arlocabtagene autoleucel (BMS-986393) / BMS - LARVOL DELTA

QUINTESSENTIAL-2: A phase 3 study comparing efficacy and safety of arlocabtagene autoleucel (arlo-cel) versus standard regimens in adult patients with relapsed or refractory multiple myeloma (RRMM) refractory to lenalidomide (DGHO 2025) - P3 | "Arm A: single infusion of arlo-cel (RP2D of 150 × 106 CAR T cells), including leukapheresis within 3 days of randomization, bridging therapy of DPd (daratumumab, pomalidomide, dexamethasone) or Kd (carfilzomib, dexamethasone) per Investigator within 3 days of leukapheresis, and lymphodepleting chemotherapy prior to arlo-cel infusion. Secondary endpoints include overall survival, ORR, MRD negative status, complete response rate, time to response, duration of response, pharmacokinetics, patient-reported quality of life outcomes, and safety.Pts receiving arlo-cel will be followed for ≤5 years after the last patient is randomized, with a long-term follow-up study (≤15 years post infusion). The trial is expected to enroll 440 pts across 111 global sites, with first patient enrollment planned for Feb 2025."

Clinical • IO biomarker • P3 data • Hematological Malignancies • Multiple Myeloma

Trial in progress: A phase 1 study to evaluate the safety and preliminary efficacy of arlocabtagene autoleucel (arlo-cel), a GPRC5D-targeted chimeric antigen receptor (CAR) T cell therapy, in combination with mezigdomide (MEZI) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) (ASH 2025) - P1 | "Statistical analysis details will be finalized in thestatistical analysis plan. Enrollment began in February 2024 and is ongoing."

Clinical • Combination therapy • P1 data • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • GPRC5D • IKZF1

Trial in progress: QUINTESSENTIAL—a phase 2 study of arlocabtagene autoleucel (arlo-cel) in patients with relapsed/refractory multiple myeloma (RRMM) (ASH 2025) - P1, P2 | "This is a trial inprogress and will recruit at ~47 centers across the USA, Canada, and Japan. The first patient first visit wasachieved on March 21, 2024."

Clinical • IO biomarker • P2 data • Hematological Malignancies • Multiple Myeloma • GPRC5D

THE IMPACT OF CAR-T IN MULTIPLE MYELOMA (SIE 2025) - P3 | "In the absence of a randomized head-to-head comparison among ide-cel and cilta-cel, a retrospective, multicenter, analysis of 586 pts treated with either cilta-cel or ide-cel showed the superiority of Cilta-cel vs ide-cel in terms of response rates, PFS and OS, though associated with a more burdensome toxicity profile in terms of high-grade CRS, delayed neurotoxicity, and infections.7Anitocabtagene autoleucel (anito-cel, previously known as CART-ddBCMA) is an anti-BCMA CAR T-cell construct modeled to express a D-domain binder between the CD8 hinge-region and the transmembrane domain...Also, long-term safety data revealed a manageable profile, supporting BMS-986393 as a potential treatment for RRMM and further research (e.g., the ongoing phase II QUINTESSENTIAL study.10Interestingly, preliminary data from patients with 1-3 prior lines of therapy including a PI and an IMiD are also encouraging, with high rates of response that deepened over time and no new safety..."

Hematological Malignancies • Infectious Disease • Multiple Myeloma • CD8

QUINTESSENTIAL: Study of Arlocabtagene Autoleucel (BMS-986393) a GPRC5D-directed CAR T Cell Therapy in Adult Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=230 | Recruiting | Sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company | N=175 ➔ 230

Enrollment change • Hematological Malignancies • Multiple Myeloma • Oncology

Trial in Progress: QUINTESSENTIAL-2—A Phase 3 Study of Arlocabtagene Autoleucel vs Standard of Care in Adult Patients with Relapsed and Refractory Multiple Myeloma (RRMM) Refractory to Lenalidomide (IMS 2025) - P3 | "Pts randomized to Arm-A will receive a single infusion of arlo-cel, including leukapheresis within 3 days of randomization, bridging therapy of DPd (daratumumab, pomalidomide, dexamethasone) or Kd (carfilzomib, dexamethasone) per Investigator choice within 3 days of leukapheresis, and lymphodepleting chemotherapy prior to arlo-cel infusion. This phase 3 study will compare the efficacy and safety of arlo-cel versus SOC in adult pts with RRMM who are refractory to lenalidomide."

