Copiktra (duvelisib)

We present the case of a 61-year-old man with CD8+ AECTCL who developed a methicillin-sensitive Staphylococcus aureus port-site infection while on duvelisib following prior gemcitabine/liposomal doxorubicin therapy...Complement studies supported the activation of the alternative pathway, and after multidisciplinary discussion, eculizumab was initiated for TMA management...His cutaneous lymphoma lesions improved with a short course of oral prednisone as directed by oncology. At discharge, he was clinically stable on dialysis with plans for ongoing outpatient care; subsequent follow-up showed stable renal function. This case highlights the intersection between aggressive cutaneous lymphoma, infection, and chemotherapy-induced vascular injury, emphasizing the importance of early recognition of systemic complications in CD8+ AECTCL and the need for a multidisciplinary approach to optimize patient outcomes.

The DUV-NCs were found to be safe in toxicity studies with no major alterations in biomarkers compared to the control. In conclusion, DUV-NCs is a promising strategy to deliver DUV in hematological malignancies with improved efficacy and safety.

P2, N=15, Active, not recruiting, City of Hope Medical Center | Trial completion date: Nov 2025 --> Oct 2026

P2, N=17, Active, not recruiting, Washington University School of Medicine | Trial completion date: Dec 2025 --> Apr 2026 | Trial primary completion date: Dec 2025 --> Apr 2026

P1, N=38, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2027 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=25, Not yet recruiting, City of Hope Medical Center

P1/2, N=13, Terminated, John Kirkwood | Trial completion date: Dec 2028 --> Feb 2025 | Active, not recruiting --> Terminated; Secura Bio, Inc. discontinued support of the trial.

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

This study examined the effects of signaling pathway inhibitors ibrutinib, idelalisib, duvelisib, and venetoclax on the expression of immune checkpoint ligands: Programmed death ligand 1 (PD-L1), galectin-9 (Gal-9), cluster of differentiation (CD)200, CD155, and herpes virus entry mediator (HVEM) in CLL leukemic cells. Altogether, the treatment of leukemic cells with different SMIs in this study indicated increased or decreased variations in the expression level of immune checkpoint inhibitory ligands in CLL. Therefore, these mechanisms should be considered for further treatment approaches, especially for combinational strategies.

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