On February 15, 2022 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported that City of Hope Phase 1 clinical trial data on MB-105, a prostate stem cell antigen ("PSCA") chimeric antigen receptor ("CAR") T-cell therapy administered systemically to patients with PSCA-positive metastatic castration-resistant prostate cancer ("mCRPC"), has been selected for a poster presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Genitourinary ("GU") Cancers Symposium taking place February 17-19, 2022, both virtually and in San Francisco (Press release, Mustang Bio, FEB 15, 2022, View Source [SID1234608134]).
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The primary objectives of the Phase 1 clinical trial are to define the dose limiting toxicity ("DLT"), identify a recommended Phase 2 dose and describe preliminary bioactivity and efficacy. To date, 12 patients have been treated at City of Hope, one of the largest cancer research and treatment organizations in the United States, with a median age of 68 (42-72). Dosing began at 100 million ("M") cells without lymphodepletion chemotherapy, then lymphodepletion consisting of fludarabine and cyclophosphamide was added to 100M cells prior to dose escalation to a planned maximum of 600M cells. Three patients were treated at the 100M cell dose with no DLTs. In the 100M cells plus lymphodepletion dose level, two patients experienced DLT of grade 3 non-infective cystitis and fatigue. The protocol was amended to reduce the cyclophosphamide dose and to intensify the monitoring with early intervention for cystitis.
No DLT occurred in three patients treated in the modified lymphodepletion 100M cell cohort. Cytokine release syndrome occurred in four patients, none with higher than Grade 2. The Response Evaluation Criteria in Solid Tumors ("RECIST") of the 12 patients included seven stable disease patients and five progressive disease patients. PSA declines (one >90%) were seen as well as radiographic improvement, though RECIST response was limited to stable disease by concurrent bone metastases. Correlative studies indicated bioactivity of PSCA CAR T-cells.
The results indicate that PSCA-CAR T-cell therapy is feasible in patients with mCRPC with DLT of cystitis, and show preliminary anti-tumor effect at a dose of 100M cells plus lymphodepletion. It was concluded that escalation up to the next dose level of 300M can proceed in the trial.
Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "The Phase 1 data to be presented by Dr. Dorff on behalf of the City of Hope team demonstrate the potential of Mustang’s MB-105 as a PSCA-targeted CAR T-cell therapy for prostate cancer. There is a potential to apply this therapy in other solid tumors that express PSCA. We remain encouraged by the ongoing progress of this trial as we develop our pipeline of cell therapy treatments for patients with cancers that are difficult to treat."
Details of the presentation are as follows:
Title: Phase 1 study of PSCA-targeted chimeric antigen receptor (CAR) T cell therapy for metastatic castration resistant prostate cancer (mCRPC)
Abstract Number: 91
Dates and Times: Poster Session A: Prostate Cancer, February 17, 2022; 11:30 a.m. – 1:00 p.m.; 5:45 – 6:45 p.m.
Presenter: Tanya Dorff, M.D., City of Hope Associate Clinical Professor, Department of Medical Oncology & Experimental Therapeutics and Section Chief of City of Hope’s Genitourinary Disease Program
For more information, please visit the ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium website.
About MB-105 (PSCA CAR T technology)
MB-105 was developed in the laboratory of Saul Priceman, Ph.D., assistant professor in City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation and associate director of translational sciences in the T Cell Therapeutics Research Laboratory led by Stephen Forman, M.D., Director of City of Hope’s Hematologic Malignancies Research Institute and the Laboratory’s Director.
The Phase 1 clinical trial of MB-105 will continue to enroll up to 33 patients. Its primary endpoints are to define safety and optimal dosing of PSCA CAR T cells in treating patients with PSCA-positive mCRPC. Secondary endpoints include assessing the expansion and persistence of PSCA CAR T cells, the clinical response based on Prostate Cancer Working Group 3 (PCWG3) criteria, survival outcomes and serum cytokine profiles in peripheral blood pre- and post-therapy, as well as describing the PSCA expression level on tumor cells prior to CAR T cell infusion and the relationship it may have with disease response and associated toxicities. For more information on this Phase 1 trial, please visit www.clinicaltrials.gov using identifier NCT03873805.