AZD0120 Displays Early Responses/Manageable Safety in R/R Multiple Myeloma

There were no deaths, grade 4 or higher infections, or dose-limiting toxicities observed with AZD0120 in the phase 1b/2 DURGA-1 trial.

AZD0120, a dual BCMA and CD19-targeted CAR T-cell therapy, displayed early responses and a manageable safety profile in addition to a quick manufacturing turnaround time among a small cohort of patients with relapsed/refractory multiple myeloma, according to preliminary findings from the phase 1b/2 DURGA-1 study (NCT05850234) presented in an oral session at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition.1

At the time of the data cutoff date for the presentation, which was October 1, 2025, the median follow-up was 3.9 months.1 The overall response rate with AZD0120 across 2 dose levels (n = 23) was 96%, with a median time to response of 28 days. The complete response (CR) and stringent CR (sCR) rate with AZD0120 was 78.3% and the partial response (PR) rate was 17.4%. In patients with previous exposure to a BCMA-targeted CAR T cell (n = 5), the ORR was 100% with AZD0120 with a CR/sCR rate of 80%. The MRD negativity rate (<10-5) was 94%, for those evaluable for minimal residual disease (MRD) assessment at 1 month (n = 17).

“A single infusion of AZD0120 resulted in early and deep responses. Response deepens over time and were seen in BCMA-naive and -exposed patients,” lead investigator Shambavi Richard, MD, from the Icahn School of Medicine at Mount Sinai, in New York, New York, said during a presentation of the results. “The safety profile is well-suited for outpatient administration, with 35% of patients receiving infusion outpatient.” Richard is an associate professor of medicine (Hematology and Medical Oncology) with the Center of Excellence for Multiple Myeloma, and director of CAR T-cell Research and Stem Cell Transplant for Multiple Myeloma.

AZD0120 Manufacturing Process

AZD0120 is a next-generation CAR T cell created using the FasTCAR rapid manufacturing platform. In this process, the cells are manufactured in less than 3 days, Richard noted. “This rapid manufacturing is facilitated by elimination of ex vivo expansion,” she said. “The cells go through activation and transduction, and all expansion occurs in vivo, resulting in younger and fitter T cells.”

The median time for manufacturing was 14 days from apheresis to release (range, 10-30) and 28 days from apheresis to infusion (range, 19-44). After infusion, the median time to peak cell expansion was 13 days. CAR T persistence was seen at day 56 for 100% of patients.

At the beginning of the study, the manufacturing was completed externally but transitioned to an in-house approach in March 2025, with a 100% manufacturing success rate following the shift. “The next-generation platform is established for AZD0120, with a reliable turnaround time,” said Richard.

Patient Characteristics and DURGA-1 Study Design

In the study, after enrollment, patients underwent apheresis followed by lymphodepletion with fludarabine and cyclophosphamide at 5, 4, and 3 days prior to infusion of the CAR T-cell product. Bridging or debulking therapy were permitted as needed. AZD0120 was infused at 2 dose levels for 26 patients. Dose-level 1 (DL1) was 1 x 105 cells/kg and was received by 12 patients and DL2 was 3 x 105 cells/kg was received by 14 patients.

The median age of patients was 63 years (range, 44-78) and the median time from diagnosis was 6.7 years (range, 1.8-13.8). Extramedullary plasmacytomas were present in 1 patient (4%). The most common International Staging System disease stage was III (62%) and 35% of patients had 1 or more high-risk cytogenetic abnormality. The most common high-risk feature was amp1q21 (23%), followed by t4;14 (8%), t14:16 (8%), and del17p (4%).

The median prior lines of therapy were 4 (range, 3-7) and 85% of patients had received a prior autologous stem cell transplant. Seven patients (27%) received bridging therapy. Prior BCMA therapy was permitted in the study, with 5 patients having received a prior BCMA-targeted CAR T-cell therapy and 1 patient having received a BCMA T-cell engager. For those receiving a prior CAR T-cell therapy, the median time since treatment was 2.6 years (range, 1.9-4.8), and for the T-cell engager, it was 0.6 years. Eighty-eight percent of patients were refractory to their last treatment, and 69% were triple-class refractory.

AZD0120 Safety Profile in DURGA-1

There were no deaths, grade 4 or higher infections, or dose-limiting toxicities observed with AZD0120. Across both dose levels, the most observed grade 3/4 adverse effects (AEs) were neutrophil count decrease (81%), lymphocyte count decrease (50%), white blood cell count decrease (42%), anemia (23%), platelet count decrease (19%), infection (8%), febrile neutropenia (8%), and hypotension (8%).

Across both doses, 62% of patients experienced cytokine release syndrome (CRS). At DL1, CRS occurred in 75% (n = 9) of patients compared with 50% for DL2 (n = 7). For DL1, all events were grade 1 in severity. For DL2, CRS was grade 1 for 6 of the patients and grade 2 for 1. The median onset to CRS was 9 days and the median duration was 1.5 days. Tocilizumab (Actemra) was administered to 46% of patients and dexamethasone was administered to 12%. One patient received anakinra.

There were no cases of immune effector cell–associated neurotoxicity syndrome (ICANS) in the DL1 group compared with 1 case of grade 1 ICANS in the DL2 cohort. Richard added that there were no delayed neurotoxicities, Parkinsonism, cranial nerve palsies, or Guillain-Barré syndrome.

“CRS onset was predictable at a median of 9 days, consistent with peak in vivo expansion at 13 days,” Richard said.

Next Steps for AZD0120

AZD0120 is being explored in multiple clinical trials including a phase 1b/2 study for amyloid light chain amyloidosis (NCT07081646)3 and another phase 1 open-label study for multiple myeloma (NCT07073547).4 The CAR T-cell therapy is also the subject of studies for multiple sclerosis (NCT07224373) and lupus (NCT06897930).

References

1. Richard S, Gaballa M, Gregory T, et al. Safety and efficacy of AZD0120, a BCMA/CD19 dual-targeting CAR T-cell therapy, in relapsed/refractory multiple myeloma: Preliminary results from the DURGA-1 phase 1b/2 study. Blood. 2025;146(suppl 1):269. doi:10.1182/blood-2025-269
2. A study of GC012F (AZD0120), a CAR T therapy targeting CD19 and BCMA in subjects with relapsed/refractory multiple myeloma. ClinicalTrials.gov. Updated August 6, 2025. Accessed December 8, 2025. https://www.clinicaltrials.gov/study/NCT05850234
3. A phase 1b/2 study of CAR T cell therapy targeting CD19 and BCMA in participants with relapsed or refractory AL amyloidosis. (ALACRITY). ClinicalTrials.gov. Updated September 19, 2025. Accessed December 8, 2025. https://www.clinicaltrials.gov/study/NCT07081646
4. A phase I, open-label, multicenter study to evaluate the safety, tolerability, cellular kinetics, immunogenicity, pharmacodynamics, and preliminary efficacy of AZD0120 in participants with multiple myeloma. ClinicalTrials.gov. Updated December 3, 2025. Accessed December 8, 2025. https://www.clinicaltrials.gov/study/NCT07073547