AZD0120 / AstraZeneca - LARVOL DELTA

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 (ASH 2025) - P1/2 | "Whileadvances such as BCMA-directed CAR T-cell therapy have improved outcomes, challenges persist,including disease relapse, treatment toxicities (CRS, ICANS, and non-ICANS neurotoxicities), and access.AZD0120 (formerly GC012F) is a first-in-class autologous BCMA/CD19 dual-targeting CAR T-cell therapyusing the FasTCAR rapid manufacturing platform that preserves the naive and central memory T-cellphenotypes with marked in vivo proliferative capacity...The median age was 64 y (range 44–78), median pLOT was 4 (range 3–7), 72% were triple-classrefractory, 20% had prior BCMA CAR T-cell therapy, 4% had prior teclistamab, 28% had high-riskcytogenetic features [del(13q), del(17p13), t(4; 14), t(14; 16), amp(1q)], and 8% had extramedullaryplasmacytomas...Median timeto CRS onset (DL1/DL2) was 9 d (range 2–11), with a median duration of 2 d (range 1–4); 12 pts (48%)received tocilizumab for CRS management and 12% received dexamethasone... Preliminary phase 1b results..."

CAR T-Cell Therapy • Clinical • P1/2 data • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Immunology • Multiple Myeloma • Plasmacytoma

A dual targeting BCMA and CD19 fastcar-t (GC012F/AZD0120) as first-line therapy for newly diagnosed multiple myeloma (ASH 2025) - P1, P1/2 | "Here, we report the combined data of these twostudies to provide long term follow up data of GC012F/AZD0120 in NDMM pts.Methods Eligible NDMM pts received a single infusion of GC012F/AZD0120 following two cycles lenalidomide,bortezomib and dexamethasone (RVd) induction therapy...GC012F/AZD0120 was administered at 4 dose levels:1x105/kg (n=1), 1.5x105/kg (n=3), 2x105/kg (n=4), or 3x105/kg (n=22) after a standard 3-daylymphodepletion regimen of fludarabine and cyclophosphamide...3 pts were treated with one dose of tocilizumab and 1 pt was treated with one dose oftocilizumab and corticosteroids...These promising results highlight the potential ofGC012F/AZD0120 CAR-T therapy for treating NDMM patients with HR features and transplant ineligibleNDMM pts. Further research with a larger patient population and extended follow-up is needed tovalidate these findings and address this critically unmet medical need."

Clinical • Hematological Malignancies • Inflammation • Multiple Myeloma • Plasmacytoma • PLAAT3

AURORA: A Study of AZD0120 in Autoimmune Diseases (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Myositis • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Sclerosis

AZD0120’s first pivotal trial will test settings as early as the second line. (ApexOnco OncologyPipeline) - "Durga-4 will enroll multiple myeloma patients as early as after just one prior line of therapy."

Trial status • Multiple Myeloma

DURGA-4: A Phase III, Open-label, Randomised, Multicentre Study to Evaluate AZD0120 in Participants With Relapsed Refractory Multiple Myeloma. (clinicaltrials.gov) - P3 | N=508 | Not yet recruiting | Sponsor: AstraZeneca

New P3 trial • Hematological Malignancies • Multiple Myeloma • Oncology

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 (TCT-ASTCT-CIBMTR 2026) - P1/2 | "AZD0120 (formerly GC012F) is a first-in-class autologous BCMA/CD19 dual-targeting CAR T-cell therapy using the FasTCAR rapid manufacturing platform...Median time to CRS onset (DL1/DL2) was 9 d (range 2–11); 12 pts (48%) received tocilizumab to manage CRS... Preliminary phase 1b results demonstrated AZD0120 was well tolerated, with a low incidence of serious AEs, no grade ≥3 CRS, and no ICANS. FasTCAR-manufactured AZD0120 had controlled in vivo expansion leading to a predictable safety profile. A single infusion of AZD0120 achieved early, deep responses with 100% MRD negativity in triple-class ‒ exposed pts with RRMM."

CAR T-Cell Therapy • Clinical • IO biomarker • P1/2 data • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Immunology • Multiple Myeloma

AZD0120 Demonstrates Favorable Safety Profile in Phase1b Trial for People With Multiple Myeloma (Blood Cancers Today) - "'Preliminary Phase 1b data suggest that AZD0120, a FasTCAR-manufactured dual BCMA/CD19 CAR T-cell therapy, is well tolerated with no severe CRS or neurotoxicity and shows encouraging deep responses (100% ORR and high MRD negativity) in heavily pretreated relapsed/refractory multiple myeloma. The early safety and efficacy signal is promising, but longer follow-up and larger cohorts are essential to assess durability and comparative benefit versus existing single BCMA-directed therapies,' said Mehdi H. Hamadani, MD..."

