The emerging field of dual-payload antibody-drug conjugates has reached a critical milestone with two companies now testing these next-generation cancer therapeutics in clinical trials. Innovent's IBI3020, which targets CEACAM5 and comprises two undisclosed payloads, has begun a first-in-human solid tumor study, marking the entry of dual-payload ADCs into clinical development.
Clinical Development Race
According to clinicaltrials.gov listings, Innovent's IBI3020 study began on April 29, 2025, and is currently recruiting patients. This positions the company just ahead of China's Chengdu Kanghong in the dual-payload ADC race. Chengdu Kanghong's TROP2-targeting KH815 was initially expected to become the first dual-payload ADC to enter clinical trials when its study appeared on clinicaltrials.gov in March with a planned April 30 start date. However, that study has yet to begin recruiting patients according to the registry.
Innovent had promised in March that IBI3020 would start phase 1 trials this year, fulfilling that commitment with the recent study initiation. The hot area of dual-payload antibody-drug conjugates only entered the limelight last year but now suddenly has not one but two clinical-stage assets.
Technical Challenges and Design Considerations
Little is known about each molecule's specific characteristics, making it difficult to gauge their potential without more detailed information. The design of dual-payload ADCs is thought to be more complex than simply attaching two payloads instead of one to a monoclonal antibody, suggesting significant technical challenges in their development.
Expanding Pipeline
The dual-payload ADC space includes additional players beyond the two companies currently in clinical trials. Callio has assets in this area that the group acquired from Hummingbird Bioscience. A growing cohort of companies suspects that two different warheads may be better than one on antibody-drug conjugates, with dozens of these next-generation ADCs currently in preclinical development.
Broader ADC Innovation
The clinical advancement of dual-payload ADCs occurs alongside other innovative ADC approaches entering human testing. Tagworks' TGW101, targeting the unusual TAG-72 antigen, features a controlled release mechanism in the tumor microenvironment that only activates once a small-molecule trigger molecule (TRG001) is added. This represents a departure from traditional ADCs where MMAE payload is released intracellularly in a random fashion.
Market Context
The dual-payload ADC development comes as many ADC companies pursue popular targets including EGFR, B7-H3, and TROP2. The clinical entry of these next-generation therapeutics represents a significant evolution in cancer treatment approaches, with companies betting that dual-payload strategies will provide superior therapeutic outcomes compared to traditional single-payload designs.
The successful initiation of clinical trials for dual-payload ADCs marks a pivotal moment in oncology drug development, as the field moves from theoretical concepts to human testing of these potentially transformative cancer therapeutics.
