Citius Pharmaceuticals Announces Clinical Collaboration with the University of Pittsburgh

Citius Pharmaceuticals, a late-state biopharmaceutical company, recently announced a collaboration with Haider Madhi, MD, an assistant professor at the University of Pittsburgh. The collaboration will focus on an investigator-initiated trial evaluating I/ONTAK (denileukin diftitox), a recombinant fusion protein that combines the interleukin-2 (IL-2) receptor binding domain with diphtheria toxin fragments, in combination with pembrolizumab, for the treatment of recurrent or metastatic solid tumors.

According to a company press release, the trial is an open label, Phase I/Ib study designed to evaluate regulatory T-cell (T-regs) cell depletion through the denileukin diftitox and pembrolizumab combination; it consists of two parts. Part I is a dose escalation study of four cohorts (3, 6, 9, 12 mcg of denileukin diftitox) that is expected to enroll 18–30 patients. Part II is a dose expansion study enrolling approximately 40 patients to evaluate the safety and tolerability of the recommended dose. Additionally, the study will investigate the alteration of the immune microenvironment within tumors and peripheral blood.

"This study will expand the body of knowledge about [denileukin diftitox] unique mechanism-of-action targeting the CD25 component of the IL2-receptor, which is present on both malignant T-cells (T-cell leukemias and lymphomas) and immunosuppressive T-regs," said Myron Czuczman, chief medical officer, Citius Pharmaceuticals, in the release. "Preclinical research in a syngeneic solid tumor mouse model shows that [denileukin diftitox] enhances anti-tumor activity and significantly extends [the] survival benefit of anti-PD-1 [programmed cell death 1] therapy. This data provides a positive signal of denileukin diftitox's potential in the immuno-oncology space.”

"Encouraging clinical data emerging in the field of tumor immunotherapy have demonstrated that therapies focused on enhancing T-cell responses against cancer result in a significant survival benefit in patients with advanced malignancies,” said Mahdi in the release. “Overexpression of PD-L1 [programmed cell death ligand 1] on tumor cells has been reported to impede anti-tumor immunity, resulting in immune evasion. The interruption of the PD-1:PD-L1 pathway combined with diminishing the suppressive effect by T-regs may represent an attractive strategy for restoring tumor-specific T-cell immunity.”

In addition to this study withUniversity of Pittsburgh, Citius is collaborating with an investigator-initiated study at the University of Minnesota. This Phase I dose-finding study is to evaluate denileukin diftitox prior to tisagenlecleucel chimeric antigen receptor-T cell therapy in patients with diffuse large B-cell lymphoma; the study enrolled its first patient in May 2021.

Source: Citius Pharmaceuticals