Yet again Lenvima fails to Leap

Merck & Co has made much of combining Keytruda with Eisai’s Lenvima in front-line kidney cancer, but moving the combo beyond this approved use has proved impossible. Today saw two more Keytruda plus Lenvima trials flunk, both in lung cancer, taking the litany of setbacks to seven failed trials of this combo in the so-called Leap programme. Merck said Leap-008, a second-line NSCLC trial, failed versus docetaxel, while the front-line Leap-006 study of a Keytruda/Lenvima/chemo triplet failed versus Keytruda plus chemo, an approved standard of care. The results must surely have been expected given the abysmal failure in 2021 of Leap-007, a front-line NSCLC trial in patients whose tumours expressed PD-L1 at ≥1%, where Keytruda recipients actually lived longer, on average, than those given the Merck drug plus Lenvima. Possible phase 3 readouts this year include Leap-001 in endometrial carcinoma, but given the precedent hopes surely can’t be high.  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 carcinomaVs chemo, ends Nov 2023Leap-014*1st-line oesophageal carcinomaVs Keytruda + chemo, ends Dec 2025Leap-015*1st-line gastroesophageal adenocarcinomaVs chemo, ends Feb 2026Leap-012**Non-metastatic hepatocellular carcinomaVs TACE, ends Jun 2028Note: *chemo-containing triplet; **also contains TACE. Source: OncologyPipeline & company announcements.