Results from the Phase I, Open-Ended Study on BCMA/CD19 Dual-targeting Fast CAR-T GC012F

CAR-T therapy study in patients with relapsed and refractory multiple myeloma

Dr. Juan Du describes the results of the first open-label study of BCMA- and CD19-targeting CAR-T therapy in patients with relapsed and refractory multiple myeloma. The study investigated a second-generation CAR-T therapy called GC012F, which targets both BCMA and CD19, and showed promising results in terms of safety and efficacy. The therapy demonstrated a high overall response rate of 93%, with a significant number of patients achieving minimal residual disease (MRD) negativity. The median duration of response was 38 months, and the therapy showed activity even in high-risk and heavily pre-treated patients.

• GC012F is a second-generation CAR-T therapy that targets both BCMA and CD19, which are markers expressed on multiple myeloma cells.
• The therapy utilizes a dual specificity approach to maximize efficacy by targeting both antigens simultaneously.
• GC012F showed stable CAR expansion and effective functionality, leading to deep and durable responses.
• The study was a multi-center, open-label, single-arm investigator-initiated trial (IIT) that treated 29 patients with GC012F.
• The primary endpoint of the study was overall response rate (ORR), and secondary endpoints included minimal residual disease (MRD) assessment and progression-free survival (PFS), among others.
• 90% of the patients had a high-risk profile according to M-Smart S3 criteria, indicating a poor prognosis.
• 97% of the patients were heavily pre-treated, with 93% being refractory to their last therapy.
• The therapy demonstrated an ORR of 93%, with 38% of patients achieving MRD negativity.
• 89.6% of patients achieved very good partial response (VGPR) or better, with a median duration of response of 38 months.
• 100% of available patients achieved MRD negativity at a sensitivity level of 10^-6.
• In the 12-month analysis, nearly 80% of patients assessed by EuroFlow achieved MRD negativity.
• Patients who achieved MRD negativity at 12 months had longer progression-free survival.
• The safety profile of GC012F was similar to previous findings, with the most common adverse events being cytokine release syndrome (CRS) and neurologic events.
• CRS was observed in 40% of patients, with no grade 4 or 5 CRS events.
• The most common hematologic adverse events were neutropenia, lymphopenia, leukopenia, and thrombocytopenia.
• Pharmacokinetic analysis showed adequate exposure to GC012F in patients, with a persistent and detectable CAR-T level.
• GC012F demonstrated a fast and durable response, with decreased CAR-T persistence observed after 12 months.
• The study concludes that GC012F has a favorable safety profile and high overall response rate, especially in high-risk patients.
• The therapy showed a high rate of MRD negativity, indicating deep and durable responses.
• GC012F demonstrated promising activity in relapsed and refractory multiple myeloma, including highly pre-treated patients.

Authors:
Juan Du, Wei-Jun Fu, Hua Jiang, Baoxia Dong, Li Gao, Li Liu, Jian Ge, Aili He, Lu Li, Jing Lu, Xiequn Chen, Jia Liu, Qi Zhang, Jiaping He, Lianjun Shen, Lihong Weng, Hua Zhang, Wei Cao, Wenling Li

Clinical trial information: NCT04236011; NCT04182581