Adding the targeted therapy lenvatinib and the immunotherapy pembrolizumab to transarterial chemoembolization (TACE, a procedure that delivers chemotherapy directly into the blood vessels feeding a liver tumor) significantly extended progression-free survival compared with TACE plus two placebos, in adults with unresectable, non-metastatic, intermediate-stage hepatocellular carcinoma (the most common form of liver cancer), in the randomized, double-blind, phase 3 LEAP-012 trial (ClinicalTrials.gov NCT04246177; first interim results published in The Lancet, DOI 10.1016/S0140-6736(24)02575-3). Median progression-free survival was 14.6 months with the triple combination versus 10.0 months with TACE alone (hazard ratio 0.66; P=0.0002) — a real, statistically significant benefit. However, at this same interim analysis the trial’s co-primary endpoint of overall survival did NOT reach statistical significance (2-year overall-survival rate 75% versus 69%; hazard ratio 0.80; P=0.087), and subsequent reporting indicates the trial is being closed because a future analysis was judged unlikely to reach the pre-specified overall-survival threshold. This drug combination does not currently hold FDA approval for this indication in the United States (a related regulatory filing reportedly gained approval in China in 2025, not independently confirmed against a primary regulatory record).

The NCI-sponsored, phase 3 AMBASSADOR trial (Alliance A031501, ClinicalTrials.gov NCT03244384; primary publication DOI 10.1056/NEJMoa2401726) found that adjuvant pembrolizumab significantly extended disease-free survival compared with observation alone in adults with high-risk muscle-invasive or locally advanced urothelial (bladder) carcinoma following surgical removal of the bladder. The trial randomized 702 patients 1:1 to pembrolizumab (200 mg every 3 weeks for up to one year) or observation. Pembrolizumab does NOT currently hold FDA approval for this specific adjuvant indication — a different, related PD-1 inhibitor, nivolumab, received FDA approval for adjuvant muscle-invasive urothelial carcinoma in 2021, and AMBASSADOR’s own enrollment was closed early specifically because of that competing approval. Overall survival, the trial’s co-primary endpoint, was not yet statistically significant at the reported follow-up and remains an immature endpoint.