A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma.

Abstract

B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies have shown efficacy in relapsed/refractory multiple myeloma (RRMM). Because the non-human originated antigen-targeting domain may limit clinical efficacy, we developed a fully human BCMA-specific CAR, CT103A, and report its safety and efficacy in a phase 1 trial. Eighteen consecutive patients with RRMM, including 4 with prior murine BCMA CAR exposures, were enrolled. CT103A was administered at 1, 3, and 6 × 106 CAR-positive T cells/kg in the dose-escalation phase, and 1 × 106 CAR-positive T cells/kg in the expansion cohort. The overall response rate was 100%, with 72.2% of the patients achieving complete response or stringent complete response. For the 4 murine BCMA CAR-exposed patients, 3 achieved stringent complete response, and 1 achieved a very good partial response. At 1 year, the progression-free survival rate was 58.3% for all cohorts and 79.1% for the patients without extramedullary myeloma. Hematologic toxicities were the most common adverse events; 70.6% of the patients experienced grade 1 or 2 cytokine release syndromes. No immune effector cell-associated neurotoxicity syndrome was observed. To the cutoff date, CAR transgenes were detectable in 77.8% of the patients. The median CAR transgene persistence was 307.5 days. Only 1 patient was positive for the anti-drug antibody. Altogether, CT103A is safe and highly active in patients with RRMM and can be developed as a promising therapy for RRMM. Patients who relapsed from prior murine BCMA CAR T-cell therapy may still benefit from CT103A. This trial was registered at http://www.chictr.org.cn as #ChiCTR1800018137.

• Authors: Di Wang, Jue Wang, Guang Hu, Wen Wang, Yi Xiao, Haodong Cai, Lijun Jiang, Li Meng, Yongkun Yang, Xiaoxi Zhou, Zhenya Hong, Zheng Yao, Min Xiao, Liting Chen, Xia Mao, Li Zhu, Jin Wang, Lugui Qiu, Chunrui Li, Jianfeng Zhou
• Journal: Blood (Blood) Vol. 137 Issue 21 Pg. 2890-2901 (05 27 2021) ISSN: 1528-0020 [Electronic] United States
• PMID: 33512480 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by The American Society of Hematology.

Chemical References

• Antibodies, Anti-Idiotypic
• Antineoplastic Agents
• B-Cell Maturation Antigen
• CT103A chimeric antigen receptor
• Receptors, Chimeric Antigen
• Single-Chain Antibodies
• TNFRSF17 protein, human

Topics

• Adult
• Afibrinogenemia (etiology)
• Aged
• Animals
• Antibodies, Anti-Idiotypic (biosynthesis)
• Antineoplastic Agents (therapeutic use)
• B-Cell Maturation Antigen (antagonists & inhibitors, immunology)
• Combined Modality Therapy
• Drug Resistance, Neoplasm
• Female
• Hematologic Diseases (etiology)
• Humans
• Immunity, Humoral
• Immunotherapy, Adoptive (adverse effects)
• Leukemia, Plasma Cell (etiology, therapy)
• Male
• Mice
• Middle Aged
• Multiple Myeloma (drug therapy, therapy)
• Receptors, Chimeric Antigen (administration & dosage, immunology, therapeutic use)
• Remission Induction
• Single-Chain Antibodies (immunology, therapeutic use)
• Transgenes