City of Hope presents research at American Society of Hematology conference on mosunetuzumab plus polatuzumab vedotin for patients with relapsed or refractory large B cell lymphoma

The research also published simultaneously in Nature Medicine

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Letisia Marquez
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LOS ANGELES -- New therapies for patients with relapsed or drug-resistant large B cell lymphoma remain an area of unmet need. A Phase 1b/2 study examined the effects of gradually increasing doses of mosunetuzumab in combination with polatuzumab vedotin (pola) on aggressive lymphomas that did not respond to prior treatment.

City of Hope's Elizabeth Budde, M.D., Ph.D., published research in Nature Medicine.

Elizabeth Budde, M.D., Ph.D., City of Hope associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, and executive medical director of the Enterprise Immune Effector Cell Program, reported the primary results from the phase 2 portion in an oral abstract at ASH conference, which simultaneously published in Nature Medicine.

Mosunetuzumab is a bispecific antibody that engages and redirects T cells to eliminate malignant B cells. One arm targets the CD3 protein on T cells, an immune cell that fights against cancer once activated, and a second arm binds to CD20, a protein commonly found on lymphoma cells.

"The two cell groups are pulled together, with mosunetuzumab serving as a kind of bridge," Budde said. "The close proximity triggers the activated T cells to recognize and attack the lymphoma cells, while polatuzamab vedotin finds and kills dividing B cells."

A group of 120 patients, who ranged in age from 20 to 88, were enrolled in the trial. Phase 1b dose-expansion trial. They received mosunetuzumab intravenously every 21 days for a minimum of eight cycles and up to 17 cycles. On the first six cycles, they also were infused with polatuzumab. Both therapies were manufactured by Genentech.

Twenty-two patients participated in the Phase 1b dose-expansion group to determine the maximum tolerated dosage. Another 98 patients participated in the phase 2 dose-expansion group.

Patients with a complete response ended mosunetuzumab after cycle eight. Those with stable disease or partial response at the end of cycle eight continued the drug for 17 cycles.

Half of the patients in the dose-expansion group achieved a complete response rate, meaning their cancer could not be detected. In 59.2% of the patients, their cancers shrunk or disappeared after treatment.

Also in the dose-expansion group, median progression-free survival was 11.4 months and median overall survival was 23.3 months with a median follow-up of 23.9 months. The treatment was administered in the outpatient setting. Cytokine release syndrome, an immune-related side effect, was only seen in 18% of patients and were generally low grade (grade 1: 10.2%; grade 2: 5.1%; grade 3: 3.1%). Other common symptoms were low levels of fatigue and transient low white blood cell count.

"This combination approach produces a favorable safety profile with highly efficacious and durable responses, making it suitable as a new second-line therapy for patients with relapsed or refractory aggressive lymphomas that are not eligible for a stem cell transplant," Budde said.

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About City of Hope
City of Hope's mission is to deliver the cures of tomorrow to the people who need them today. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center at its core, City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hope's growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and treatment facilities in Atlanta, Chicago and Phoenix. City of Hope's affiliated group of organizations includes Translational Genomics Research Institute and AccessHope. For more information about City of Hope, follow us on Facebook, Twitter,YouTube, Instagram and LinkedIn.

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