Media quote

Updated results of a multicenter first-in-human study of BCMA/CD19 dual-targeting fast CAR-T GC012F for patients with relapsed/refractory multiple myeloma (RRMM). (ASCO 2022) - P1 | "BCMA-CD19 dual FasT CAR-T GC012F continues to provide deep and durable responses with a favorable safety profile in additional RRMM pts across all dose levels demonstrating a very high MRD negativity rate including in pts refractory to anti-CD38, PI and IMIDs. GC012F is currently being studied in earlier lines of therapy as well as additional indications."

Clinical • P1 data • Hematological Malignancies • Infectious Disease • Inflammation • Leukemia • Multiple Myeloma • Novel Coronavirus Disease • Oncology • Transplantation • CD19

CAR-T Therapy Targeting CD19 and BCMA in Highly Sensitized Kidney Transplant Participants (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Tongji Hospital

IO biomarker • New P1 trial • Chronic Kidney Disease • Nephrology • Renal Disease • Transplantation • CXCL8 • IFNG • IL12A • IL13 • IL4 • SDC1

Phase I Open-Label Single-Arm Study of BCMA/CD19 Dual-Targeting FasTCAR-T Cells (GC012F) As First-Line Therapy for Transplant-Eligible Newly Diagnosed High-Risk Multiple Myeloma (ASH 2022) - P1/2 | "Twelve pts received 2 cycles induction therapy of bortezomib, lenalidomide and dexamethasone (VRd), and one patient received 1 cycle bortezomib, epirubicin, and dexamethasone (PAD) and 1 cycle VRd prior to the infusion. GC012F was administered as a single infusion at 3 doses levels (DL) of 1x105/kg, 2x105/kg, or 3x105/kg, after receiving a conditioning chemotherapy consisting of cyclophosphamide and fludarabine...Conclusion In this phase I study for transplant-eligible newly diagnosed high-risk MM, BCMA-CD19 dual FasTCAR-T GC012F showed a very favorable safety profile, high efficacy with 100% ORR and 100% MRD negativity. The promising preliminary results warrants further assessment of GC012F for TE NDMM with more patients and longer follow-up."

CAR T-Cell Therapy • Clinical • P1 data • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • Transplantation • CD19

Updated results of a phase I, open-label study of BCMA/CD19 dual-targeting fast CAR-T GC012F for patients with relapsed/refractory multiple myeloma (RRMM). (ASCO 2023) - P1 | "The updated results showed GC012F continues to provide deep and durable responses, and a very high MRD negativity ratein RRMM pts, including in pts refractory to anti-CD38, PIs and IMIDs. Based on these promising results of the study of GC012F for RRMM, further clinical studies will be conducted to confirm the efficacy of GC012F. Clinical trial information: NCT04236011; NCT04182581."

Clinical • Bone Marrow Transplantation • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • Transplantation

A PHASE I OPEN-LABEL SINGLE-ARM STUDY OF DUAL TARGETING BCMA AND CD19 FASTCAR-T (GC012F) AS FIRST-LINE THERAPY FOR TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED HIGH-RISK MULTIPLE MYELOMA (EHA 2024) - P1/2 | "Consistent with the previous RRMM cohort treated with GC012F, initial data from this study demonstrated thatGC012F resulted in deep and durable response in TE HR NDMM pts with a very favorable safety profile. Allthree dose groups achieved MRD negativity and 100% ORR. The promising preliminary results achieved withGC012F demonstrate the potential of CAR-T therapy in treating NDMM pts."

Clinical • P1 data • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • Transplantation

Updated Results of a Phase I Open-Label Single-Arm Study of Dual Targeting BCMA and CD19 Fastcar-T Cells (GC012F) As First-Line Therapy for Transplant-Eligible Newly Diagnosed High-Risk Multiple Myeloma (ASH 2023) - P1/2 | "Of the 22 pts, 21 pts received 2 cycles induction therapy of bortezomib, lenalidomide and dexamethasone (VRd), and one patient received 1 cycle bortezomib, epirubicin, and dexamethasone (PAD) and 1 cycle VRd prior to the infusion. GC012F was administered as a single infusion at 3 doses levels (DL) of 1x105/kg (n=1), 2x105/kg (n=4), or 3x105/kg (n=17), after a standard 3-day lymphodepletion consisting of cyclophosphamide and fludarabine...The promising preliminary results achieved with GC012F demonstrate potential of CAR-T therapy in newly-diagnosed MM pts. Further research with larger patient population and longer follow-up shall bring the hope to this unmet medical need."

