Lenvima’s latest Leap falls short

Last year Merck & Co and Eisai got some rare good news with a Keytruda/Lenvima combo, with a progression-free survival win in the Leap-012 liver cancer trial – but on Wednesday the groups disclosed that the trial had failed on its overall survival co-primary endpoint. The study, which had been testing Keytruda plus Lenvima and transarterial chemoembolisation (TACE) in unresectable, non-metastatic hepatocellular carcinoma, will now be closed. Last year’s ESMO meeting heard that this regimen produced a “profound” difference on PFS versus TACE alone, but even at the time the partners appeared to be awaiting OS data before filing, against the backdrop of Lenvima’s known toxicities. The only comparable trial is the Emerald-1 study of AstraZeneca’s Imfinzi plus TACE and Avastin, but here only a PFS benefit versus TACE has been shown, with nothing said about OS. Leap-012 is the latest of many failures for Keytruda plus Lenvima, including in the Leap-002 trial in first-line unresectable liver cancer; more recently there have been disappointments in Leap-014 Leap-015, in front-line oesophageal carcinoma and gastroesophageal adenocarcinoma respectively. This week, meanwhile, a Lenvima/Welireg combo prevailed in the Litespark-011 trial in second-line renal cancer, but only so far on PFS. Selected Keytruda + Lenvima studiesTrialSettingResultKeynote-581/Clear1st-line renal cell carcinomaApproved useLeap-0011st-line endometrial carcinomaFailed for OS & PFS vs chemoLeap-0021st-line hepatocellular carcinomaFailed for OS & PFS vs LenvimaLeap-0031st-line melanomaFailed for OS vs KeytrudaLeap-006*1st-line NSCLCFailed for OS & PFS vs Keytruda + chemoLeap-0071st-line PD-L1≥1% NSCLCFailed for OS vs KeytrudaLeap-0082nd-line NSCLCFailed for OS & PFS vs chemoLeap-0101st-line head & neck cancerFailed for OS vs KeytrudaLeap-011Cisplatin-ineligible PD-L1≥10% urothelial carcinomaFailed for OS & PFS vs KeytrudaLeap-012*Non-metastatic hepatocellular carcinoma+ve for PFS vs TACE, but failed on OS & trial closed Oct 2025Leap-014**1st-line oesophageal carcinomaFailed for OS vs Keytruda + chemoLeap-015**1st-line HER2-ve gastroesophageal adenocarcinomaFailed for OS vs chemoLeap-0172nd-line colorectal cancerFailed for OS & PFS vs Stivarga or TAS-102Notes: *also contains TACE; **chemo-containing triplet. Source: OncologyPipeline & company announcements.