ESMO Congress 2026

The anti-tumour value of blocking the VEGF pathway is backed by phase III evidence. In first-line unresectable hepatocellular carcinoma, the randomised phase 3 non-inferiority trial of lenvatinib (an inhibitor of VEGFR1-3, FGFR1-4, PDGFRα, RET and KIT) versus sorafenib randomly assigned 954 eligible patients, with a median survival time of 13.6 months in the lenvatinib arm ^[3]; among the systemic therapies approved for hepatocellular carcinoma based on phase III trials is also atezolizumab plus bevacizumab, a two-drug combination of a PD-L1 antibody and an anti-VEGF antibody ^[2]. Mechanistically, VEGF is a key regulator of physiological and pathological (including tumour) angiogenesis, with its effects mediated by the two receptor tyrosine kinases VEGFR-1 and VEGFR-2 ^[1]; it was purified as a secreted mitogen specific for vascular endothelial cells ^[5], its mRNA rises sharply within a few hours of hypoxia, and it is specifically expressed in glioblastoma cells in immediate proximity to necrotic foci ^[6], indicating that hypoxic tumours are the main setting where VEGF drives angiogenesis.

What is new at this meeting is not a specific trial readout, but a discussion by Funda Meric-Bernstam of MD Anderson on the rationale for combining ADCs with immunotherapy: ADCs may induce immunogenic cell death, release DAMPs and prime the tumour microenvironment, and may also increase PD-L1 expression and help overcome antigen heterogeneity; VEGF–PD-(L)1 bispecifics aim to reverse vascular immunosuppression and improve tumour immune access. The official ESMO post also named an investigational bispecific — the anti-PD-L1/VEGF-A pumitamig — as showing promise when combined with ADCs in advanced solid tumours. Notably, neither on-site post disclosed a specific trial name, tumour-type composition, sample size, or any efficacy or safety figures.

Relative to existing knowledge, this discussion pushes the IO plus anti-VEGF concept from two-drug combinations toward a single-molecule dual-target design, further layered with an ADC. Prior clinical evidence centred on the two-antibody regimen of atezolizumab plus bevacizumab, and on VEGFR TKIs such as lenvatinib ^[2][3]; pumitamig instead integrates PD-L1 and VEGF-A into one molecule and is combined with ADCs under the hypothesis that ADCs induce immunogenic cell death and upregulate PD-L1 expression, with the bispecific's two arms corresponding respectively to relieving vascular immunosuppression and blocking the PD-L1 pathway, linking classical VEGF biology ^[1][6] with immune modulation in a single framework.

The limitations are equally clear: the on-site posts contain no verifiable data, and the evidence strength, eligible population and safety of pumitamig plus ADCs remain undisclosed; the mechanistic statements are framed throughout with 'may', representing hypotheses yet to be validated, still a clear distance from the phase III evidence supporting atezolizumab+bevacizumab and lenvatinib ^[2][3].