CAR T-Cell Therapy • Clinical • P1 data • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • Transplantation

B-Cell Maturation Antigen/CD19 Dual-Targeting Immunotherapy in Newly Diagnosed Multiple Myeloma. (PubMed, JAMA Oncol) - "The findings of this single-arm, open-label phase 1 cohort study suggest that GC012F may be a safe treatment associated with positive health and survival outcomes for patients with high-risk NDMM eligible for transplant. Owing to the small sample size, further studies with larger cohorts and longer follow-up durations are needed."

Journal • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • Transplantation

GC012F Injection in Refractory Idiopathic Inflammatory Myopathy (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Daishi Tian | Not yet recruiting ➔ Recruiting

Enrollment open • Myositis

ZENITH: An Open-label Study of AZD0120 in Adults With Multiple Sclerosis (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting | N=18 ➔ 24

Enrollment change • Enrollment open • CNS Disorders • Multiple Sclerosis

A Study of GC012F Injection in Subjects With Refractory Systemic Lupus Erythematosus (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Gracell Biotechnologies (Shanghai) Co., Ltd. | Phase classification: P1/2 ➔ P1 | N=118 ➔ 18

Enrollment change • Phase classification • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

AURORA: A Study of AZD0120 in Autoimmune Diseases (clinicaltrials.gov) - P1 | N=27 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial • Immunology • Inflammatory Arthritis • Myositis • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Sclerosis

ALACRITY: A phase 1b/2 study of AZD0120 (BCMA/CD19 CAR-T cell therapy) in participants with relapsed or refractory light chain amyloidosis (AL) (ASH 2025) - P1/2 | "Daratumumab+CyBorD (cyclophosphamide, bortezomib, dexamethasone) is approved to treat newly diagnosed AL (ANDROMEDA study), with improved outcomes...This study is registered on ClinicalTrials.gov (NCT07081646). Conclusion This study aims to determine the safety, tolerability, and efficacy of AZD0120 in adult participants with relapsed or refractory AL."

CAR T-Cell Therapy • P1/2 data • Amyloidosis • Hematological Malignancies • Hepatology • Leukemia • Liver Failure • Multiple Myeloma

AZD0120 (GC012F), a BCMA/CD19 dual-targeting fastcar T-cell therapy, demonstrates potent preclinical efficacy in multiple myeloma (ASH 2025) - "The FasTCAR-based AZD0120, designed to target BCMA and/or CD19 and maximize in vivo expansion, demonstrated potent, dose-dependent, and antigen-specific cytotoxicity both in vitro and in vivo. The superior antitumor function of AZD0120 versus GC012C suggests benefit of the FasTCAR manufacturing platform and supports continued development of AZD0120 as a promising therapeutic option for pts with MM."

CAR T-Cell Therapy • IO biomarker • Preclinical • Hematological Malignancies • Multiple Myeloma • CXCR4 • IFNG

One-year follow-up of CD19/BCMA dual-targeting fastcar-T GC012F (AZD0120) therapy in patients with refractory systemic lupus erythematosus (ASH 2025) - P1/2 | "Patients not in remission still hadimproved disease activity. An ongoing phase 1/2 trial (NCT06530849) is further evaluating its safety andefficacy in a larger cohort."

Clinical • Glomerulonephritis • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Rheumatology • Systemic Lupus Erythematosus

AstraZeneca advances haematology and cell therapy ambition with largest-ever presence at ASH (AstraZeneca Press Release) - "Investigational T-cell engager, surovatamig, and CAR T-cell therapy, AZD0120, will show potential with initial data across multiple blood cancers; New results will showcase benefit of Calquence in patients with mantle cell lymphoma and chronic lymphocytic leukaemia."

Clinical data • B Acute Lymphoblastic Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma

Preliminary findings from the Phase Ib portion of the Phase Ib/II DURGA-1 trial were reported at the American Society of Hematology (ASH) meeting (Firstwordpharma Press Release) - "Of 15 efficacy-evaluable patients — 10 receiving dose level 1, and 5 at dose level 2 — the overall response rate was 100%; three patients in the dose level 1 cohort and two in the dose level 2 cohort experienced a complete response (CR). The median time to response for both dosages was 0.9 months. Five patients in the low dose and three receiving the high dose of AZD0120 were evaluable for minimal residual disease (MRD); all were MRD-negative as measured by next-generation sequencing."

P1 data • Multiple Myeloma

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) - P1 | N=64 | Recruiting | Sponsor: AstraZeneca | N=20 ➔ 64

Enrollment change • Hematological Malignancies • Multiple Myeloma • Oncology

Study of GC012F, CAR-T Therapy Targeting CD19 and BCMA in Chinese Participants With Relapsed or Refractory AL Amyloidosis (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: Gracell Biotechnologies (Shanghai) Co., Ltd.

New P1 trial • Amyloidosis