A first-in-human (FIH) clinical trial of FXB0871 (TEV-56278), an anti-PD-1/IL-2 antibody-cytokine fusion protein, has been registered in China, with HKEX- and SSE-listed Fosun Pharma serving as the regional developer under an exclusive license from Israel-based Teva Pharmaceutical Industries. The Phase Ia/Ib study targets adults with locally advanced or metastatic solid tumors, with a specific focus in the expansion phase on patients whose disease has progressed on or become resistant to PD-(L)1 checkpoint inhibitors — a population for whom few mechanistically distinct options currently exist.
The open-label, multicenter trial (NCT07558200) will enroll approximately 138 participants across two sequential parts. Part Ia is a dose-escalation phase enrolling adults with selected solid tumors that have progressed on, are intolerant to, or are otherwise unsuitable for standard therapy; it uses a Bayesian optimal interval design to determine the maximum tolerated dose and recommended Phase 2 dose (RP2D). Part Ib is a dose-expansion phase restricted to patients with PD-(L)1-resistant non-small cell lung cancer (NSCLC) or hepatocellular carcinoma (HCC), with NSCLC participants randomized 1:1 between the RP2D and a lower dose selected from Part Ia data. FXB0871 is administered by intravenous infusion every two weeks, with schedule optimization to every three or four weeks permitted based on pharmacokinetic, pharmacodynamic, and safety data. Treatment may continue for up to 12 months. The trial is set to begin enrolling in May 2026, with primary completion anticipated in April 2030. Participants must have ECOG performance status 0 or 1 and at least one measurable lesion per RECIST v1.1. The primary endpoints are the incidence and severity of adverse events and dose-limiting toxicities in Part Ia, and objective response rate in Part Ib; secondary endpoints include pharmacokinetic parameters, duration of response, progression-free survival, and overall survival.
FXB0871 belongs to a class of molecules designed to address a long-standing tension in cytokine-based immunotherapy: IL-2 has potent T-cell stimulatory activity but, at systemic doses, produces severe toxicity including vascular leak syndrome, which has constrained its clinical use for decades. The molecule pairs a non-blocking anti-PD-1 antibody — one that binds PD-1 at an epitope distinct from the PD-L1 binding site, thereby preserving checkpoint receptor function — with a highly attenuated IL-2 variant. The intent is to deliver the IL-2 payload selectively to PD-1-expressing tumor-infiltrating T cells, where it can drive CD8+ effector T-cell proliferation and activation within the tumor microenvironment while limiting systemic cytokine exposure. Preclinical data presented at ASCO 2025 indicated preferential engagement of effector CD8+ T cells over regulatory T cells, which is mechanistically relevant given that unmodified IL-2 expands Tregs via the high-affinity IL-2Rα (CD25) receptor, potentially counteracting anti-tumor immunity. The Teva–Fosun partnership announcement from June 2025 describes the molecule as a product of Teva's internally developed ATTENUKINE platform.