Citius Pharmaceuticals and Citius Oncology have announced encouraging preliminary results from an ongoing Phase I clinical trial evaluating the combination of pembrolizumab (KEYTRUDA) and LYMPHIR (denileukin diftitox-cxdl or E7777) in patients with recurrent solid tumors. The investigator-initiated trial, led by Dr. Haider Mahdi at the University of Pittsburgh, aims to determine an optimal dose and assess the impact of the combination on the tumor immune microenvironment.
Promising Early Outcomes
Dr. Mahdi noted the promising results observed in heavily pre-treated recurrent or metastatic gynecologic tumors, with plans to enroll additional patients to complete the Phase I study. The research will further investigate the therapy's impact on Tregs, host immune-effector cells, and the tumor microenvironment in both gynecologic and other solid tumor histologies.
Myron Czuczman, Chief Medical Officer of Citius Pharmaceuticals and Citius Oncology, expressed optimism about LYMPHIR's potential to enhance patient response to pembrolizumab. The proposed mechanism involves temporarily depleting Tregs, which modulate the tumor microenvironment, without inducing autoimmune responses. The positive signals from the data support expanding the research into a Phase II study to evaluate the combination's benefits across a broader range of solid tumor types.
Study Results
The chemotherapy-free regimen combining 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.
- 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 previously received checkpoint inhibitors (i.e., anti-PD-1 therapy), highlighting the 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).
Mechanism of Action and Market Context
Pembrolizumab, a PD-1 inhibitor developed by Merck and marketed as KEYTRUDA, is a leading immunotherapy drug with $25 billion in sales in 2023. It works by blocking the PD-1 protein on T cells, enabling the immune system to recognize and attack cancer cells. LYMPHIR aims to boost pembrolizumab's efficacy by modulating the tumor microenvironment through Treg depletion.
