In the syngeneic CT26 model, dual PI3Kδ/γ inhibition (BR101801 or duvelisib), unlike selective PI3Kδ inhibition (idelalisib), synergized with RT (7.5 Gy) to suppress tumor growth and induce durable immune memory. Furthermore, blockade of the IFN-I receptor abolished CD8+ T cell infiltration and M2-like macrophage suppression, abrogating antitumor efficacy and confirming the requirement for IFN-I signaling. These findings identify macrophage-driven activation of the cGAS-STING-IFN-I axis as a key mechanism by which dual PI3Kδ/γ inhibition potentiates RT, providing a strong scientific rationale for its development as an immunomodulatory radiosensitizer.

P2, N=40, Recruiting, Rhizen Pharmaceuticals SA | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Oct 2025 --> Dec 2026

P2, N=26, Completed, Glenn J. Hanna | Active, not recruiting --> Completed

In this study, we systematically validated the synergistic therapeutic potential of HDAC inhibitor chidamide and PI3K inhibitor duvelisib in p53+ DLBCL through cellular models, in vivo experiments, and clinical samples. This acetylation promoted histone H1.5-IκBα interactions, further stabilizing IκBα and attenuating p65 nuclear trafficking. Our findings identify a novel and potent therapeutic strategy for p53+ DLBCL, warranting clinical translation.

P2, N=44, Not yet recruiting, Boryung Pharmaceutical Co., Ltd

P2, N=170, Suspended, Alliance for Clinical Trials in Oncology | Recruiting --> Suspended

P1, N=26, Completed, Boryung Pharmaceutical Co., Ltd | Active, not recruiting --> Completed

UTMD mediated delivery using IPI549@αIMBs combined with anti-PD1 therapy markedly inhibited subcutaneous ATC tumor growth in mice, effectively reduced the proportion of M2-like tumor associated macrophage, and increased CD8+ T cell infiltration, which alleviated the tumor immunosuppressive state. In summary, this study explored a novel therapeutic strategy for ATC, demonstrating the efficacy of the IPI549@αIMB-based UTMD approach combined with anti-PD1 therapy and validating the underlying immunomodulatory mechanisms.

P1/2, N=32, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jul 2025 --> Jul 2026

P1, N=30, Recruiting, Memorial Sloan Kettering Cancer Center | Not yet recruiting --> Recruiting

P1, N=56, Completed, Kither Biotech Srl | Recruiting --> Completed

P2, N=15, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jun 2025 --> Nov 2025