Novel Anti-BCMA Agent Shows Preliminary Responses in R/R Multiple Myeloma

CT0596, an investigational BCMA-directed CAR T-cell therapy, demonstrated early responses and a manageable safety profile in a small cohort of patients with relapsed/refractory multiple myeloma, according to data from a phase 1 trial (NCT06718270) shared in a poster presentation at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition.¹

With a median follow-up of 4.14 months (range, 0.9-7.9) among 8 evaluable patients who received CT0596, 6 experienced a partial response (PR) or better, including 3 complete responses (CRs) or stringent CRs (sCRs), 1 very good PR (VGPR), and 2 PRs. Additionally, minimal residual disease (MRD) negativity occurred in 6 patients at week 4. One patient with pre-treatment refractory and aggressive disease had progression following study treatment.

One patient experienced an sCR and MRD negativity up until 8 months after starting treatment. Another patient achieved a PR plus a response in extramedullary disease following a second infusion of CT0596. Among patients who received the agent at 4.5 x 10⁸ cells, 1 had an sCR, and another experienced deepening responses over time.

“Preliminary results of this [first-in-human] study of CT0596, an allogenic CAR T-cell therapy targeting BCMA for the treatment of [relapsed/refractory multiple myeloma], demonstrate a manageable safety profile while achieving durable clinical responses,” lead study author Juan Du, MD, PhD, from the Department of Hematology of the Myeloma & Lymphoma Center at Shanghai Changzheng Hospital, Naval Medical University, as well as the Department of Hematology of Ren Ji Hospital at Shanghai Jiao Tong University School of Medicine, wrote with coauthors in the poster. “Additional clinical studies are warranted to further evaluate the clinical utility of CT0596.”

Developers engineered CT0596 as an allogenic BCMA-directed CAR T-cell therapy that makes use of NKG2A, TRAC, and B2M genes to mitigate T or natural killer (NK) cell-mediated graft-versus-host-disease (GVHD) and host immune rejection. The agent also features additional gene editing capabilities to further hinder NK cell-related rejection from the host.

Investigators of this open-label, first-in-human, single-center phase 1 study assessed the safety, tolerability, pharmacokinetics, and preliminary activity of CT0596 among patients with relapsed/refractory multiple myeloma and plasma cell leukemia. Patients received the novel agent at escalating dose levels, including 1.5 x 10⁸, 3.0 x 10⁸, and 4.5 x 10⁸ cells.

The trial’s primary end points included adverse effects (AEs) and the maximum tolerated dose.² Secondary end points included overall response rate, CR and sCR rate, VGPR rate, duration of response, MRD negativity rate, time to response, progression-free survival, and overall survival.

Patients 18 years and older with relapsed/refractory multiple myeloma who received 3 or more prior lines of treatment or with relapsed/refractory plasma cell leukemia who received 1 or more prior lines of therapy were eligible for enrollment on the trial. Other eligibility criteria in the multiple myeloma cohort included having progressive disease on or after the most recent line of treatment, measurable disease, and an ECOG performance status of 0 or 1.

The median patient age was 63.5 years (range, 49-70), and an even proportion of patients were male (50%) and female (50%). Most patients had Revised International Staging System stage II disease (62.5%), prior autologous stem cell transplantation (62.5%), a full lymphodepletion dose (75.0%), and treatment with CT0596 at 3.0 x 10⁸ cells (62.5%).

All patients (100%) had any-grade treatment-emergent AEs (TEAEs), grade 3 or higher AEs, and treatment-related TEAEs. The most common grade 3 or higher toxicities included leukopenia (100%), neutropenia (87.5%), lymphopenia (87.5%), thrombocytopenia (37.5%), and anemia (25.0%).

Cytokine release syndrome (CRS) occurred in 50.0% of patients; no patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS) or GVHD. Data showed no AEs leading to withdrawal or death, and investigators reported no dose-limiting toxicities.

References

1. Du J, Jin L, Qiang W, et al. A first-in-human study of CT0596, an allogeneic CAR T-cell therapy targeting BCMA, in patients with relapsed/refractory multiple myeloma. Blood. 2025;146(suppl 1):2296. doi:10.1182/blood-2025-2296
2. A study of CT0596 in relapsed/refractory multiple myeloma and relapsed/​refractory plasma cell leukemia. ClinicalTrials.gov. Updated December 12, 2024. Accessed December 19, 2025. https://tinyurl.com/2mvcb6sz