Combining OncoSec Medical‘s intratumoral therapy, ImmunoPulse IL-12, with an immune checkpoint inhibitor is a promising approach for triple-negative breast cancer patients, a Phase 1 clinical trial suggests.
The approach induced robust objective responses in two patients with metastatic triple-negative breast cancer who had already had received multiple lines of therapy. Such patients typically do not respond to checkpoint inhibitors.
“Metastatic TNBC is a heterogeneous cancer with a poor prognosis where less than five percent of pre-treated patients achieve an objective response to PD-1/PD-L1 checkpoint treatments,” Sharron Gargosky, chief clinical and regulatory officer of OncoSec, said in a press release.
This happens because triple-negative breast cancers are typically devoid of tumor-infiltrating T-cells, which are needed for checkpoint inhibitors to work. These medicines activate T-cells, but do not recruit them into tumors. Therefore, approaches that recruit and expand T-cells within tumors are thought to enhance the response to immune checkpoint inhibitors.
ImmunoPulse IL-12 consists in the intratumoral injection of a DNA strand coding for the interleukin-12 (IL-12) protein, followed immediately by electroporation. Electroporation is a technique that opens small pores in the cells’ membranes, allowing the DNA molecule to enter.
The approach leads to a localized expression of IL-12 in the tumor microenvironment, which has been shown to increase the expansion of cytotoxic tumor-infiltrating T-cells.
The pilot clinical trial (NCT02531425) of ImmunoPulse IL-12 in metastatic triple-negative breast cancer was designed to assess if a single injection increased tumor immunogenicity, or the amount of T-cells in the tumor site.
To date, five patients have received the treatment, two of which received Opdivo (nivolumab), an anti-PD-1 checkpoint inhibitor, as their immediate next therapy.
While these patients had received several courses of therapy, both experienced encouraging responses. Importantly, tumor reductions were seen in both ImmunoPulse IL-12 treated and untreated lesions.
“The marked synergy shown in these patients strongly suggests that IL-12 may have primed the tumor microenvironment, impacting the clinical result. The combination of ImmunoPulse IL-12 and checkpoint inhibition represents a highly promising new therapeutic approach for TNBC and warrants a formal evaluation given the extremely low response rate in women who have failed multiple prior therapies,” Gargosky said.
Based on the findings, the company plans to initiate a more definitive evaluation of the combination treatment.
These data, along with the full information regarding final observations and safety data, will be submitted for presentation at an upcoming medical conference.