Pharma bets big on cancer bispecifics — but may be targeting the wrong tumour
Analysts warn that lung cancer focus could be obscuring stronger opportunity in liver and gastric tumours
Drugmakers have wagered billions of dollars on a new class of cancer drugs targeting two well-known biological pathways — PD-1 and VEGF — but analysts say the industry's fixation on lung cancer may be obscuring a more compelling opportunity elsewhere.
The rush into PD-1/VEGF bispecific antibodies was triggered by a landmark 2024 trial in which ivonescimab, developed by China's Akeso and licensed to Summit Therapeutics (SMMT), beat Merck & Co.'s (MRK) Keytruda in a lung cancer study. A subsequent phase 3 trial conducted in China added to the enthusiasm, showing the drug reduced the risk of death by 34% compared with standard chemotherapy combined with a PD-1 inhibitor.
Yet that data may not tell the full story, according to Souro Chowdhury, a senior business analyst at Lifescience Dynamics. "There's a lot of excitement about their application in lung cancer, but that's not necessarily the right or the best indication for this type of drug," he said.
Chowdhury argues that the underlying biological mechanism — which includes blocking VEGF, a protein that promotes blood vessel growth in tumours — may be better suited to cancers that rely more heavily on that pathway, particularly hepatocellular carcinoma, the most common form of liver cancer, as well as gastric tumours.
Lung cancer's demographic problem
The appeal of lung cancer as a lead indication is not hard to understand. "Lung cancer is probably one of the biggest markets out there in terms of dollar value," Chowdhury said. BioNTech (BNTX), Merck and Pfizer (PFE) are all running trials of investigational PD-1/VEGF bispecifics in lung cancer patients.
But the Chinese trial data underpinning much of the sector's optimism raises questions about how broadly applicable the results will be. The ivonescimab phase 3 study enrolled a population that was approximately 93% male, with a median age of 64, and composed almost exclusively of current or former smokers. Lung cancer demographics in the US and Europe are more varied and skew younger, potentially altering outcomes.
Those concerns appeared to be borne out in data released in May 2025, when Summit reported a split verdict from its global phase 3 trial of ivonescimab: while the drug showed a positive effect on disease progression, a 21% reduction in the risk of death compared with chemotherapy alone fell short of statistical significance. "We need to see more data, and we also need to see some of these global trials read out over the next few years to really see whether this is applicable on a global stage," Chowdhury said.
Broadening the bet
The industry is beginning to hedge. Companies are launching large phase 3 trials in indications beyond lung cancer, with ivonescimab now in late-stage testing for colorectal cancer. BioNTech's pumitamig — which targets VEGF and PD-L1 rather than PD-1 — is being tested in partnership with Bristol Myers Squibb (BMY) in lung cancer, but also across breast, colorectal and liver tumours.
Chowdhury sees two interpretations of this trend. Either companies are sufficiently encouraged by the lung data to justify expanding into other tumour types, or they share the skepticism about lung cancer's promise and are seeking to derisk what have, in several cases, been large-dollar licensing transactions.
Either way, the coming years of readouts from global trials will be critical in determining whether PD-1/VEGF bispecifics live up to their billing — and in which patients they are most likely to do so.