Development

BioRay moves dual-payload TROP2 ADC into the clinic

BioRay moves dual-payload TROP2 ADC into the clinic

China-based BioRay Pharmaceutical Co., Ltd. has registered a first-in-human Phase I study of BR113, a dual-payload antibody-drug conjugate (ADC) targeting Trop-2, in patients with advanced solid tumors. The trial tests a format that pairs a cytotoxic topoisomerase I inhibitor payload with an immunostimulatory agent on a single antibody scaffold — a design that, if validated clinically, would distinguish BR113 from conventional single-payload ADCs that dominate the current Trop-2 landscape.

The study (NCT07753590) is a multicenter, open-label, single-arm trial enrolling up to 258 adults with unresectable, advanced or metastatic solid tumors that are refractory to or intolerant of standard therapy. The two-stage design progresses from a Phase Ia dose-escalation phase — with dose-limiting toxicity assessment over the first 21 days — to a Phase Ib expansion, with the recommended Phase II dose (RP2D) as the primary endpoint of the latter stage. Secondary endpoints include objective response rate (ORR), progression-free survival (PFS), and pharmacokinetic parameters. The trial is scheduled to begin enrollment in August 2026, with primary completion anticipated in February 2030. Patients with prior exposure to Trop-2-targeted agents, exatecan or exatecan-containing ADCs, or STING pathway agents are excluded.

The Trop-2 ADC field is crowded and increasingly competitive. Gilead Sciences' sacituzumab govitecan (Trodelvy), which delivers SN-38 via a cleavable linker, holds approvals in triple-negative breast cancer and urothelial carcinoma. AstraZeneca and Daiichi Sankyo's datopotamab deruxtecan (Dato-DXd) is advancing through Phase III trials in lung and breast cancers with an exatecan derivative payload.

BR113's proposed differentiation rests on its dual-payload architecture. In a 2025 AACR abstract, BioRay researchers described the ADC as combining a topoisomerase I inhibitor payload with an immunostimulatory payload designed to couple direct tumor-cell killing with activation of antitumor immunity. In vitro experiments showed biological activity from both payloads, while in vivo studies indicated increased immune-cell infiltration and conversion of immunologically "cold" tumors toward a "hot" phenotype. In a syngeneic mouse model, BR113 also provided prolonged protection against tumor rechallenge, which the researchers said was consistent with systemic antitumor immunity. Combining BR113 with checkpoint inhibition further increased antitumor activity in an aggressive B16F10 model.

The specific identities of both payloads remain undisclosed. Exclusion of patients previously treated with exatecan or exatecan-containing ADCs and STING pathway agents in the Phase I study provides clues to their possible identities, but BioRay has not publicly confirmed either payload.

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BioRay has separately developed BR111, an anti-ROR1 biparatopic ADC using its proprietary CysX site-specific conjugation platform, which received China National Medical Products Administration (NMPA) clinical trial approval in December 2024. Whether BR113 uses the same CysX platform or a distinct conjugation technology has not been publicly stated. No licensing, partnership, or financing deals specific to BR113 have been disclosed.

The primary completion date of February 2030 sets the earliest window for interpretable efficacy data from the Phase Ib expansion cohort, at which point BioRay would need to decide whether to advance into indication-specific Phase II trials or seek a development or commercialization partner.


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