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. (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

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

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

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

BMS-986393 Shows First-In-Class Potential in Relapsed/Refractory Multiple Myeloma (OncLive) - P1 | N=180 | NCT04674813 | Sponsor: Juno Therapeutics, a Subsidiary of Celgene | "A single infusion of treatment with the autologous GPRC5D-targeted CAR T-cell therapy BMS-986393 led to high responses that deepened over time in patients with relapsed/refractory multiple myeloma who received between 1 and 3 prior lines of therapy, according to data from the phase 1 CC-95266-MM-001 trial (NCT04674813) that were presented at the 21st International Myeloma Society Annual Meeting....At a median follow-up of 5.3 months (range, 2.0-9.3), the objective response rate (ORR) in evaluable patients (n = 24) was 96%, which included a stringent complete response rate (sCR) of 37.5%, CR rate of 4.2%, very good partial response rate of 33.3%, and partial response rate of 20.8%. The median time to response was 1.0 month (range, 0.9-2.9), and the median duration of response was not reached."

P1 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 | Not yet recruiting | Sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

CAR T-Cell Therapy • New P3 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Safety and preliminary efficacy of BMS-986393, a GPRC5D CAR T cell therapy, in patients (pts) with relapsed/refractory (RR) multiple myeloma (MM) and 1–3 prior regimens: results from a phase 1 study (IMW 2024) - P1 | "Around half (52%) had prior stem cell transplantation; 71% had received anti-CD38 therapy; 90% were lenalidomide-refractory; 55% were triple-class refractory; 90% had MM refractory to the last regimen, and 3% had prior B-cell maturation antigen (BCMA)-targeted therapy. Initial results suggest that a single infusion of BMS-986393 is safe and has promising preliminary efficacy in pts with RRMM and 1–3 prior regimens. While follow-up is limited, the safety profile of BMS-986393 at 150 x 106 CAR T cells was favorable with no new safety signals. High response rates were achieved."

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

QUINTESSENTIAL: a multicenter phase 2 study evaluating the efficacy and safety of BMS-986393 in patients with quadruple-class exposed relapsed or refractory multiple myeloma (IMW 2024) - P1, P2 | "NA"

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

SAFETY AND PRELIMINARY EFFICACY OF BMS-986393, A GPRC5D CAR T CELL THERAPY, IN PATIENTS WITH RELAPSED/REFRACTORY (RR) MULTIPLE MYELOMA (MM) AND 1–3 PRIOR REGIMENS: FIRST RESULTS FROM A PHASE 1 STUDY (EHA 2024) - P1 | "After leukapheresis, pts received lymphodepleting chemotherapy (fludarabine/cyclophosphamide) followed bya single infusion of BMS​986393 150 × 106 CAR T cells...One pt (3%) had a prior BCMA-targeted therapy (belantamab mafodotin)... Initial results suggest a single infusion of BMS-986393 is safe and demonstrates promising preliminary efficacyin pts with MM and 1–3 prior regimens. While follow-up is limited, the safety profile of BMS-986393 at 150 x106 CAR T cells was favorable with no new safety signals. High response rates were achieved."

CAR T-Cell Therapy • Clinical • P1 data • Bone Marrow Transplantation • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology • Rare Diseases • Transplantation

Omar Nadeem, MD, on Initial Efficacy of GPRC5D-CAR in R/R Multiple Myeloma (CGTLive) - P1 | N=180 | NCT04674813 | Sponsor: Juno Therapeutics, a Subsidiary of Celgene | "Initial data from the phase 1 CC95266MM001 study (NCT04674813) evaluating BMS-986393 were presented at the European Hematology Association 2024 Hybrid Congress, held June 13-16 in Madrid, Spain...The data are from 31 participants in the study who received 150 x 106 CAR T cells. Only 1 patient had received prior anti-BCMA therapy. Investigators found that overall response rate of 96%, with a complete responses rate of 32%, although median follow-up time was only 3.2 months (range, 0.5–5.8) at the time of data cutoff....He noted that follow-up time was short in this data and that responses may deepen as follow-up lengthens."

P1 data • 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 | Not yet recruiting ➔ Recruiting

CAR T-Cell Therapy • 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 | Not yet recruiting | Sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

CAR T-Cell Therapy • New P2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

A Study to Evaluate the Safety, Effectiveness and Tolerable Dose of BMS-986393 in Novel Combinations in Participants With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=111 | Recruiting | Sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review. (PubMed, Blood Cancer J) - "We review the biology and target validation of GPRC5D, and clinical data from early phase trials of GPRC5D-targeting bispecific antibodies, talquetamab and forimtamig, and chimeric antigen receptor T cell (CAR-T) therapies, MCARH109, OriCAR-017, and BMS-986393...Further clinical trials, including those investigating GPRC5D-targeting T-cell-redirecting agents in combination with other anti-myeloma therapies and with different treatment modalities, may help to elucidate the future optimal treatment regimen and sequence for patients with multiple myeloma and improve survival outcomes. Video Summary."

Journal • Review • Dermatology • Hematological Malignancies • Infectious Disease • 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 | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

BMS-986393 (CC-95266), a G Protein–Coupled Receptor Class C Group 5 Member D (GPRC5D)–Targeted Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from a Phase 1 Study (ASH 2023) - P1 | "In this first-in-human study, BMS-986393 showed a manageable safety profile and deep and durable responses, including MRD negativity, at all tested dose levels, including in pts refractory to prior BCMA-directed therapies. CRS and ICANS-type neurotoxicity were mostly low-grade, with increased G ≥ 3 events at the 300 and 450 × 106 CAR T‑cell doses. On-target off-tumor TRAEs, all G1/2, occurred in a minority of pts."

IO biomarker • P1 data • Anemia • Ataxia • Bone Marrow Transplantation • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Movement Disorders • Multiple Myeloma • Neutropenia • Oncology • Ophthalmology • Pain • Plasmacytoma • Rare Diseases • Thrombocytopenia • Transplantation • GPRC5D

Bristol Myers Squibb Announces Data at ASH 2023 from Diverse Multiple Myeloma Pipeline, Underscoring Range of Tailored Treatment Approaches to Address Unique Patient Needs (Businesswire) - P1 | N=180 | NCT04674813 | Sponsor: Juno Therapeutics | "At the data cutoff of September 11, 2023 (median follow-up of 8.8 months), BMS-986393 continued to demonstrate an efficacy benefit with deep and durable responses in these heavily pretreated patients, including those with prior exposure to BCMA-targeted treatment. The overall response rate (ORR) was 91% (48% complete response rate) among patients treated with the recommended Phase 2 dose (RP2D, n=23), including an ORR of 100% (n=8) in patients with previous exposure to anti-BCMA targeting therapy....These early clinical data suggest a single infusion of BMS-986393 is tolerable and efficacious in RRMM, including in those with prior exposure to BCMA-targeted therapy​, and a single-arm Phase 2 trial of BMS-986393 in patients with RRMM exposed to four or more classes of therapy (quadruple-class exposed) is planned to open in the first half of 2024."

New P2 trial • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology