Intratumoral Therapy Increases Response to Checkpoint Inhibitor in Triple Negative Breast Cancer, Study Finds

Intratumoral Therapy Increases Response to Checkpoint Inhibitor in Triple Negative Breast Cancer, Study Finds

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.

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