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

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 • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Movement Disorders • Multiple Myeloma • Oncology • Ophthalmology • Rare Diseases

CC-95266-MM-001: A Study of CC-95266 in Participants With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=130 | Completed | Sponsor: Juno Therapeutics, a Subsidiary of Celgene | Active, not recruiting ➔ Completed

Trial completion • Hematological Malignancies • Multiple Myeloma • Oncology

Trial in Progress: QUINTESSENTIAL—a Phase 2 study of Arlocabtagene Autoleucel (arlo-cel) in Patients with relapsed/refractory Multiple Myeloma (RRMM) (TCT-ASTCT-CIBMTR 2026) - P1, P2 | "This phase 2 study will evaluate the efficacy and safety of arlo-cel in patients with RRMM and ≥3 pLOT. Describe the phase 2 trial in progress, QUINTESSENTIAL (NCT06297226), that will evaluate the efficacy and safety of arlocabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma. Inform about the key inclusion criteria of QUINTESSENTIAL: age ≥18 years, confirmed diagnosis of MM per International Myeloma Working Group (IMWG) criteria, ≥4 classes of MM treatment (including immunomodulatory drugs, proteasome inhibitors, anti ‑ CD38 antibodies, and anti-BCMA therapies), and ≥3 prior lines of therapy."

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

Trial in Progress: QUINTESSENTIAL-2—a phase 3 Study of Arlocabtagene Autoleucel Versus Standard of Care in Adult Patients with Relapsed and Refractory Multiple Myeloma (RRMM) Exposed to Lenalidomide (TCT-ASTCT-CIBMTR 2026) - P3 | "Eligible pts must have prior LEN exposure (with ≥2 consecutive cycles, unless best response of progressive disease to LEN-containing treatment or in cases of LEN intolerance or unacceptable toxicity) and will be randomized 1:1 to Arm A or Arm B. Arm A includes leukapheresis within 3-4 days of randomization, bridging therapy of DPd (daratumumab, pomalidomide, dexamethasone) or Kd (carfilzomib, dexamethasone) per investigator choice within 6 days of randomization, and lymphodepleting chemotherapy prior to a single arlo-cel infusion. This phase 3 study will compare the efficacy and safety of arlo-cel vs SOC in adult pts with RRMM refractory to LEN. Describe the phase 3 trial in progress, QUINTESSENTIAL-2 (NCT06615479), that will compare the efficacy and safety of arlocabtagene autoleucel vs standard of care in adult patients with relapsed/refractory multiple myeloma who are exposed to lenalidomide. Inform about the key inclusion criteria of QUINTESSENTIAL-2: age ≥18..."

Clinical • First-in-human • IO biomarker • P3 data • Hematological Malignancies • Multiple Myeloma

Clinical Activity of BMS-986393 (CC-95266), a G Protein–Coupled Receptor Class C Group 5 Member D (GPRC5D)–Targeted Chimeric Antigen Receptor (CAR) T Cell Therapy, in Patients with Relapsed and/or Refractory (R/R) Multiple Myeloma (MM): First Results from a Phase 1, Multicenter, Open-Label Study (ASH 2022) - P1 | "After screening and leukapheresis, pts received bridging therapy if needed, then lymphodepleting chemotherapy (fludarabine 30 mg/m2 + cyclophosphamide 300 mg/m2 daily for 3 days) followed by a single infusion of BMS-986393... At all tested dose levels, BMS-986393 demonstrated a favorable safety profile; both CRS and neurotoxicity were low-grade, and neurotoxicity was infrequent and short-lived. Dose escalation is ongoing; MTD has not been exceeded. Preliminary efficacy appeared promising; antitumor responses were observed, including pts with CR who were MRD-negative at month 3."

Clinical • IO biomarker • P1 data • Bone Marrow Transplantation • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Plasmacytoma • Thrombocytopenia • Transplantation • 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

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 • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Movement Disorders • Multiple Myeloma • Neutropenia • Oncology • Ophthalmology • Plasmacytoma • Rare Diseases • Thrombocytopenia • GPRC5D

BMS-986393 (CC-95266), A G PROTEIN–COUPLED RECEPTOR CLASS C GROUP 5 MEMBER D (GPRC5D)–TARGETED CAR T-CELL THERAPY FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): RESULTS FROM A PHASE 1 STUDY (EHA 2023) - P1 | "Dose escalation of BMS-986393 from 25 through 450 × 10 6 CAR T cells has not exceeded the MTD at the time of data cutoff. Observed CRS was mostly G1/2. ICANS-type neurotoxicity was infrequent, low-grade, and reversible."

CAR T-Cell Therapy • IO biomarker • P1 data • Anemia • Bone Marrow Transplantation • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immune Modulation • Multiple Myeloma • Neutropenia • Oncology • Plasmacytoma • Thrombocytopenia • Transplantation • 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

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

BMS-986393 (CC-95266), a G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted CAR T-cell therapy for relapsed/refractory multiple myeloma (RRMM): results from a phase 1 study (IMW 2023) - P1 | "As of data cutoff, dose escalation of BMS-986393 from 25–450 × 10⁶ CAR T cells did not exceed MTD. CRS was mostly G1/2. ICANS-type neurotoxicity was infrequent, low-grade and reversible."

CAR T-Cell Therapy • IO biomarker • P1 data • Anemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Plasmacytoma • Thrombocytopenia • GPRC5D

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 • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Movement Disorders • Multiple Myeloma • Oncology • Rare Diseases

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

Assessment of pharmacodynamic efficacy biomarkers from A phase 1, first-in-human study of arlocabtagene autoleucel (arlo-cel) in relapsed and refractory multiple myeloma (RRMM) (ASH 2025) - P1, P2, P3 | "Efficacy and pharmacodynamic data from this first-in-human phase 1 study demonstratethat arlo-cel led to deep responses in RRMM, even in patients with high BL tumor burden. Increasedclearance of sBCMA after arlo-cel treatment was associated with deeper clinical response and sBCMAnadir levels were prognostic of longer landmark PFS. The relationship between robust CAR T-cellexpansion and reduced sBCMA nadir levels reinforces that arlo-cel drove the observed deep therapeuticresponses."

Biomarker • Clinical • First-in-human • IO biomarker • P1 data • PK/PD data • Hematological Malignancies • Multiple Myeloma

Trial in progress: QUINTESSENTIAL-2—a phase 3 study of arlocabtagene autoleucel versus standard of care in adult patients with relapsed and refractory multiple myeloma (RRMM) exposed to lenalidomide (ASH 2025) - P3 | "Eligible pts will berandomized 1:1 to Arm A or Arm B. Pts randomized to Arm A will have leukapheresis within 3-4 days ofrandomization, bridging therapy of DPd (daratumumab, pomalidomide, dexamethasone) or Kd(carfilzomib, dexamethasone) per Investigator choice within 6 days of randomization, andlymphodepleting chemotherapy prior to a single infusion of arlo-cel. This is a trial in progress and isexpected to enroll 440 pts at ~126 sites globally across North America, South America, Europe, Asia, andAustralia. The first patient was enrolled in March 2025."

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

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

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