City of Hope Physicians and Scientists Present New Immunotherapy Research at ASCO Virtual Conference

June 3, 2021 13:00 UTC

Immunotherapy treatments for multiple myeloma and brain tumors will be featured

DUARTE, Calif.--(BUSINESS WIRE)-- City of Hope physicians and scientists will present updated research on a potential immunotherapy for multiple myeloma, a study on chimeric antigen receptor (CAR) T cell therapy for brain tumors and an investigational drug for advanced urothelial carcinoma, among other studies on leading-edge cancer treatments, during the 2021 American Society of Clinical Oncology’s (ASCO) Annual Meeting. The meeting takes place virtually June 4 to 8.

“City of Hope’s commitment to investigating and delivering the most effective cancer therapies to our patients is bolstered by scientific learnings and discussions that take place each year at the ASCO conference,” said Steven T. Rosen, M.D., City of Hope’s chief scientific officer. “Our faculty look forward to sharing their findings and engaging with the diverse audiences at ASCO, as well as learning about the latest research on cancer prevention, detection and treatment that could ultimately improve outcomes for patients.”

New immunotherapy drug effective against relapsed/recurrent multiple myeloma

A new type of therapy – bispecific antibody T-cell engagers – are being studied at City of Hope and are showing promising results against multiple myeloma, a blood cancer that is diagnosed in almost 35,000 Americans each year.

Teclistamab targets the BCMA protein on multiple myeloma cells and also directs CD3+ T cells against BCMA-expressing cancerous cells.

“Bispecific antibody therapy engages the patient’s own immune system to fight cancer, and directly targets the myeloma cell, providing a double dose of powerful action against multiple myeloma cells,” said Amrita Krishnan, M.D., City of Hope director, Judy and Bernard Briskin Center for Multiple Myeloma Research and the lead investigator of the immunotherapy study.

Krishnan will present updated results of patients treated with the recommended Phase 2 dose in the first-in-human Phase 1 study of teclistamab.

Approximately 160 patients received the therapy. The overall response rate in 40 patients treated with the Phase 2 dose was 65%. Fifty-eight percent of patients achieved a “very good” partial response or better, and 40% achieved a complete response or stringent complete response, which is a deeper response category used for multiple myeloma patients.

Side effects included mild cytokine release syndrome and neutropenia. There were no dose-limiting toxicities at the Phase 2 dose level.

Krishnan concluded that the therapy at the recommended Phase 2 dose level was well-tolerated and showed encouraging efficacy. Patients’ responses appear durable and deepened over time.

“Our research supports further investigation of teclistamab as a therapy on its own and in combination with other therapies,” Krishnan added.

Updated data on abstract no. 8007 will be presented during an oral presentation at the ASCO conference on Tuesday, June 8, 8 to 11 a.m. EDT.

Predicting how CAR T cell therapy may work against brain tumors

A team of City of Hope scientists and researchers conducted a study using artificial intelligence to predict treatment response and survival in brain tumor patients.

The team evaluated the data from 60 patients with high-grade glioma who participated in a Phase 1 City of Hope clinical trial in which they underwent surgical resection and CAR T cell therapy. The team developed an explainable machine learning model that used clinical, molecular and radiomic data to predict overall survival in patients treated with CAR T cell therapy. (Radiomic data is a type of imaging.)

They also used such features as age, gender, race, ethnicity, histology, tumor grade, the expression of the IL-13 receptor alpha 2 (IL-13Rα2), a protein found on brain tumor cells, tumor location and other factors in the model.

The team was able to predict how a patient would respond to CAR T cell therapy. They found that patients with a larger tumor surface area and volume, as well as older age, had reduced survival, while patients with more IL-13Rα2 and tumor sphericity had increased survival.

The model also allowed researchers to place patients in two groups: those who had a higher risk of the cancer progressing and those who had a lower risk.

"Our model can potentially be used to optimize clinical trial enrollment through more precise patient screening and treatment planning," said Chi Wah “Alec” Wong, Ph.D., lead data scientist and the abstract’s lead author.

"Our long-term goal is continued optimization of the model for validation and application in a more diverse population," said Ammar Chaudhry, M.D., City of Hope assistant clinical professor, Department of Diagnostic Radiology and the lead investigator for the glioblastoma CAR T imaging biomarker study. “Once validated, this model has the potential to be applied across different tumor types treated with CAR T and other cell therapies.”

Behnam Badie, M.D., City of Hope neurosurgeon and The Heritage Provider Network Professor in Gene Therapy, and Christine Brown, Ph.D., City of Hope deputy director, T Cell Therapeutics Research Laboratory, and The Heritage Provider Network Professor in Immunotherapy, also contributed to the research.

Updated data on abstract no. 104 will be presented in a clinical science symposium during the ASCO conference on Sunday, June 6, 11:30 a.m. to 12:45 p.m. EDT.

ATR inhibitor not effective when combined with standard chemotherapy for patients with advanced urothelial carcinoma

The standard frontline chemotherapy regimen for patients with metastatic urothelial cancer is cisplatin and gemcitabine but could those therapies, combined with an ATR inhibitor, produce better clinical outcomes?

Led by City of Hope’s Sumanta K. Pal, M.D., an open-label, randomized Phase 2 study was conducted in 23 centers nationwide to test whether the combination of cisplatin with gemcitabine and berzosertib, a selective ATR inhibitor, could improve clinical outcomes. The ATR inhibitor is a first-in-class therapy that prevents repair of DNA strands damaged within cancer cells. The trial was conducted through Experimental Therapeutics Clinical Trials Network.

A total of 87 patients (median age 67) took part in the trial. Forty-one patients received cisplatin/gemcitabine alone and 46 received the chemotherapies with berzosertib.

Median progression free survival was 8.0 months for both groups. The response rate was 54% in the chemotherapy/berzosertib arm and 63% in patients who only received chemotherapy. Median overall survival was shorter with chemotherapy/berzosertib as compared to patients who only received chemotherapy (14.4 months versus 19.8 months). There were higher rates of thrombocytopenia and neutropenia in the chemotherapy/berzosertib group compared to chemotherapy alone.

Pal concluded that there was no improvement in progression-free survival with the addition of berzosertib to the chemotherapy, and a trend toward inferior survival was observed. These results suggest caution in reducing the starting dose of cytotoxic therapy to accommodate addition of a myelosuppressive agent.

“Cisplatin and gemcitabine remain the standard of care for metastatic urothelial carcinoma,” said Pal, City of Hope clinical professor, Department of Medical Oncology & Therapeutics Research, and co-director, Kidney Cancer Program.

Reducing the dose of the chemotherapy regimen to accommodate for hematological toxicities that could be caused by berzosertib may have reduced the therapeutic combination’s effectiveness, Pal added.

Final data on abstract no. 4507 will be presented in an oral presentation during the ASCO conference on Monday, June 7, 8 to 11 a.m. EDT.

About City of Hope

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hope’s translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin, monoclonal antibodies, and numerous breakthrough cancer drugs are based on technology developed at the institution. Translational Genomics Research Institute (TGen) became a part of City of Hope in 2016. AccessHope™, a wholly owned subsidiary, was launched in 2019, dedicated to serving employers and their health care partners by providing access to City of Hope’s exceptional cancer expertise. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is ranked among the nation’s “Best Hospitals” in cancer by U.S. News & World Report. Its main campus is located near Los Angeles, with additional locations throughout Southern California and in Arizona. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

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Letisia Marquez

Source: City of Hope

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