A curate's egg for Merck/Eisai's Leap

A partial clinical trial win might be no win at all if it includes a bust on overall survival, as Merck & Co and Eisai seemed to admit when toplining Leap-015, their latest study combining Keytruda with Lenvima. Leap-015 tested the doublet plus chemo versus chemo alone in front-line, HER2-negative gastroesophageal adenocarcinoma, and yielded a positive interim result for PFS, but at final analysis failed to show an OS benefit, the companies revealed on Friday. Rather than trumpet hopes of regulatory interactions, the groups merely thanked patients and said the data would add to the understanding of the combo and help inform future studies. Reasons explaining such caution include Lenvima's notorious toxicity, the availability in this setting of Keytruda plus chemo on the back of an OS benefit in Keynote-859 – though there are questions whether this will remain US-approved in PD-L1-negative patients – and the dismal record of other pivotal Keytruda/Lenvima combo trials. The companies did score a rare win last year in Leap-012 in liver cancer, but toxicity was high and no OS benefit has yet been shown. There has been no disclosure as to whether a filing backed by Leap-012 has been submitted. Selected Keytruda + Lenvima studiesTrialSettingResultKeynote-581/Clear1st-line renal cell carcinomaApproved useLeap-0071st-line PD-L1≥1% NSCLCFailed for OS vs KeytrudaLeap-0021st-line hepatocellular carcinomaFailed for OS & PFS vs LenvimaLeap-0031st-line melanomaFailed for OS vs KeytrudaLeap-0172nd-line colorectal cancerFailed for OS & PFS vs Stivarga or TAS-102Leap-0101st-line head & neck cancerFailed for OS vs KeytrudaLeap-006*1st-line NSCLCFailed for OS & PFS vs Keytruda + chemoLeap-0082nd-line NSCLCFailed for OS & PFS vs chemoLeap-011Cisplatin-ineligible PD-L1≥10% urothelial carcinomaFailed for OS & PFS vs KeytrudaLeap-0011st-line endometrial carcinomaFailed for OS & PFS vs chemoLeap-012**Non-metastatic hepatocellular carcinoma+ve for PFS vs TACE, awaiting OS readoutLeap-015*1st-line HER2-ve gastroesophageal adenocarcinomaFailed for OS vs chemoLeap-014*1st-line oesophageal carcinomaVs Keytruda + chemo, ends Dec 2025Notes: *chemo-containing triplet; **also contains TACE. Source: OncologyPipeline & company announcements.