Two CIRM-funded research projects receive RMAT designation from FDA

The U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to two research projects funded by the California Institute for Regenerative Medicine (CIRM).

RMAT is a fast-track designation that can help speed up the development, review, and potential approval of treatments for serious or life-threatening diseases.

The first RMAT designation was awarded to a GD2-CAR T cell therapy being studied in a Stanford Medicine clinical trial led by Crystal Mackall, MD, Founding Director of the Stanford Medicine Center for Cancer Cell Therapy and Co-leader of the Stanford Cancer Institute Cancer Immunotherapy Program, and Michelle Monje, MD, PhD, the Milan Gambhir Professor in Pediatric Neuro-Oncology and professor of neurology at Stanford Medicine.

CIRM provided $12 million in funding to support the Stanford Medicine clinical trial and has provided early-stage research funding to Dr. Monje to better understand the role of glial cells in the childhood brain. CIRM has also previously supported Dr. Mackall's research through an $11 million grant exploring the use of CAR-T cells to treat B cell malignancies.

The second RMAT designation was granted to Allogene Therapeutics for the treatment of adult patients with CD70 positive advanced or metastatic renal cell carcinoma (RCC), the most common type of kidney cancer worldwide. CIRM awarded $15 million to John Le Gall, MD, and his team at Allogene Therapeutics to advance ALLO-316.

A CAR T cell treatment for deadly brain and spinal cord tumors

In the Stanford Medicine clinical trial, CAR-T cells showed promise against pediatric diffuse midline gliomas, a type of brain and spinal cord tumor that are among the deadliest cancers. Until now, radiation therapy has been the standard treatment, but its impact is limited, offering only a few additional months of survival.

Mackall, Monje, and their teams developed a unique approach to treating these types of brain cancers. They modified a patient's own T cells (immune system cells) with a protein called chimeric antigen receptor cell (CAR). These newly created CAR-T cells were then reintroduced back into the patient's body where they helped to identify and destroy the brain tumor cells.

So far, the immune-cell therapy has shown positive results, in many cases shrinking children's brain tumors and restoring neurologic function. In one trial participant, all detectable traces of a brain cancer were erased and he is healthy more than four years after his diagnosis.

The findings were recently published in Nature.

"The RMAT designation is great news for the team at Stanford Medicine and for the children and families affected by gliomas and devastating cancers," says Jonathan Thomas, PhD, JD, President and CEO of CIRM. "The designation means that innovative, life-saving therapies like this may be able to advance more rapidly to full approval by the FDA and be available to patients who need them."

In addition to CIRM's funding support of the project, the research also received funding from the Parker Institute for Cancer Immunotherapy, CureSearch, the National Cancer Institute, St. Baldrick's Foundation to the Empowering Pediatric Immunotherapy Immunotherapies for Pediatric Cancer Team, Alex's Lemonade Stand Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, ChadTough Defeat DIPG Foundation, and Oscar's Kids Foundation.

A new therapeutic approach to treating kidney cancer

The RMAT designation for Allogene's ALLO-316, an allogeneic CAR-T cell therapy, represents another step forward in the development of therapies to treat kidney cancer.

Metastatic renal cell carcinoma (RCC) presents significant challenges with limited treatment options, especially for patients whose cancer has progressed following treatment with checkpoint blockers and targeted therapies. The five-year survival rate for advanced kidney cancer is less than 17 percent, highlighting the urgent need for new therapeutic approaches.

Allogene's ALLO-316 CAR-T cell therapy targets CD70, a protein highly expressed on clear cell renal cell carcinoma (ccRCC) tumors. By focusing on CD70-positive cancer cells, this therapy offers a promising new approach to treating kidney cancer.

Initial data from the CIRM-funded Phase 1 TRAVERSE trial, presented at the American Association for Cancer Research (AACR) 2023 and The Society for Immunotherapy of Cancer's 2024 (SITC) Annual Meetings, showed encouraging response rates and early anti-tumor activity, suggesting deepening responses over time.

"CAR-T has revolutionized the treatment of hematologic malignancies, and we believe CIRM's support and the RMAT designation validates the remarkable progress we have made in our TRAVERSE trial," said Zachary Roberts, MD, PhD, Executive Vice President of Research & Development and Chief Medical Officer of Allogene.

"ALLO-316 has shown significant promise for patients with advanced RCC who have exhausted standard therapies. We are grateful for the support from CIRM and look forward to advancing this trial."

To learn more about Stanford Medicine's RMAT designation and clinical trial, visit this page. To learn more about Allogene's RMAT designation and clinical trial, visit this page.