Data from the first interim analysis of the Phase

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Data from the first interim analysis of the Phase 3 known as LEAP-012 show median progression-free survival of 14.6 mos. for the patients on the combination... versus 10 mos. for those in the placebo group.

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Thanks for the heads up.

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Llovet explained that the phase 3 LEAP-012 trial investigated the use of lenvatinib (Lenvima; Eisai and Merck), a tyrosine kinase inhibitor, and pembrolizumab (Keytruda; Merck Sharp and Dohme), an anti-PD-1 monoclonal antibody, in combination with TACE for intermediate-stage HCC.
https://www.pharmacytimes.com/view/phase-3-le...management

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Lenvatinib inhibits VEGF, Keytruda downregulates PD-1, TACE blocks angiogenesis all of which leronlimab also does. What that combo doesn't do is boost natural killer T-cells, downregulate tumor protectant Tregs with an M2 to M1 machrophage polarization shift or significantly cut down the trafficking of metastatic cells.

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Although OS data were still immature, the 2-year survival probability favored the combination arm, with a survival rate of 74.6% compared to 68.6% in the dual placebo arm. However, this difference did not reach statistical significance at the time of the interim analysis (HR: 0.80; P value: 0.086). The ORR was another notable result, with 46.8% of patients in the combination arm achieving a response compared to 33.3% in the placebo arm, underscoring the clinical activity of lenvatinib and pembrolizumab.

From a safety perspective, treatment-related AEs were observed more frequently in the combination arm, with 71% of patients experiencing grade 3/4 AEs compared to 31% in the placebo arm. Common AEs included hypertension, proteinuria, and elevated liver enzymes, which are consistent with the known safety profiles of lenvatinib and pembrolizumab. However, the toxicity was considered manageable, and only 8.4% of patients discontinued both drugs due to AEs, with a low incidence (1.7%) of grade 5 toxicity.

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6% increase in 2 year overall survival but a 40% increased chance of a severe adverse event. That may be worth it to some patients. Cancer takes advantage of much more of the immune response than those 3 drugs address. Leronlimab directly affects the overresponse of the immune system and may do better than all three combined without the severe adverse events.

I do find it interesting that they say that only 8.4% of patients discontinued both drugs but not how many discontinued one drug. If a large amount discontinued one drug then that 3 drug combo looks to be unviable.

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