Benjamin Besse, President-Elect of EORTC and Head of Clinical Research at Gustave Roussy, shared a post on LinkedIn:
“Why is everyone so obsessed with ivonescimab and other bispecific PD-(L)1/VEGF antibodies in lung cancer?
The selection of the HARMONi-6 overall-survival readout for the ASCO plenary session perfectly captures the level of expectation surrounding ivonescimab.
HARMONi-6 is a phase III, first-line study in advanced squamous NSCLC comparing ivonescimab plus chemotherapy with tislelizumab plus chemotherapy. The impressive improvement in PFS (the primary endpoint) was published in The Lancet in 2025: 11.1 versus 6.9 months (HR 0.60, 95% CI 0.46–0.78; one-sided p<0.0001).
Anti-angiogenesis matters in squamous disease. However, excessive efficacy against centrally located lung tumors (typical for squamous) may result in cavitation and an increased risk of bleeding. Consequently, bevacizumab development was halted in squamous NSCLC after an early phase II study in which 4 of 13 patients with squamous histology treated with paclitaxel, carboplatin, and bevacizumab experienced serious or fatal pulmonary hemorrhage.
This limited experience led to the exclusion of squamous histology and of patients with centrally located tumors or major vessel involvement.
Bevacizumab, however, is approved in persistent, recurrent, or metastatic cervical cancer, the majority of which are squamous cell carcinomas.
And in NSCLC, the anti-VEGF story did not stop there. In REVEL, ramucirumab plus docetaxel improved survival overall, and subgroup analyses suggested a consistent benefit in both squamous and non-squamous disease, without an apparent increase in hemorrhagic events among patients with squamous histology.
In the era of immunotherapy, Lung-MAP S1800A showed that the addition of ramucirumab to pembrolizumab in pretreated patients appeared to derive most of its benefit from the squamous population (OS HR 0.43 versus 0.95 in non-squamous disease).
Bispecific PD-(L)1/VEGF antibodies display adverse events consistent with inhibition of both pathways, particularly hypertensio, bleeding and proteinuria for VEGF. In HARMONi-6, the rate of severe hemorrhage was low.
Too low? The incidence appears somewhat higher in the early data reported for competing PD-(L)1/VEGF bispecific antibodies. We should wait for the results of the global sister study, HARMONi-3, before making any definitive judgment on the hemorrhagic safety profile.
The OS data released today showed an improvement from 23.7 to 27.9 months (HR 0.66, 95% CI 0.50–0.87; one-sided p=0.0017). Worth a plenary presentation?
Twenty years after bevacizumab first changed the lung cancer conversation, we may simply be rediscovering that angiogenesis inhibition still matters-especially in squamous disease.”
Other articles about Lung Cancer on OncoDaily.