Allogeneic CT0596 Shows Early Activity, Safety in R/R Myeloma
CT0596 was well tolerated and showed preliminary efficacy in relapsed/refractory multiple myeloma, early phase 1 data show.
CARsgen Therapeutics plans to submit an investigational new drug application for CT0596 in 2025.
Allogeneic, BCMA-targeted CAR T-cell therapy CT0596 demonstrated a manageable safety profile and early signs of efficacy in patients with relapsed or refractory multiple myeloma, according to findings from a phase 1 trial (NCT06718270).1
Findings announced by CARsgen Therapeutics showed that no dose-limiting toxicities were reported among safety-evaluable patients with multiple myeloma (n = 8). Additionally, no instances of grade 3 or higher cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, or graft-vs-host disease occurred. Adverse effects did not lead to treatment discontinuation in any patients. This patient population had received a median of 3 prior lines of therapy.
Patients who underwent their first efficacy assessment at week 4 (n = 5) achieved a complete response (CR) or stringent CR (sCR) rate of 60% and a minimal residual disease (MRD)–negativity rate of 80%. Two patients evaluated at day 14 experienced reductions in measurable lesions of more than 92% and more than 65%, respectively. Responses were ongoing for all patients who experienced a CR or sCR; 1 responder completed 4 months of follow-up.
Full data will be presented at an upcoming medical conference, and CARsgen Therapeutics intends to submit an investigational new drug application for CT0596 in the second half of 2025.
“Based on the preliminary safety and efficacy data, CT0596 demonstrated favorable tolerability and encouraging efficacy signals in [patients with] relapsed/refractory multiple myeloma across all predefined dose levels, with CAR-T expansion observed,” CARsgen Therapeutics wrote in a news release. “These findings warrant further exploration not only in relapsed/refractory multiple myeloma, but also in other plasma cell malignancies and autoimmune diseases mediated by autoreactive plasma cells.”
The single-arm, open-label, exploratory dose-escalation and dose-finding trial conducted at Shanghai Changzheng Hospital in China is enrolled patients at least 18 years of age with relapsed/refractory multiple myeloma who received at least 3 prior lines of therapy, including at least 1 proteasome inhibitor and at least 1 immunomodulatory drug.2 The study is also including patients with relapsed/refractory plasma cell leukemia who received at least 1 prior line of therapy. Progressive disease following treatment is required for both patient populations.
Other key inclusion criteria comprise measurable disease, a life expectancy of more than 12 weeks, and an ECOG performance status of 0 or 1. Investigators are excluding patients with Waldenström macroglobulinemia, POEMS syndrome, or primary light chain amyloidosis.
Patients are excluded if they have HIV, active hepatitis C, or active hepatitis B; have any uncontrolled active infection; underwent prior allogeneic stem cell transplant at any point or autologous stem cell transplant within 12 weeks of enrollment; received disease-related treatment within 14 days of enrollment; or received cell therapy within 28 days of enrollment. The presence of symptomatic or suspected central nervous system metastases precludes patients from enrollment, and second primary malignancies requiring treatment within the past 2 years or not in complete remission also exclude patients from enrollment.
Enrolled patients are receiving lymphodepleting chemotherapy comprised of fludarabine at 22.5 to 30 mg/m² and cyclophosphamide at 350 to 500 mg/m² prior to receiving a single infusion of CT0596.
Safety and establishing the maximum tolerated dose of CT0596 are the trial’s primary end points. Secondary end points included overall response rate, CR/sCR rate, very good partial response or better rate, duration of response, MRD-negativity rate, time to response, progression-free survival, overall survival, and pharmacokinetics.
References
- CARsgen Announces preliminary clinical data for allogeneic BCMA CAR-T CT0596, demonstrating favorable safety and efficacy. News release. CARsgen Therapeutics. May 12, 2025. Accessed May 12, 2025. https://www.carsgen.com/en/news/20150512/
- A study of CT0596 in relapsed/refractory multiple myeloma and relapsed/refractory plasma cell leukemia. ClinicalTrials.gov. Updated December 12, 2024. Accessed May 12, 2025.
