By Fineline Cube 
China-based Chengdu Kanghong Pharmaceutical Group Co., Ltd. (SHE: 002773) has received clinical trial approval from China’s National Medical Products Administration (NMPA) for its investigational drug KH815, a dual-payload antibody-drug conjugate (ADC) targeting trophoblast cell-surface antigen 2 (TROP-2). This milestone marks a significant advancement in the development of innovative therapies for advanced solid tumors.
Mechanism and Innovation
KH815 is an in-house-developed ADC designed to simultaneously suppress tumorigenic pathways at both RNA and DNA levels through a dual-mechanism synergistic action. Preclinical data indicate that KH815 downregulates P-glycoprotein (P-gp) and heat shock protein 70 (HSP70), effectively counteracting drug resistance mechanisms and enhancing tumor cell sensitivity to conventional chemotherapy.
Preclinical Efficacy
In vitro studies demonstrated KH815’s nanomolar-range cytotoxic activity against tumor cells with varying TROP-2 expression profiles. In vivo evaluations using cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models showed dose-proportional tumor growth inhibition across multiple cancer types. Notably, KH815 maintained efficacy in models resistant to camptothecin-based ADCs, suggesting potential for overcoming clinical resistance.
Clinical Advantages
The dual-payload architecture of KH815 offers two key clinical advantages: higher tumor response rates compared to single-payload ADCs and activity against resistance mechanisms in patients refractory to camptothecin-based monotherapy ADCs. These features position KH815 as a promising candidate for addressing unmet medical needs in advanced solid tumors.-Fineline Info & Tech