AK158D1, a bispecific antibody-drug conjugate (ADC) simultaneously targeting epidermal growth factor receptor (EGFR) and trophoblast cell surface antigen 2 (TROP2), has received Phase I clinical trial clearance from China's National Medical Products Administration (NMPA), allowing China-based Akeso (HKEX: 9926.HK) to begin first-in-human testing in patients with advanced malignant solid tumors.
AK158D1 pairs a humanized bispecific antibody with a cytotoxic payload designed to engage both EGFR and TROP2 simultaneously. Akeso said preclinical studies demonstrated strong antigen-binding affinity alongside robust in vitro and in vivo anti-tumor activity with a favorable safety profile. The company contends that dual targeting addresses three limitations it associates with single-target ADCs directed at either antigen alone: narrow tumor coverage, off-target toxicity, and multidrug resistance.
AK158D1 is Akeso's fourth ADC to enter clinical development and its second bispecific ADC to reach the clinic. The three others — AK146D1 (TROP2/Nectin-4), AK138D1 (HER3), and AK157D1 (B7-H3) — have each progressed to dosing within the past several months, with AK138D1 and AK146D1 already in Phase Ib/II and Phase II studies respectively, both in combination with ivonescimab, Akeso's approved PD-1/VEGF bispecific antibody.
AK158D1 enters an emerging but still early competitive field of EGFR/TROP2 bispecific ADCs. Xadcera/Doma’s DM001 has already advanced into clinical testing in advanced solid tumors, while DXC024 has been disclosed preclinically. The approach is intended to exploit co-expression of EGFR and TROP2 to improve tumor selectivity and activity relative to single-target ADCs.