Citius Pharmaceuticals Inc. and Citius Oncology Inc. have announced promising preliminary results from an ongoing investigator-initiated Phase I clinical trial evaluating the safety and efficacy of a combined regimen of pembrolizumab (KEYTRUDA) and LYMPHIR (denileukin diftitox-cxdl or E7777) in patients with recurrent solid tumors.
 
The trial is being conducted by Haider Mahdi, M.D., Assistant Professor, Department of Obstetrics, Gynecology & Reproductive Sciences, at the University of Pittsburgh. It aims to identify an optimal dose for future trials and explore the impact of a treatment regimen combining pembrolizumab and LYMPHIR on the tumor immune microenvironment.
 
“We have seen promising results in patients with heavily pre-treated recurrent or metastatic gynecologic tumors and will enroll three additional patients before completing the Phase I portion of this study,” said Mahdi. “We will further investigate in patients with gynecologic tumors and those with other solid tumor histologies. We want to explore the impact of this therapy on Tregs, host immune-effector cells and the tumor microenvironment.”
 
“There is reason to be optimistic about the potential of LYMPHIR to boost a patient’s response to pembrolizumab by temporarily depleting Tregs that modulate the tumor microenvironment, without triggering an autoimmune response from the patient’s body. We believe the positive signals from this data support expanding the research in a Phase II study to further evaluate the combination’s benefits across a broader range of solid tumor types,” added Dr. Myron Czuczman, Chief Medical Officer of Citius Pharmaceuticals and Citius Oncology.
 
PD-1 inhibitors such as pembrolizumab are a type of immune checkpoint inhibitor that works by blocking the PD-1 protein on T cells, enabling the immune system to recognize and attack cancer cells. Pembrolizumab, developed by Merck and sold under the brand name KEYTRUDA, is the leading PD-1 inhibitor and world’s most prescribed drug, generating $25 billion in sales in 2023.

Results of the Study

The results of this chemotherapy-free regimen combining two immuno-modulator agents, pembrolizumab (anti-PD-1) and LYMPHIR (transient Treg depletion) demonstrated:
 

• An overall response rate (ORR) of 27% (4/15) and a clinical benefit rate of 33% (5/15) among evaluable patients; and,
• Median progression-free survival (PFS) for patients achieving clinical benefit of 57 weeks, with a range of 30 to 96 weeks.
• Notably, two of the four patients who achieved partial remission had received prior checkpoint inhibitors (i.e. anti-PD-1 therapy). This highlights the therapeutic potential of LYMPHIR plus immune checkpoint inhibitors to be effective in patients who fail prior anti-PD-1/L1 therapy.

 
The trial enrolled 21 patients with recurrent or metastatic solid tumors. Among the evaluable participants, four patients achieved a partial response, and one patient demonstrated durable stable disease lasting over six months. The combination regimen was generally well tolerated, with most adverse events related to the patients’ underlying disease. Importantly, no significant immune-related adverse events were observed, and only one case of dose-limiting toxicity (capillary leak syndrome) was reported at the highest dose level (12 mcg/kg).