companies Merck and Eisai recently announced the discontinuation of the randomized, placebo-controlled, phase 3 LEAP-003 trial (NCT03820986)evaluating the safety and efficacy of pembrolizumab combined with lenvatinib for the treatment of unresectable or metastatic melanoma in adults.¹ Both companies noted that the decision to discontinue the trial is based on the recommendation from an independent data monitoring committee that determined pembrolizumab plus lenvatinib did not achieve an improvement in one of the primary dual endpoints of overall survival when compared to pembrolizumab alone.

During an earlier interim analysis, LEAP-003's other dual primary endpoint of progression-free survival demonstrated a statistically significant improvement in the pembrolizumab plus lenvatinib arm compared to the pembrolizumab plus placebo arm. Overall, the safety profile of pembrolizumab plus lenvatinib was consistent was previously reported data. Merk and Eisai will work with the investigators to share their results with the scientific community. Additionally, there is an ongoing full evaluation of the data, including pre-planned key subgroup analyses.

Key secondary endpoints include objective response rate and duration of response. The study enrolled 674 patients who were randomized 1:1 to receive:

• Pembrolizumab (200 mg intravenously on day 1 of each 3-week cycle) plus lenvatinib (20 mg orally once daily); or
• Pembrolizumab (200 mg intravenously on day 1 of each 3-week cycle) plus placebo via oral capsule daily

Pembrolizumab was administered for up to 35 cycles (approximately 2 years) or until protocol-specified discontinuation criteria were met. After completing 2 years of combination therapy, lenvatinib may have been administered as a single agent until protocol-specified discontinuation criteria were met.

Last week, the phase 2 KEYNOTE-695 trial (NCT03132675) evaluating the efficacy of the combination of interleukin 12 encoding plasmid tavokinogene telseplasmid (TAVO-EP; OncoSecMedical) plus intravenous pembrolizumab did not reach its primary endpoints. Study participants had to be diagnosed with unresectable or metastatic melanoma, stage III/IV, who were progressing on either pembrolizumab or nivolumab (Opdivo). Patients in the trial had confirmed disease progression after at least 12 weeks of exposure to immediate prior anti-PD-1 antibody therapy.

Reference

1. Merk and Eisai provide update on phase 3 trials of Keytruda (pembrolizumab) plus Lenvima (lenvatinib) in certain patients with advanced melanoma (LEAP-003) and metastatic colorectal cancer (LEAP-017). Published April 7, 2023. Accessed April 12, 2023. https://www.businesswire.com/news/home/20230405005809/en/Merck-and-Eisai-Provide-Update-on-Phase-3-Trials-of-KEYTRUDA%C2%AE-pembrolizumab-Plus-LENVIMA%C2%AE-lenvatinib-In-Certain-Patients-With-Advanced-Melanoma-LEAP-003-and-Metastatic-Colorectal-Cancer-LEAP-017