A new Phase 3 trial for advanced melanoma patients who failed to respond to Opdivo (nivolumab) or Keytruda (pembrolizumab) is recruiting participants to evaluate Idera Pharmaceutical‘s experimental immunotherapy, IMO-2125, in combination with Yervoy (ipilimumab).
The study, called ILLUMINATE 301 (NCT03445533), will determine if the combination is better at extending survival than Yervoy alone. Another primary goal is to determine the proportion of patients responding to the treatment.
“We are excited to initiate the ILLUMINATE 301 trial, grateful to our advisers who have worked with us to design this pivotal trial and very encouraged by the enthusiasm of investigators to participate in the study,” Joanna Horobin, Idera’s chief medical officer, said in a press release. ”
“We look forward to working together to conduct and complete this trial, so that we may bring IMO-2125 to the market as soon as possible for patients who are not benefiting from anti-PD-1 therapy,” she added.
The trial is expected to enroll 308 patients with advanced melanoma, whose disease progressed while on anti-PD-1 therapy (Opdivo or Keytruda). Patients are being recruited in the United States — currently at the Greater Baltimore Medical Center, Maryland — but Idera will expand its recruitment efforts to other U.S. and international sites for a total of 80 centers.
Participants will be randomly assigned IMO-2125 plus Yervoy or Yervoy alone. IMO-2125 will be delivered directly into the tumor in nine doses. Yervoy will be administered intravenously in four doses.
Preclinical and Phase 1/2 trial data have shown that the combination of IMO-2125 and Yervoy is well-tolerated and actively promotes anti-tumor immune responses. The treatment induced responses even in distant tumors that did not receive IMO-2125 treatment.
This happens when immune cells from the treated tumor are primed to recognize the cancer cells and travel through the body to eliminate signs of cancer in distant locations.
The Phase 3 trial is now expected to provide definite evidence that IMO-2125 plus Yervoy is better than Yervoy alone in this patient population.
IMO-2125 works by activating a protein called toll-like receptor (TLR9), found at the surface of immune cells — dendritic and B-cells. Once activated by the treatment, these cells will go on to activate cancer-fighting T-cells.
The experimental drug received fast track status from the U.S. Food and Drug Administration in November 2017. The designation ensures expedited development and review of medicines for serious or life-threatening disease, such as refractory metastatic melanoma.
“For our advanced melanoma patients who have not benefited from anti-PD-1 therapy and in BRAF mutant melanoma, BRAF targeted therapy, there are very few, limited options available today,” said Ahmad Tarhini, MD, director of the Melanoma and Skin Cancer Program at Cleveland Clinic Taussig Cancer Institute.
“I am encouraged by the data that has been demonstrated to date with IMO-2125 and am hopeful that this Phase 3 trial offers hope to this large group of patients whose treatment options are very limited,” he said.