UCSD Researchers Awarded $18.3M to Study New Combo Therapy for B-cell Cancers

UCSD Researchers Awarded $18.3M to Study New Combo Therapy for B-cell Cancers

The Independent Citizens Oversight Committee of the California Institute for Regenerative Medicine (CIRM) has aproved an $18.29 million grant to researchers at the University of California San Diego (UCSD) School of Medicine to fund a Phase 1b/2a clinical trial that aims to test a new drug combination for B-cell malignancies, such as certain lymphomas and myelomas.

CIRM was created in 2004 with $3 billion to fund stem cell research and treatments in California.

The new trial will study the safety and efficacy of an experimental monoclonal antibody-based drug called cirmtuzumab, and a small molecule drug called Imbruvica (ibrutinib), an inhibitor of the protein Bruton’s tyrosine kinase (BTK), and is approved for chronic lymphocytic leukemia (CLL), mantle cell lymphoma, and Waldenstrom’s macroglobulinemia.

In July, the FDA also approved Imbruvica for patients with chronic graft-versus-host-disease (cGVHD) who failed to respond to other lines of therapy.

Cirmtuzumab, currently in clinical trials for CLL, was designed to target ROR1, a protein on the cell surface present on tumors but not in normal adult tissues, making it an attractive target for anti-cancer therapy.

The investigational drug was developed by Thomas Kipps, an MD and PhD, and his colleagues under a CIRM HALT leukemia grant. Kipps ended up generating antibodies against ROR1, which ultimately led to trials of cirmtuzumab in patients with CLL. The drug’s name was given in honor of CIRM’s longstanding support and funding for research.

“We are very excited about evaluating this combination of targeted therapies in the clinic,” Kipps, who is also the deputy director of research at UCSD Moores Cancer Center, said in a press release. “Although ibrutinib has been approved for treatment of patients with CLL or MCL [mantle cell lymphoma], it is exceptionally rare for this drug by itself to get rid of all the leukemia cells or cause long-lasting remissions without continuous therapy.

“As a result, patients are recommended to take ibrutinib indefinitely – until they develop intolerance or resistance to this drug,” he said. “By blocking a survival/growth-stimulating pathway that provides a lifeline to the leukemia cells of patients taking ibrutinib, cirmtuzumab can work together with ibrutinib to potentially kill all the leukemia cells, allowing patients to achieve a complete remission and stop therapy altogether.”

Cirmtuzumab targets cancer stem cells that behave more like the “roots of the disease,” Kipps said, making stem cell treatments much more effective than traditional therapies, which can eventually allow a cancer to grow back.

By targeting cancer stem cells, “cirmtuzumab may improve our capacity to achieve more complete and longer lasting remissions when used in combination with targeted drugs, such as ibrutinib, or other anti-cancer drugs for the treatment of patients with many different types of cancer,” he added.

Maria Millian, MD, interim president and CEO of CIRM, noted that for people who have run out of treatment options, the only alternative is a bone marrow transplant.

“Since CLL afflicts individuals in their 70s who often have additional medical problems, bone marrow transplantation carries a higher risk of life-threatening complications,” Millian said. “The combination approach of cirmtuzumab and Ibrutinib seeks to offer a less invasive and more effective alternative for these patients.”

Because cirmtuzumab was also shown to be effective against solid tumors, additional trials are planned to test it against the drug Taxol (paclitaxel) for treating metastatic breast cancer. That trial is not yet recruiting participants.

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