A groundbreaking development in cancer treatment has emerged with the introduction of bispecific antibodies targeting both PD-1 and VEGF cellular pathways, potentially offering superior results to Merck’s established immunotherapy drug Keytruda. The landscape of cancer therapeutics witnessed a significant shift in September when Summit Therapeutics and Akeso revealed clinical trial data showing their drug ivonescimab demonstrated remarkable efficacy against lung cancer, reducing progression risk by 50% compared to Keytruda.
This breakthrough has catalyzed widespread interest in PD-1/VEGF inhibitor development, with over a dozen pharmaceutical companies now pursuing similar treatments. These innovative drugs combine two established approaches: blocking blood vessel formation through VEGF inhibition and preventing cancer cells from evading immune system detection via PD-1 blockade.
Summit’s Chief Medical Officer Allen Yang described the findings as a “black swan event,” highlighting the long-sought-after nature of such results. The drug’s tetravalent structure enables enhanced binding to both target proteins, potentially explaining its superior performance over existing treatments.
However, some experts remain cautious. Bristol Myers Squibb’s Chief Medical Officer Samit Hirawat emphasized the need for more
comprehensive data, particularly regarding overall survival benefits. The trial’s limitation to Chinese patients has also raised questions about broader applicability.
Several companies have entered this promising field with unique approaches. BioNTech acquired rights to BNT327, while Merck secured a deal with Shanghai’s LaNova Medicines. Ottimo Pharma, led by former Seagen CEO David Epstein, is developing jankistomig, and Crescent Biopharma has designed a drug specifically to mirror ivonescimab’s effectiveness while improving manufacturing capabilities.
Safety considerations remain paramount, as VEGF inhibitors can cause serious side effects like hypertension and bleeding. The challenge with bispecific antibodies is that when such adverse effects occur, the entire treatment must be suspended, unlike with separate drugs that can be individually adjusted.
Looking ahead, crucial data is expected throughout 2025, including overall survival results from ivonescimab’s initial trial and outcomes from a global Phase 3 study in EGFR-mutated non-small cell lung cancer. The most definitive evidence may come from the Harmoni-3 trial, which will directly compare ivonescimab plus chemotherapy against Keytruda plus chemotherapy in over 1,000 lung cancer patients, with results anticipated in 2027.
The commercial implications are substantial, with analysts estimating a potential market worth approximately $20 billion. This represents a significant opportunity to challenge Keytruda’s dominance in cancer immunotherapy, where despite its success, many patients still don’t respond effectively to treatment.
The surge in development of these dual-targeting antibodies reflects a broader trend in cancer research, where combining therapeutic approaches in single molecules may offer advantages over traditional combination treatments. While early results are promising, the field awaits more comprehensive data to determine whether these new drugs will truly revolutionize cancer treatment or join the long list of attempted Keytruda challengers that fell short of expectations.
For patients, particularly those with limited response to existing immunotherapies, these developments offer hope for more effective treatment options. The medical community watches with interest as multiple clinical trials progress, potentially heralding a new era in cancer immunotherapy where dual-targeting approaches become the standard of care.