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3468 CD27-Armored BCMA-CAR T Cell (CBG-002) Therapy for Relapsed and Refractory Multiple Myeloma: A Phase I Clinical Trial

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster II
Hematology Disease Topics & Pathways:
Biological therapies, adult, Plasma Cell Disorders, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Therapies, Lymphoid Malignancies, Adverse Events, Study Population, Human
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Yang Xu1,2*, Xuzhao Zhang1*, Dijia Xin1*, Jiawei Zhang1*, Luyao Wang1*, Yili Fan1*, Boxiao Chen1*, Wen Lei1*, Xi Qiu1*, Huawei Jiang1*, Xibin Xiao1*, Liansheng Huang1*, Wenjun Yang3*, Jiangao Zhu3* and Wenbin Qian1*

1The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
2Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University,, Hangzhou, China
3Carbiogene Therapeutics Ltd., Hangzhou, China


Several BCMA CAR T-cell products have been approved for relapsed or refractory multiple myeloma (RRMM), but long-term response has not been established. There is growing interest in the use of next-generation CAR T-cell therapy in RRMM. CBG002 is an armored BCMA CAR T-cell product engineered to constitutively express CD27, which binds CD70 to promote T-cell proliferation and differentiation. In vitro, CBG-002 cells exhibited enhanced proliferation, greater cytotoxicity and a higher proportion of memory T cells compared to control BCMA-CAR T cells; in animal models, CBG-002 infusion also resulted in improved tumor control and prolonged survival in MM xenograft mice. Based on the preclinical data, we conducted a phase I clinical trial to evaluate its safety and efficacy in patients with RRMM.


This is a single-arm, open-label, phase I study (NCT04706936). Key eligibility criteria were RRMM patients who had received at least 3 prior regimens, including a proteasome inhibitor and an immunomodulatory drug; the percentage of BCMA expression ≥50% on myeloma cells, detected by either flow cytometry and immunohistochemistry. Patients received 3 days of fludarabine (30 mg/m2) and cyclophosphamide (300 mg/m2) followed by a single dose of CBG-002 infusion. The dose-escalation study follows a "3+3" design with 1×106/kg, 2×106/kg and 3×106/kg CAR-T cell cohorts. The primary endpoint was safety, including grade 3 or 4 treatment-emergent adverse events (TEAEs) and dose-limiting toxicities (DLTs); The secondary endpoints were overall response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS).


As of June 25, 2023, 12 patients were enrolled and 1 patient was later excluded due to <50% BCMA expression. Among the evaluable 11 patients, there were 9 males and 2 females; median age was 52 years (range 36-66), 5/11 (45.5%) patients had high-risk cytogenetics including complex karyotype, t(4;14),1q21 amplification and del(17p), 4 (36.4%) had extramedullary disease (EMD). The median number of prior treatments was 5 (range 3-7); 7/11 pts were triple-agent exposed and refractory; 5/11 underwent ASCT. The most common TEAEs were neutropenia (G3/4 63.6%), thrombocytopenia (G3/4 36.4%) and anemia (G3/4 45.5%). Nine patients developed G1/2 CRS, which resolved spontaneously except for 2 patients who required steroids and tocilizumab, and no patients developed G3/4 CRS or ICANS. The median time to onset of CRS was 7 days (range 5-21) and the median duration was 6 days (range 5-8). At a median follow-up of 9 months, the ORR was 81.8%, including sCR/CR of 63.6%, VGPR 9.1% and PR 9.1%. After infusion, 8 pts were MRD negative in bone marrow by flow cytometry at day 28, 5 pts continued at month 3. The median OS was 14 months and the OS rate was 100%. The median PFS was 9 months and the PFS rate was 60%. The CBG-002 kinetics paralleled peripheral blood sCD27 levels with a median time to peak of 15 days (range 7-14). The fold increase in sCD27 levels was significantly higher in responders (12.1, range 1.2-83.8) than in non-responders (1.68, range 0.81-9.45).


In this phase I study, CBG-002, a CD27-armored BCMA-CAR T therapy has demonstrated remarkable safety and clinical activity in RRMM patients.

Disclosures: Yang: Carbiogene Therapeutics Ltd.: Current Employment, Current equity holder in private company. Zhu: Carbiogene Therapeutics Ltd.: Consultancy, Current Employment.

*signifies non-member of ASH