Drug companies have wagered billions on bispecific antibody drugs ever since one of them, ivonescimab, a PD-1 and vascular endothelial growth factor (VEGF) combination, beat Keytruda in a lung cancer trial in 2024.
That win spurred a wave of deals, and recent data from a China-based phase 3 trial for ivonescimab seemed to validate the hype. In the study, the drug, developed by Akeso and licensed to Summit Therapeutics, cut the risk of death in lung cancer by 34% compared to standard chemotherapy plus a PD-1 inhibitor.
But trial data may not tell the full story of the treatment, and companies could be missing a better opportunity for VEGF bispecifics, 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,” Chowdhury said.
Evidence from past trials suggests that the mechanism may have a better payoff in other types of cancer, including liver tumors like hepatocellular carcinoma, which rely more heavily on the VEGF protein pathway, he said. Gastric cancers could be another promising target.
A complicated picture in lung cancer
It’s not surprising that lung cancer has garnered the most attention from bispecific developers.
“Lung cancer is probably one of the biggest markets out there in terms of dollar value,” Chowdhury said.
Drugmakers including BioNTech, Merck & Co. and Pfizer are all chasing a lung cancer indication for their investigational PD-1/VEGF bispecifics. But while trial results look favorable, there is reason for skepticism, Chowdhury said. For example, Chinese trials enroll a different patient mix than many Western trials.
“In China, a lot of these trials have enrolled patients who are almost exclusively male and ex or current smokers,” Chowdhury said.
In the phase 3 ivonescimab trial, about 93% of patients were male, with a median age of 64. Lung cancer patients in the U.S. may include a more mixed demographic that skews younger, so results may look different, he noted.
Indeed, more data on ivonescimab released in May 2025 delivered a split verdict. The drug demonstrated positive progression-free survival data in topline results from Summit’s phase 3 global clinical trial, but a 21% reduction in death risk compared to chemotherapy alone wasn’t statistically significant, and the study missed the mark on overall survival benefit.
“From my personal perspective, 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 or not,” Chowdhury said.
Even if ivonescimab doesn’t deliver on its full promise in global lung cancer populations, bispecifics may still have something to offer in other cancer types.
Companies are starting to broaden out, launching large phase 3 trials outside of lung cancer, Chowdhury said. Ivonescimab is also in phase 3 testing for colorectal cancer. BioNTech’s BNT327, which targets VEGF and PD-L1 instead of PD-1, is not only being tested in a partnership with Bristol Myers Squibb in lung cancer, but in several other tumor types, including breast, colorectal and liver.
“There are two ways to look at it,” Chowdhury said. “One could be that they're looking at the lung evidence as convincing enough that it's safe now to launch trials in other indications. The other way to look at this is perhaps some of these companies share the skepticism that we've been talking about, and so it's really a way to derisk these large dollar value acquisitions.”
