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

NCT ID: NCT03601078

Last Updated: 2025-07-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 248 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-13
• Study Completion Date: 2025-10-15

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.

Detailed Description

Anti-myeloma bridging treatment is allowed for disease control while bb2121 is being manufactured for cohorts 1, 2a and 2b only. In Cohort 1b only, subjects will receive bridging therapy with 1 to 2 cycles of talquetamab, and initiate Lymphodepleting (LD) chemotherapy at least 14 days after the last dose of talquetamab.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: BB2121 in relapsed and refractory multiple myeloma participants

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

Group Type: EXPERIMENTAL

bb2121

Intervention Type: 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)

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

Group Type: EXPERIMENTAL

bb2121

Intervention Type: 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)

Talquetamab

Intervention Type: DRUG

Specified dose on specified days

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

Group Type: EXPERIMENTAL

bb2121

Intervention Type: 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)

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

Group Type: EXPERIMENTAL

bb2121

Intervention Type: 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)

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

Group Type: EXPERIMENTAL

bb2121

Intervention Type: 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)

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

Group Type: EXPERIMENTAL

bb2121

Intervention Type: 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)

Lenalomide

Intervention Type: DRUG

Specified dose on specified days

Interventions

bb2121

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)

Intervention Type: BIOLOGICAL

Lenalomide

Specified dose on specified days

Intervention Type: DRUG

Talquetamab

Specified dose on specified days

Intervention Type: DRUG

Other Intervention Names

BMS-986395; Revlimid®; TALVEY

Eligibility Criteria

Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study:

1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)

2. 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

3. 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:
• Early relapse defined as:

Cohort 2a: PD < 18 months since date of start of initial therapy. Initial therapy must contain induction, ASCT (single or tandem) and lenalidomide containing maintenance.

Cohort 2b: PD < 18 months since date of start or initial therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone Cohort 2c: Subject must have received minimum 3 cycles of induction therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone. Subjects must have had ASCT (single or tandem AND < VGPR (excluding PD) at first assessment between 70 to 110 days after last ASCT, with initial therapy without consolidation and maintenance.

Cohort 3 participants with newly diagnosed MM (NDMM) who received only induction and ASCT, without subsequent consolidation or maintenance Cohort 3

• Must have received 4 to 6 cycles of induction therapy which must contain at minimum, a proteasome inhibitor and an immunomodulatory agent and must have had single ASCT within 6 months prior to consent
• Must have achieved documented PR or VGPR at first post-ASCT assessment approximately 100 days after ASCT and this response must be maintained at screening
• Per Investigator's assessment, subject must be a candidate for single-agent lenalidomide maintenance

4. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

5. Subject must have recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy

Exclusion Criteria

The presence of any of the following will exclude a subject from enrollment:

1. Subject used any investigational agents within 14 days prior to leukapheresis or, for Cohort 3, within 14 days prior to consent

2. Subject received any of the following within the last 14 days prior to leukapheresis or, for Cohort 3, within 14 days prior to consent:

1. Plasmapheresis

2. Major surgery (as defined by the investigator)

3. Radiation therapy other than local therapy for myeloma associated bone lesions

4. Use of any systemic anti-myeloma drug therapy

3. Subject with known central nervous system involvement with myeloma

4. Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation

5. History or presence of clinically relevant central nervous system (CNS) pathology

6. Subject with active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, or clinically significant amyloidosis

7. 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

8. Ongoing treatment with chronic immunosuppressants

9. 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

10. Subject has received ASCT within 12 weeks prior to leukapheresis

11. Subject has history of primary immunodeficiency

12. Subject is positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B or active hepatitis A or C

13. Subject has uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment

14. Subject with prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years

15. Pregnant or lactating women

16. Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, and/or tocilizumab

17. Prior history of deep venous thrombosis (DVT) or pulmonary embolus (PE) within 6 months prior to consent (For Cohort 3)

18. For Cohort 1b, previous treatment with any G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D) targeted therapy or T-cell engagers

19. For Cohort 1b, known allergies, hypersensitivity, or intolerance to talquetamab or its excipients

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Mayo Clinic in Arizona - Scottsdale

Scottsdale, Arizona, United States

University Of California San Francisco Medical Center

San Francisco, California, United States

Moffitt Cancer Center

Tampa, Florida, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

University Of Nebraska

Omaha, Nebraska, United States

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Mt Sinai Medical Center - NY

New York, New York, United States

Columbia University Medical Center/New York-Presbyterian Hospital

New York, New York, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Tennessee Oncology PLLC

Nashville, Tennessee, United States

University Of Texas Southwestern Medical Center

Dallas, Texas, United States

MD Anderson Cancer Center The University of Texas

Houston, Texas, United States

Swedish Cancer Inst

Seattle, Washington, United States

Froedtert Hospital BMT Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Local Institution - 404

Poitiers, , France

Local Institution - 506

Hamburg, , Germany

Local Institution - 505

Würzburg, , Germany

Local Institution - 603

Bologna, , Italy

Clinica Universidad de Navarra

Pamplona, , Spain

Local Institution - 704

Salamanca, , Spain

Kings College Hospital NHS Foundation Trust

London, , United Kingdom

Countries

United States; France; Germany; Italy; Spain; United Kingdom

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

https://www.bmsclinicaltrials.com/us/en/clinical-trials/NCT03601078.html

BMS Clinical Trial Patient Recruiting

Other Identifiers

U1111-1216-4209

Identifier Type: OTHER

Identifier Source: secondary_id

2023-505183-10

Identifier Type: OTHER

Identifier Source: secondary_id

BB2121-MM-002

Identifier Type: -

Identifier Source: org_study_id