Stand Up To Cancer’s ‘Dream Team’ to Investigate Devimistat Combo Therapy for T-cell Lymphoma

Stand Up To Cancer’s ‘Dream Team’ to Investigate Devimistat Combo Therapy for T-cell Lymphoma

Rafael Pharmaceuticals‘ devimistat (CPI-613) — which targets the metabolic alterations in cancer cells — will be studied as part of a combination therapy for the treatment of T-cell lymphoma, the company announced.

The project, “Tailoring CAR-based immunotherapy strategies to T-Cell Lymphoma,” is part of Stand Up To Cancer’s Dream Team Research Grant, meant to develop new therapies for T-cell lymphoma.

“We must develop better treatments for those with T-cell lymphomas. Although treatments are available, many patients who achieve remission will, unfortunately, experience a relapse. In addition, there is no consensus treatment for patients with this recurrent and difficult to treat disease,” Zanetta Lamar, MD, a lymphoma specialist and an investigator in the project, said in a press release.

Stand Up To Cancer, based in Los Angeles, recently set up a “dream team” of expert scientists to develop new immunotherapies for T-cell lymphoma based on CAR T-cell immunotherapy.

The team’s main goal is to develop donor-derived CAR T-cells that will be available on an “off-the-shelf” basis.

CAR T-cell therapy — which consists of collecting a patient’s own T-cells and modifying them in the lab to recognize cancer cells more effectively — is usually personalized; a donor-derived treatment could improve availability and reduce costs.

In addition, the team will test the devimistat combination as a means of preparing patients for receiving the CAR T-cell therapy, while reducing the amount of chemotherapy used in this setting. They believe that this combination represents a unique way to treat cancer without the side effects, such as hair loss, of standard chemotherapies.

Researchers will also use genetic tests to identify patients more likely to respond to devimistat.

“Our motto, ‘To Save A Life Is To Save A Universe,’ illustrates our desire to develop potential treatments for patients with significant unmet clinical need,” said Sanjeev Luther, president and CEO of Rafael Pharmaceuticals. “Research under this grant will explore devimistat in a new combination for T-Cell Lymphoma, and we believe this will help in identifying new therapeutic options.”

Devimistat targets a part of the metabolism used by cancer cells to survive and proliferate — the mitochondrial tricarboxylic acid cycle — preventing them from being able to produce energy at the rate they need to proliferate.

The therapy is also known to increase the sensitivity of the tumor cells to other chemotherapeutic agents, widening its scope to target multiple forms of cancers.

In a Phase 1 clinical trial (NCT02168140) in T-cell lymphoma patients who had exhausted all available treatments, a combination of devimistat and bendamustine hydrochloride led to 43% of patients being cancer-free and reduced tumor volume in an additional 43%.

Bendamustine hydrochloride, marketed as Bendeka in the U.S., is a chemotherapeutic agent developed by Cephalon, a subsidiary of Teva Pharmaceuticals. Devimistat also increased the sensitivity to chemotherapeutic agents in acute myeloid leukemia and pancreatic cancer.

Devimistat has received five orphan drug designations by the U.S. Food and Drug Administration for peripheral T-cell lymphoma, Burkitt’s lymphoma, pancreatic cancer, acute myeloid leukemia, and myelodysplastic syndromes.

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