Clinical • IO biomarker • P3 data • Hematological Malignancies • Multiple Myeloma

Trial in Progress: QUINTESSENTIAL—A Phase 2 Study of Arlocabtagene Autoleucel (arlo-cel) in Triple- and Quad-Class Exposed Patients With Relapsed and Refractory Multiple Myeloma (RRMM) (IMS 2025) - P1, P2 | "This phase 2 study will evaluate the efficacy and safety of arlo-cel in heavily pretreated pts with RRMM."

Clinical • IO biomarker • P2 data • Hematological Malignancies • Multiple Myeloma • GPRC5D

Long-term Follow-Up of a Phase 1 Study of Arlocabtagene Autoleucel (arlo-cel; BMS-986393) in Patients With Heavily Pretreated Relapsed/Refractory Multiple Myeloma (RRMM) (IMS 2025) - P1 | "Maturing data from the phase 1 study demonstrate a safety profile consistent with previous disclosures and deep and durable responses following a single infusion of arlo-cel. These data, demonstrating comparable efficacy between 75í—106 and 150í—106 doses of arlo-cel, suggest that both doses have a favorable benefit-risk profile in RRMM."

Clinical • P1 data • Hematological Malignancies • Multiple Myeloma

Arlocabtagene autoleucel, a GPRC5D-Targeted CAR T-Cell Therapy for Patients With Relapsed/Refractory Multiple Myeloma: Updated Phase 1 Safety and Efficacy Results in Patients With 1–3 Prior Regimens (IMS 2025) - P1 | "A single administration of arlo-cel at the RP2D in pts with RRMM and 1–3 prior lines of therapy was well tolerated and led to a high response rate that deepened over time, with few early relapses after 15.8 mo median follow-up. The favorable benefit-risk profile for this dose and population was consistent with prior disclosures. Notably, frequency and grade of infections were improved over some BCMA-targeted therapies."

CAR T-Cell Therapy • Clinical • P1 data • Ataxia • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Movement Disorders • Multiple Myeloma • Rare Diseases

Multiple Myeloma Unpacked (ICML 2025) - P3 | "Several other phase II studies have explored the efficacy of triplet regimens incorporating Rd as a backbone, combined with agents such as elotuzumab [30], ixazomib [31], or carfilzomib [32] as well as quadruplet regimen including daratumumab and carfilzomib [33]...The landscape of induction treatment has evolved with the incorporation of the anti-CD38 monoclonal antibody daratumumab (D) into the triplet bortezomib-thalidomide-dexamethasone (VTd) and, more recently, bortezomib-lenalidomide-dexamethasone (VRd)...In transplant-ineligible patients, VRd [45], daratumumab-lenalidomide-dexamethasone (DRd) [46, 47] and daratumumab-bortezomib-melphalan-prednisone (DVMP) [48, 49] have been the standards of cares for years...The FDA approval of isatuximab-bortezomib-lenalidomide-dexamethasone (Isa-VRd), based on the results of the IMROZ study [38], which demonstrated the superiority of Isa-VRd over VRd in terms of MRD negativity and PFS, introduces a new SoC...Consequently,..."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma • Smoldering Multiple Myeloma • B2M • CRBN • CTCs • XPO1

Trial in Progress: Quintessential-2A—A Phase 3 Study of Arlocabtagene Autoleucel Versus Standard of Care in Adult Patients With Relapsed and Refractory Multiple Myeloma Refractory to Lenalidomide (SOHO 2025) - P3 | "Arm-A: single infusion of arlo-cel, including leukapheresis within 3 days of randomization, bridging therapy of DPd (daratumumab, pomalidomide, dexamethasone) or Kd (carfilzomib, dexamethasone) per investigator within 3 days of leukapheresis, and lymphodepleting chemotherapy prior to arlo-cel infusion. Reused with permission. This abstract was accepted and previously presented at the 2025 ASCO Annual Meeting."

Clinical • IO biomarker • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology

Trial in Progress: Quintessential—A Phase 2 Study of Arlocabtagene Autoleucel in Triple- and Quad-Class Exposed Patients With Relapsed and Refractory Multiple Myeloma (SOHO 2025) - P1, P2 | "Reused with permission. This abstract was accepted and previously presented at the 2025 ASCO Annual Meeting."

