CRISPR Delivered Anti-BCMA Car-T Therapy for Relapsed or Refractory Multiple Myeloma

Description

PRIMARY OBJECTIVES:

Dose Escalation:

I. To evaluate the safety and toxicity of administering Chimeric Antigen Receptor T Cells (CAR-T) cells targeting BCMA to participants with Relapsed or Refractory Multiple Myeloma (RRMM).

II. To determine the maximum tolerated dose (MTD) for anti-BCMA CAR-T cells.

Dose Expansion:

III. Determine whether administering conforming CAR T-cell product targeting BCMA to participants with RRMM increases the overall response rate (ORR) compared with historical data for non-CAR agents per International Myeloma Working Group (IMWG) response criteria.

IV. Determine whether administering conforming CAR T-cell product targeting BCMA to participants with RRMM lowers the Grade 2 or greater neurologic events to <10% in RRMM.

SECONDARY OBJECTIVES:

Dose Expansion:

I. To describe the efficacy of conforming CAR-T cell product targeting BCMA in participants with RRMM.

II. To evaluate the feasibility of manufacturing anti-BCMA CAR T-cells locally and ability to produce adequate quantities of vector positive T-cells.

III. To evaluate the safety and toxicity of conforming CAR-T cell product targeting BCMA to participants with RRMM.

EXPLORATORY OBJECTIVES:

I. To determine the degree and impact of CAR-T persistence following anti-BCMA CAR-T cell infusion, on clinical outcomes and safety.

II. Describe changes in health-related quality of life (HRQoL) using the European Organization for Research and Treatment of Cancer – Quality of Life C30 questionnaire (EORTC-QLQ-C30).

III. To describe the efficacy of CAR-T cells targeting BCMA in participants with relapsed or refractory BCMA+ RRMM who were treated with product that did not meet one or more pre-specified release criteria (non-conforming product cohort).

OUTLINE:

Participants in both cohorts will undergo leukapheresis, receive lymphodepleting chemotherapy and then receive a single infusion of BCMA CAR-T therapy. After completion of study treatment, participants are followed up at 30, 60 and 90 days, 6 and 12 months, and then yearly for up to 15 years.