An ongoing Phase I clinical trial evaluating the combination of pembrolizumab (KEYTRUDA) and LYMPHIR (denileukin diftitox-cxdl or E7777) has shown promising preliminary results 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 combined regimen on the tumor immune microenvironment.
Promising Results in Heavily Pre-treated Patients
Dr. Mahdi noted the encouraging results observed in patients with heavily pre-treated recurrent or metastatic gynecologic tumors. The trial plans to enroll three additional patients to complete the Phase I portion, with further investigation planned for gynecologic and other solid tumor histologies to explore the therapy's impact on Tregs, host immune-effector cells, and the tumor microenvironment.
Potential to Enhance Pembrolizumab Response
Dr. Myron Czuczman, Chief Medical Officer of Citius Pharmaceuticals and Citius Oncology, expressed optimism about LYMPHIR's potential to enhance patient response to pembrolizumab. The hypothesis is that LYMPHIR temporarily depletes Tregs, which modulate the tumor microenvironment, without triggering an autoimmune response. The positive signals from the data support expanding the research into a Phase II study to further evaluate the combination's benefits across a broader range of solid tumor types.
Study Results: ORR and PFS
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. The median progression-free survival (PFS) for patients achieving clinical benefit was 57 weeks, ranging from 30 to 96 weeks. Notably, two of the four patients who achieved partial remission had previously received checkpoint inhibitors, highlighting the potential of LYMPHIR plus immune checkpoint inhibitors to be effective in patients who fail prior anti-PD-1/L1 therapy.
Trial Details and Tolerability
The trial enrolled 21 patients with recurrent or metastatic solid tumors. Among the evaluable participants, four achieved a partial response, and one 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).
