Combining Idera Pharmaceuticals‘ intratumoral IMO-2125 treatment with Yervoy (ipilimumab) may be a promising treatment approach for patients with metastatic melanoma who are refractory to anti-PD-1 therapies, according to preliminary data from a Phase 1/2 clinical trial.
“We are very pleased with the progress to date in the Phase 1 dose escalation trial of IMO-2125 in combination with ipilimumab, and with the outcomes observed,” Joanna Horobin, Idera’s chief medical officer, said in a press release.
“IMO-2125 in combination with ipilimumab demonstrated preliminary evidence of meaningful clinical activity in this anti-PD-1 refractory metastatic melanoma patient population which represents a high unmet medical need,” she said.
“All dose levels have been well tolerated and did not exacerbate the safety issues commonly observed with ipilimumab,” Horobin said. “Furthermore, data from multiple parameters of immune markers from tumor biopsies have been very informative in establishing proof-of-mechanism and supporting the dose selection for the Phase 2 portion of the trial.”
IMO-2125, a toll-like receptor (TLR) agonist, is designed to activate cells from the innate immune system and induce the production of interferon — a potent activator of the immune system. Together, this is thought to lead to the infiltration of tumor-killing T-cells.
Because tumors have developed a method to impair T-cells from recognizing and attacking them, Idera believes that the drug could work in synergy with known and approved immune checkpoint inhibitors.
The open-label Phase 1/2 study (NCT02644967) was designed to assess the safety and preliminary effectiveness of intratumoral IMO-2125 in combination with the CTLA-4 inhibitor Yervoy or the PD-1 inhibitor Keytruda (pembrolizumab) in patients with metastatic melanoma who progressed after receiving anti-PD-1 therapies.
The study was set to be conducted in two parts: a dose-escalation portion (Phase 1) to evaluate safety and tolerability of multiple dose levels, and a Phase 2 expansion portion to assess efficacy.
While the Phase 1 dose escalation of IMO-2125 in combination with Keytruda is ongoing, the company has now announced that the Phase 1 part assessing IMO-2125 plus Yervoy has met the pre-specified futility assessment, meaning that the combination reached the established efficacy cut-off.
The company announced that all dose levels of IMO-2125 were well tolerated, and that the 8 mg dose level was established as the recommended Phase 2 dose.
Nine participants out of an expected 21 have enrolled in the Phase 2 portion of the trial assessing the objective response rate of IMO-2125 in combination with Yervoy. Data will be compared with historical controls treated with Yervoy alone.
Houston’s MD Anderson Cancer Center will continue to lead the study and will be joined by other clinical sites. Idera expects to have overall response rate (ORR) data early next year.
“I am very encouraged by the tremendous progress that has been made to date to advance us to this important stage in IMO-2125’s development cycle,” said Vincent Milano, Idera’s CEO. “There is a very clear unmet medical need for those patients for whom current checkpoint inhibitor therapies are not providing adequate solutions.
“We are incredibly focused on advancing this program as rapidly as possible for these patients, and we are also looking forward to exploring areas outside of melanoma in which intratumoral IMO-2125 may also serve an important role through its unique mechanism of action within the tumor microenvironment,” he said.
Idera also said it has started meeting with regulatory agencies about the best path to follow to register the combined treatment of IMO-2125 and Yervoy in patients with PD-1 refractory metastatic melanoma.
In addition, the company said the Phase 1 clinical trial evaluating the combined treatment of intratumoral IMO-2125 and Keytruda in PD-1 patients with refractory melanoma is enrolling as planned.
Moreover, a Phase 1 clinical trial evaluating intratumoral IMO-2125 alone (NCT03052205) in multiple tumor types should be enrolling the first patient in coming months.