Clinical • P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

CC-95266-MM-001: A Study of CC-95266 in Participants With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=180 | Active, not recruiting | Sponsor: Juno Therapeutics, a Subsidiary of Celgene | Trial completion date: Jun 2025 ➔ Dec 2025 | Trial primary completion date: Jun 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

TRIAL IN PROGRESS: QUINTESSENTIAL-2—A PHASE 3 STUDY OF ARLOCABTAGENE AUTOLEUCEL VERSUS STANDARD OF CARE IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM) REFRACTORY TO LENALIDOMIDE (EHA 2025) - P3 | "Additional inclusion criteria include confirmed MM diagnosis per International Myeloma Working Group criteria, measurable disease during screening, and Eastern Cooperative Oncology Group performance status 0 or 1.Eligible patients will be randomized 1:1 to one of 2 treatment arms: Arm A or Arm B. Patients randomized to Arm A will receive a single infusion of arlo-cel (RP2D of 150 × 106 CAR T cells), including leukapheresis within 3 days of randomization, bridging therapy of DPd (daratumumab, pomalidomide, dexamethasone) or Kd (carfilzomib, dexamethasone) per Investigator choice within 3 days of leukapheresis, and lymphodepleting chemotherapy prior to arlo-cel infusion. This phase 3 study will compare the efficacy and safety of arlo-cel versus SOC in adult patients with RRMM who are refractory to lenalidomide."

Clinical • IO biomarker • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology

TRIAL IN PROGRESS: QUINTESSENTIAL – A PHASE 2 STUDY OF ARLOCABTAGENE AUTOLEUCEL (ARLO-CEL) IN TRIPLE- AND QUAD-CLASS EXPOSED PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM) (EHA 2025) - P1, P2 | "This phase 2 study will evaluate the efficacy and safety of arlo-cel in heavily pretreated patients with RRMM."

Clinical • IO biomarker • P2 data • Hematological Malignancies • Multiple Myeloma • Oncology • GPRC5D

Assessment of normal plasma cell biomarkers after arlocabtagene autoleucel (arlo-cel) treatment in patients with ≥3L relapsed refractory multiple myeloma (MM). (ASCO 2025) - P1, P2 | " Clinical endpoints included treatment-emergent adverse events for patients treated with arlo-cel (NCT04674813; n = 84) and idecabtagene vicleucel (ide-cel, NCT03361748; n = 137). Arlo-cel patients had higher levels of uiFLC from months 2–6, demonstrating greater anti-tumor specificity and preservation of humoral immunity. As a result, arlo-cel has the potential to achieve lower rates of hypogammaglobulinemia and infections compared to BCMA-targeting therapies, with fewer interventions."

Biomarker • Clinical • IO biomarker • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • GPRC5D

QUINTESSENTIAL: A multicenter phase 2 study evaluating the efficacy and safety of arlocabtagene autoleucel (arlo-cel) in triple- and quad-class exposed patients with relapsed or refractory multiple myeloma (RRMM). (ASCO 2025) - P1, P2 | "This study will recruit at 47 centers across the USA, Canada, and Japan. The first pt first visit was achieved on March 21, 2024."

Clinical • IO biomarker • P2 data • Hematological Malignancies • Multiple Myeloma • Oncology • GPRC5D

QUINTESSENTIAL-2: A phase 3 study comparing efficacy and safety of arlocabtagene autoleucel (arlo-cel) versus standard regimens in adult patients with relapsed or refractory multiple myeloma (RRMM) refractory to lenalidomide. (ASCO 2025) - P3 | "Arm A: single infusion of arlo-cel (RP2D of 150 × 106 CAR T cells), including leukapheresis within 3 days of randomization, bridging therapy of DPd (daratumumab, pomalidomide, dexamethasone) or Kd (carfilzomib, dexamethasone) per Investigator within 3 days of leukapheresis, and lymphodepleting chemotherapy prior to arlo-cel infusion. Pts will be followed for ≤5 years after the last patient is randomized, with a subsequent long-term follow-up study (≤15 years post infusion) for pts receiving arlo-cel. The trial is expected to enroll 440 pts across 111 sites globally, with first patient enrollment planned for Feb 2025."

