An Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With High-Risk Multiple Myeloma

NCT03601078 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: BB2121-MM-002U1111-1216-42092023-505183-10
• Study Type: interventional
• Target: 312
• Locations: 6 countries
• Sites: 25

Brief Summary

This study is a multi-cohort, open-label, multicenter Phase 2 study to evaluate the efficacy and safety of bb2121 in participants with relapsed and refractory multiple myeloma (RRMM) (Cohort 1), in participants with RRMM who receive bridging therapy with talquetamab (Cohort 1b), in participants with multiple myeloma (MM) having progressed within 18 months of initial treatment with autologous stem cell transplantation (ASCT) (Cohort 2a) and without ASCT (Cohort 2b) or, in participants with inadequate response post ASCT during initial treatment (Cohort 2c) and the efficacy and safety of bb2121 used in combination with lenalidomide maintenance in participants with suboptimal response post ASCT (Cohort 3). Approximately 248 participants will be enrolled into one of three cohorts. Cohort 1 (including cohort 1b) will enroll approximately 126 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens. Cohort 2a will enroll approximately 39 MM subjects, with 1 prior anti-myeloma therapy including ASCT and with early relapse. Cohort 2b will enroll approximately 39 MM subjects with 1 prior anti-myeloma therapy not including ASCT and with early relapse. Cohort 2c will enroll approximately 30 MM subjects with inadequate response to ASCT during their initial anti-myeloma therapy. The cohorts will start in parallel and independently. Cohort 3 will enroll approximately 30 newly diagnosed multiple myeloma (NDMM) participants with suboptimal response to ASCT.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; bb2121; Relapsed and Refractory Multiple Myeloma; High Risk Multiple Myeloma; Phase 2; Multi-cohort; Open-label

Outcome Measures

Primary Outcomes (2)

• Overall response rate (ORR)- Cohort 1

  Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator

  Up to approximately 5 years (Participants will transition to the long term follow-up (LTFU) study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit)

• Complete response (CR) rate - Cohort 1b, 2a, 2b, 2c, and Cohort 3

  Percentage of subjects who achieved CR or stringent CR according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator

  Up to approximately 5 years (Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit)

Secondary Outcomes (18)

• Complete response (CR) rate - Cohort 1

  Up to approximately 5 years (Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit)

• Overall response rate (ORR) - Cohort 1b, 2a, b, c and Cohort 3

  Up to approximately 5 years (Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit)

• Very good partial response (VGPR) rate - Cohort 2c

  Up to approximately 5 years(Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit)

• Time to response (TTR)

  Up to approximately 5 years (Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit)

• Duration of response (DoR)

  Up to approximately 5 years (Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit)

Study Arms (6)

Cohort 1: BB2121 in relapsed and refractory multiple myeloma participants

EXPERIMENTAL

bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 450 x 10\^6 CAR+ T cells after receiving lymphodepleting chemotherapy

Biological: bb2121

Cohort 1b: BB2121 with talquetamab in relapsed and refractory multiple myeloma participants

EXPERIMENTAL

Biological: bb2121; Drug: Talquetamab

Cohort 2a: BB2121 in multiple myeloma with Autologous stem cell transplantation participants

EXPERIMENTAL

Biological: bb2121

Cohort 2b: BB2121 in multiple myeloma without Autologous stem cell transplantation participants

EXPERIMENTAL

Biological: bb2121

Cohort 2c: BB2121 in multiple myeloma participants with inadequate response post ASCT

EXPERIMENTAL

Biological: bb2121

Cohort 3: BB2121 with lenalidomide maintenance in newly diagnosed multiple myeloma

EXPERIMENTAL

Biological: bb2121; Drug: Lenalomide

Interventions

bb2121 BIOLOGICAL

bb2121 consists of autologous T lymphocytes transduced with an anti-BCMA CAR lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR)

