The next phase of immuno-oncology development may be shaped by PD-(L)1×VEGF bispecific antibodies, which are engineered to combine immune checkpoint inhibition and anti-angiogenic therapy into a single molecule, according to a May 28 article. These assets have gained significant attention in the biopharma industry, with high-value deals such as Akeso’s out-licensing of ivonescimab to Summit Therapeutics for up to $5 billion and Bristol Myers Squibb’s $11.1 billion partnership with BioNTech for pumitamig.
Consultants at Lifescience Dynamics said that while most clinical trials so far have focused on lung cancer, other cancers may offer more potential for this class of drugs. "These antibodies target both immune checkpoints and angiogenesis—the formation of new blood vessels to provide nutrients and oxygen to cancer cells, enabling their growth and spread. Thus, in cancers where these processes are intertwined, such as hepatocellular carcinoma, PD-(L)1×VEGF bispecifics could be a one-two punch that knocks down these hard-to-treat malignancies," the consultants said.
Early-stage studies in China have shown high response rates and encouraging progression-free survival data in lung cancer patients treated with PD-(L)1×VEGF bispecifics. For example, the Phase 3 HARMONi-6 study found that ivonescimab plus chemotherapy led to a progression-free survival advantage compared with tislelizumab plus chemotherapy. However, larger global trials have yet to demonstrate clear overall survival benefits required by regulators such as the U.S. Food and Drug Administration or European Medicines Agency.
Summit Therapeutics recently announced that its Biologics License Application for ivonescimab plus chemotherapy has been accepted by the FDA, with an action date set for November 14. Meanwhile, some recent trial results did not meet statistical significance for progression-free survival at interim analysis stages.
Despite mixed results in lung cancer indications so far, several companies are now investigating PD-(L)1×VEGF bispecifics in other cancers including colorectal, biliary tract, pancreatic and triple-negative breast cancers through ongoing Phase 3 studies primarily in China. The success of atezolizumab plus bevacizumab as frontline therapy for unresectable hepatocellular carcinoma provides precedent supporting further exploration of this drug class outside lung cancer.
The article concludes that future value from PD-(L)1×VEGF bispecifics may depend on targeting tumors where angiogenesis is critical rather than focusing solely on lung cancer indications.
