Importantly, AB928 synergized with anti-PD-1 therapy to enhance survival in an autochthonous model of metastatic CRC. Our findings define a metabolic immune evasion mechanism in the TME and provide a rationale for targeting neutrophil-derived adenosine signaling to improve immunotherapy responses in CRC and other solid tumors.

P2, N=10, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=20 --> 10

Our findings suggest that inhibition of adenosine activity by blocking the A2B receptor reduces TGFβ signaling and enhances the efficacy of ICI therapy in NSCLC.

P1, N=30, Recruiting, Dwight Owen | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P1, N=36, Not yet recruiting, Adovate

Co-delivery of an ICD inducer (EPI) and an adenosine receptor antagonist (AB928) is realised in a stimuli-responsive nanomedicine to address immunosuppression induced by adenosine, thereby enhancing ICD effects and synergistically reprogramming the immunosuppressive tumor microenvironment.

The reduction of PD-1 expression on CD4⁺ T cells and decreased myeloid-derived suppressor cells were also associated with better outcomes. These findings suggest PBF-1129 is safe and modulates the systemic immune parameters, warranting further evaluation in combination with immune checkpoint blockade.

P2, N=30, Active, not recruiting, Washington University School of Medicine | Trial completion date: Dec 2029 --> Jun 2030 | Trial primary completion date: Oct 2025 --> Apr 2026

Compound 14a also effectively restored T cell proliferation suppressed by 5'-N-ethylcarboxamidoadenosine (NECA) and exhibited superior T cell-mediated cytotoxicity in coculture systems with A1R- and PD-L1-expressed cancer cells compared with ciforadenant (A2AR antagonist) and etrumadenant (A2AR/A2BR dual antagonist). Moreover, the combination of compound 14a with avelumab, an anti-PD-L1 antibody, resulted in enhanced infiltration of effector T cells and significantly increased the CD8+/Treg ratio in the CT26 syngeneic mouse model, substantially inhibiting tumor growth. Therefore, compound 14a is a promising candidate for multitargeted immunomodulation in cancer immunotherapy.

P1/2, N=227, Completed, Arcus Biosciences, Inc. | Active, not recruiting --> Completed | Trial completion date: Mar 2026 --> Sep 2025

P2, N=20, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2025 --> Sep 2027 | Trial primary completion date: Sep 2025 --> Sep 2027

P2, N=43, Recruiting, Weill Medical College of Cornell University | Trial primary completion date: Dec 2025 --> Dec 2026