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

Single-cell analysis revealed distinct functional subpopulations of macrophages and T cells, highlighting the complexity of immune heterogeneity and the potential for targeting specific immune cell subpopulations to enhance therapeutic efficacy. These findings suggest that the combination therapy of PARPi and A2ARa is a highly promising strategy that overcomes PARPi-induced immune escape by targeting the cAMP/CREB axis, thereby synergistically enhancing antitumor effects and holding promise as an effective treatment for solid tumors.

Correspondingly, their motor activity also improved. These results suggest that AAVrh10-based intrathecal delivery combined with istradefylline provides a promising therapeutic strategy for treating Tay-Sachs disease.

P1/2, N=40, Active, not recruiting, University of Florida | Recruiting --> Active, not recruiting | Trial completion date: May 2026 --> Aug 2026

P1, N=60, Recruiting, Chong Kun Dang Pharmaceutical | Not yet recruiting --> Recruiting

P1, N=40, Recruiting, Janssen Research & Development, LLC

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.

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

However, unlike blinatumomab, which tends to induce T cell exhaustion, we showed that the release of PBF-509 from NanoBiTE suppressed the A2AR pathway and substantially improved tumor cell killing induced by NanoBiTE. Moreover, NanoBiTE treatment led to substantially reduced tumor burden in vivo in a humanized mouse model. Our results demonstrate that NanoBiTE is a safe and potent bispecific therapy that can also reduce T cell exhaustion for cancer immunotherapy.

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

P1, N=60, Not yet recruiting, Chong Kun Dang Pharmaceutical