Clinical • IO biomarker • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology

A Study to Compare the Efficacy and Safety of BMS-986393 Versus Standard Regimens in Adult Participants With Relapsed or Refractory and Lenalidomide-refractory Multiple Myeloma (QUINTESSENTIAL-2) (clinicaltrials.gov) - P3 | N=440 | Recruiting | Sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

QUINTESSENTIAL: Study of BMS-986393 a GPRC5D-directed CAR T Cell Therapy in Adult Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company | Trial completion date: Jun 2030 ➔ Jun 2032 | Trial primary completion date: Oct 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Efficacy and Safety with Extended Follow-up in a Phase 1 Study of BMS-986393, a G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D)-Targeted CAR T Cell Therapy, in Patients (pts) with Heavily Pretreated Relapsed/Refractory (RR) Multiple Myeloma (MM) (ASH 2024) - P2 | "These data support BMS-986393 as a potential treatment for heavily pretreated RRMM, which is being investigated in the ongoing phase 2 QUINTESSENTIAL study (NCT06297226). The presentation will report updated data after ~ 18 months' follow-up, including the first overall survival data."

CAR T-Cell Therapy • Clinical • P1 data • Ataxia • Bone Marrow Transplantation • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Movement Disorders • Multiple Myeloma • Oncology • Ophthalmology • Rare Diseases

Arlo-cel Elicits 87% ORR in Heavily Pretreated, Relapsed/Refractory Multiple Myeloma (OncLive) - P1 | N=180 | CC-95266-MM-001 (NCT04674813) | Sponsor: Juno Therapeutics | "The GPRC5D-targeting CAR T-cell therapy arlocabtagene autoleucel also yielded a 53% complete response rate in relapsed/refractory multiple myeloma....In the overall efficacy-evaluable population (n = 79), the overall response rate (ORR) was 87%, which comprised a 53% complete response (CR) rate, a 23% very good partial response (VGPR) rate, and an 11% partial response (PR) rate. In patients who were treated with the recommended phase 2 dose (RP2D) of 150 × 106 CAR T cells (n = 23), the ORR was 91%, the CR rate was 48%, and the VGPR and PR rates were both 22%. Forty-two percent of patients in the overall population and 35% of patients in the RP2D population achieved a stringent CR (sCR)."

P1 data • Multiple Myeloma

BMS-986393, a G Protein–Coupled Receptor Class C Group 5 Member D (GPRC5D)-Targeted CAR T Cell Therapy, in Patients (pts) with Relapsed/Refractory (RR) Multiple Myeloma (MM) and 1–3 Prior Regimens: Updated Phase 1 Safety and Efficacy Results (ASH 2024) - "Most (90%) had MM refractory to the most recent regimen; 90% had lenalidomide-refractory, 55% triple-class refractory, and 6% penta-class refractory MM. These data support BMS-986393 as a potential early-line treatment in RRMM. The trial is ongoing and a further update with longer follow-up will be presented."

CAR T-Cell Therapy • Clinical • P1 data • Ataxia • Bone Marrow Transplantation • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Movement Disorders • Multiple Myeloma • Oncology • Rare Diseases

Bristol Myers Squibb’s Presentations at ASH 2024 Reinforce Strength of Hematology Portfolio and Scientific Advances in Differentiated Research Platforms (Businesswire) - "Bristol Myers Squibb...announced the presentation of more than 90 data disclosures, including 18 oral presentations, across company-sponsored studies, investigator-sponsored studies and collaborations from its hematology and cell therapy research programs at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, to be held from December 7 to 10 in San Diego, California."

Clinical data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Multiple Myeloma • Small Lymphocytic Lymphoma

First Disclosure of Phase 1 Efficacy and Safety Results of arlocabtagene autoleucel (BMS-986393): Abstract #922 (Businesswire) - P1 | N=111 | NCT06121843 | Sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company | "After a median follow-up of 16.1 months (range, 2.8-25.2) in efficacy-evaluable patients (n= 79), arlo-cel demonstrated durable responses, with ORR maintained at 87%. MRD was evaluated as an exploratory endpoint, and 57% (48/84) of patients were MRD-evaluable. Results showed that 46% (22/48) of patients were MRD-negative and had a CR/stringent CR (sCR). In all treated patients, 27% (23/84) were MRD-negative and achieved a CR. Median PFS was 18.3 months (95% CI: 11.8-21.9) and median OS was not reached. Treatment-related adverse events (TRAEs), specifically hematological adverse events (AEs), were most common in patients, with neutropenia occurring in 62 (74%) patients. Overall, 69 patients (82%) had CRS. Three patients had macrophage activation syndrome/hemophagocytic lymphohistiocytosis, and ICANS occurred in eight patients."

Cytokine release syndrome • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology