CT103A, Human BCMA-Targeting CAR-T Cell In Relapsed/Refractory Multiple Myeloma

CT103A, designed with a fully human BCMA-specific CAR structure, has demonstrated durable efficacy and safety in patients with relapsed and refractory multiple myeloma who have been severely pretreated. Researchers presented updated efficacy and safety information from its phase 1b/2 study (FUMANBA-1) with extended follow-up duration. The study aimed to assess the efficacy, tolerability, and PK/PD of CT103A. In China, FUmanba-1 was conducted in 14 centers. They enrolled RRMM patients who received at least three prior lines of therapy containing a proteasome inhibitor and an immunomodulatory agent and were resistant to their last line of treatment. Patients who had progressed during prior BCMA CAR-T cell therapy were also included.

All patients received a single infusion of CT103A containing 1.0 x 106 CAR-T cells per kilogram. About 103 patients [53.4% male; median age 58.0 years (range 39-70)] with RRMM received CT103A as of September 9, 2022 (17 in phase 1b; 86 in phase 2), with a median follow-up of 13.8 months (range 0.4 to 27.0). Before treatment, a median of four (range: 3-23) lines of therapy was administered to the patients. About 101 were eligible for effectiveness evaluation. The median response time was 16 days (11-179). There was a 96% ORR with a 74.3% CR. The median DOR and PFS have yet to be reached. The PFS rate at one year was 78.8% (95% CI: 68.6–85.97). For patients (N=89) without prior BCMA CAR-T therapy, the ORR was 98.9%, with a CR of 78.7%. For patients (N=81) without initial BCMA CAR-T therapy who had received CT103A for more than 6 months as of the cutoff date, the ORR was 98.8%, with 80.2% CR. For patients with prior BCMA CAR-T cell therapy, four out of five (80%) of those who achieved sCR maintained sCR 18 months after the initial infusion. All 101 patients with CR/sCR were MRD-negative, with a median delay to MRD-negativity of 14 days (range: 13-185). Additionally, 82.4% (95%CI: 70.90-89.72%) maintained MRD negativity over 12 months. Since the last publication at the 64th ASH meeting, no new CRS or ICAN events have occurred. The most frequent AEs grade 3 related to treatment were still hematologic.

In a median of 12 days, CT103A attained a peak level of 87,570.6 copies/μg gDNA.CT103A remained above the lower limit of qualification (100 copies/μg gDNA) in 50.0% (28/56) of patients 12 months after infusion and in 40% (4/10) of patients 24 months after information. In addition, only 20 of 103 patients (19.4%) with evaluable samples were found to have anti-drug antibodies. At a longer median follow-up of 13.8 months, CT103A induced profound and durable responses in patients with MM who were severely pretreated. In addition, patients with prior BCMA CAR-T cell therapy who achieved sCR maintained sCR for 18 months. CT103A exhibited a favorable safety profile, with no novel risks observed after a more extended observation period.

Source: https://library.ehaweb.org/eha/2023/eha2023-congress/386696/chunrui.li.ct103a.a.novel.fully.human.bcma-targeting.car-t.cells.in.patients.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27922%2Atrend%3D4016%2Amarker%3D4178

Clinical Trial: https://www.clinicaltrials.gov/study/NCT05066646

Chunrui Li, Di Wang, Yongping Song, He Huang, Jianyong Li, Bing Chen, Jing Liu, Yujun Dong, Kai Hu, Peng Liu, Xi Zhang, Jianqing Mi, Zhenyu Li, Kaiyang Ding, Aining Xu, Songbai Cai, Jingjing Guo, Hongyu Gui, Wen Wang, lugui qiu/CT103A, A NOVEL FULLY HUMAN BCMA-TARGETING CAR-T CELLS IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: UPDATED RESULTS OF PHASE 1B/2 STUDY (FUMANBA-1)/Inc, M. G. (n.d.). CT103A, A NOVEL FULLY HUMAN BCMA-TARGETING CAR-T CELLS IN PATIENTS… by Prof. Dr. Chunrui Li. Library.ehaweb.org. Retrieved July 14, 2023, from https://library.ehaweb.org/eha/2023/eha2023-congress/386696/chunrui.li.ct103a.a.novel.fully.human.bcma-targeting.car-t.cells.in.patients.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27922%2Atrend%3D4016%2Amarker%3D4178