Also known as: BMS-986395

Cohort 1: BB2121 in relapsed and refractory multiple myeloma participants; Cohort 1b: BB2121 with talquetamab in relapsed and refractory multiple myeloma participants; Cohort 2a: BB2121 in multiple myeloma with Autologous stem cell transplantation participants; Cohort 2b: BB2121 in multiple myeloma without Autologous stem cell transplantation participants; Cohort 2c: BB2121 in multiple myeloma participants with inadequate response post ASCT; Cohort 3: BB2121 with lenalidomide maintenance in newly diagnosed multiple myeloma

Lenalomide DRUG

Specified dose on specified days

Also known as: Revlimid®

Cohort 3: BB2121 with lenalidomide maintenance in newly diagnosed multiple myeloma

Talquetamab DRUG

Specified dose on specified days

Also known as: TALVEY

Cohort 1b: BB2121 with talquetamab in relapsed and refractory multiple myeloma participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
• For Cohorts 1 and 2 only, participant has measurable disease, defined as:
• M-protein (serum protein electrophoresis \[sPEP\] or urine protein electrophoresis \[uPEP\]): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours and/or
• Light chain MM without measurable disease in the serum or urine: Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Subjects with one of the following cohort specific requirements:
• Cohort 1 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens:
• Subject must have received at least 3 prior anti-myeloma treatment regimens. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
• Subject must have undergone at least 2 consecutive cycles of treatment for each regimen, unless PD was the best response to the regimen
• Subject must have received prior treatment with a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody
• Subject has evidence of PD on or within 60 days of the most recent prior treatment regimen
• Subject achieved a response (minimal response \[MR\] or better) to at least 1 prior treatment regimen
• Cohort 2 subjects with 1 prior anti-myeloma treatment regimen:
• Subject must have received only 1 prior anti-myeloma treatment regimen. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
• Subject must have the following HR factors:

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Subject used any investigational agents within 14 days prior to leukapheresis or, for Cohort 3, within 14 days prior to consent
• Subject received any of the following within the last 14 days prior to leukapheresis or, for Cohort 3, within 14 days prior to consent:
• Plasmapheresis
• Major surgery (as defined by the investigator)
• Radiation therapy other than local therapy for myeloma associated bone lesions
• Use of any systemic anti-myeloma drug therapy
• Subject with known central nervous system involvement with myeloma
• Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation
• History or presence of clinically relevant central nervous system (CNS) pathology
• Subject with active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, or clinically significant amyloidosis
• Inadequate organ function Subject with a history of Class III or IV congestive heart failure (CHF) or severe nonischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months prior to starting study treatment
• Ongoing treatment with chronic immunosuppressants
• Previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy
• Subject has received ASCT within 12 weeks prior to leukapheresis

Sponsors & Collaborators

• Celgene: lead

Study Sites (25)

Mayo Clinic in Arizona - Scottsdale

Scottsdale, Arizona, 85259, United States

Location

University Of California San Francisco Medical Center

San Francisco, California, 94143, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02117, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215-5450, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University Of Nebraska

Omaha, Nebraska, 68198-7680, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Mt Sinai Medical Center - NY

New York, New York, 10029, United States

Location

Columbia University Medical Center/New York-Presbyterian Hospital

New York, New York, 10032, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

University Of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center The University of Texas

Houston, Texas, 77030, United States

Location

Swedish Cancer Inst

Seattle, Washington, 98104, United States

Location

Froedtert Hospital BMT Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Local Institution - 404

Poitiers, 86021, France

Location

Local Institution - 506

Hamburg, 20246, Germany

Location

Local Institution - 505

Würzburg, 97080, Germany

Location

Local Institution - 603

Bologna, 40138, Italy

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

Local Institution - 704

Salamanca, 37007, Spain

Location

Kings College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

idecabtagene vicleucel; Lenalidomide; talquetamab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2018
• First Posted: July 26, 2018
• Study Start: December 13, 2018
• Primary Completion: January 15, 2026
• Study Completion: January 15, 2026
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

FR (1); IT (1); US (18); ES (2); DE (2); GB (1)