AACR 2025 Preview : Rising Momentum for Dual-Payload ADCs

As oncology drug development advances, overcoming tumor heterogeneity and resistance remains a major challenge. One promising approach is the development of dual-payload antibody-drug conjugates (ADCs), which incorporate two distinct therapeutic agents with different mechanisms of action into a single ADC.

According to ApexOnco’s oncology pipeline data, the nascent field of dual-payload ADCs has seen a surge, with 23 new assets entering development over the past six months, representing 40% of all such ADCs ever reported. The surge in interest in this novel class of ADCs is reflected in AACR 2025 abstracts, promising 14 preclinical presentations on dual-payload ADCs[1][2].

Among the posters are two featuring Chengdu Kanghong's TROP2-targeting molecule KH815, which according to a new listing on ClinicalTrials.gov is due to start a phase 1 trial on April 30, making it the first dual-payload ADC to be tested in humans[3].

Table Summarizing Dual-Payload ADCs To Be Presented at AACR 2025

Source: Oncology Pipeline(ApexOnco)

The design of dual-payload ADCs requires careful consideration. It is not merely a matter of attaching two payloads to a monoclonal antibody. Rather, the linker chemistry, payload synergy, and targeted delivery must all be finely tuned to achieve therapeutic efficacy and manageable toxicity.

The rationale behind dual-payload ADCs is to overcome the two major resistance mechanisms observed in ADC-treated patients: loss of the target antigen and resistance to a single payload. Whether this strategy will translate into meaningful clinical benefit remains to be seen—but with the first dual-payload ADC entering clinical trials this month, the field is poised for rapid advancement and potentially transformative impact in oncology.

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Reference：
[1] Oncology Pipeline(ApexOnco)
[2] Beacon
[3] ClinicalTrials.gov

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