An Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With High-Risk Multiple Myeloma (KarMMa-2)

A Phase 2, Multi-cohort, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With Clinical High-Risk Multiple Myeloma (KarMMa-2)

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 264 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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: bb2121; Drug: Lenalomide; Drug: Talquetamab

Detailed Description

Anti-myeloma bridging treatment is allowed for disease control while bb2121 is being manufactured for cohorts 1, 2a and 2b only.

• Study Type: Interventional
• Enrollment (Estimated): 264
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: BMS Study Connect Contact Center www.BMSStudyConnect.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com
• Study Contact Backup: Name: First line of the email MUST contain the NCT# and Site #.

Study Locations

• France
  • Poitiers, France, 86021
    • Recruiting
    • Local Institution - 404
    • Contact: Site 404
• Germany
  • Hamburg, Germany, 20246
    • Completed
    • Local Institution - 506
  • Würzburg, Germany, 97080
    • Recruiting
    • Local Institution - 505
    • Contact: Site 505
• Italy
  • Bologna, Italy, 40138
    • Completed
    • Local Institution - 603
• Spain
  • Pamplona, Spain, 31008
    • Recruiting
    • Local Institution - 703
    • Contact: Site 703
  • Salamanca, Spain, 37007
    • Recruiting
    • Local Institution - 704
    • Contact: Site 704
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • Local Institution - 801
    • Contact: Site 801
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic in Arizona - Scottsdale
      • Contact: Leif Bergsagel, Site 151
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco Medical Center
      • Contact: Alfred Chung, Site 152; Phone Number: 000-000-0000
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Contact: Melissa Alsina, Site 153; Phone Number: 813-745-6886
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University School of Medicine
      • Contact: Madhav Dhodapkar, Site 149; Phone Number: 203-785-2604
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: David Avigan, Site 159; Phone Number: 617-794-9101
    • Boston, Massachusetts, United States, 02117
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Noopur Raje, Site 146; Phone Number: 617-726-0711
    • Boston, Massachusetts, United States, 02215-5450
      • Recruiting
      • Dana Farber Cancer Institute
      • Contact: Adam Sperling, Site 145; Phone Number: 617-632-4218
    • Boston, Massachusetts, United States, 02118
      • Withdrawn
      • Local Institution - 0802
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
      • Contact: Ravi Vij, Site 156; Phone Number: 314-454-8304
  • Nebraska
    • Omaha, Nebraska, United States, 68198-7680
      • Recruiting
      • University of Nebraska
      • Contact: Christopher Dangelo, Site 155
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • John Theurer Cancer Center at Hackensack University Medical Center
      • Contact: David Siegel, Site 144; Phone Number: 551-996-8704
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center/New York-Presbyterian Hospital
      • Contact: Ran Reshef, Site 157; Phone Number: 212-342-0530
    • New York, New York, United States, 10029
      • Recruiting
      • Mt Sinai Medical Center - NY
      • Contact: Shambavi Richard, Site 154; Phone Number: 212-241-7873
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute
      • Contact: Barry Paul, Site 150; Phone Number: 980-442-2000
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Inst
      • Contact: Jesus Berdeja, Site 142; Phone Number: 615-329-0570
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
      • Contact: Larry Anderson, Site 148; Phone Number: 214-648-5906
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center The University of Texas
      • Contact: Krina Patel, Site 147; Phone Number: 713-792-6662
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Swedish Cancer Inst
      • Contact: Daniel Egan, Site 143; Phone Number: 617-699-2437
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert Hospital BMT Medical College of Wisconsin
      • Contact: Meera Mohan, Site 158; Phone Number: 414-805-4600

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Biological: 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); Other Names: BMS-986395
Experimental: Cohort 1b: BB2121 with talquetamab in relapsed and refractory multiple myeloma participants	Biological: 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); Other Names: BMS-986395; Drug: Talquetamab; Specified dose on specified days; Other Names: TALVEY
Experimental: Cohort 2a: BB2121 in multiple myeloma with Autologous stem cell transplantation participants	Biological: 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); Other Names: BMS-986395
Experimental: Cohort 2b: BB2121 in multiple myeloma without Autologous stem cell transplantation participants	Biological: 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); Other Names: BMS-986395
Experimental: Cohort 2c: BB2121 in multiple myeloma participants with inadequate response post ASCT	Biological: 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); Other Names: BMS-986395
Experimental: Cohort 3: BB2121 with lenalidomide maintenance in newly diagnosed multiple myeloma	Biological: 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); Other Names: BMS-986395; Drug: Lenalomide; Specified dose on specified days; Other Names: Revlimid®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response (CR) rate - Cohort 1	Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator	Up to approximately 5 years
Very good partial response (VGPR) rate - Cohort 2c	Percentage of subjects who achieved VGPR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator	Up to approximately 5 years
Time to response (TTR)	Time from first bb2121 infusion to first documentation of response (PR or greater) [Cohorts 1 and 2]; time from first dose of lenalidomide pre-leukapheresis to first documentation of response [Cohort 3 only]	Up to approximately 5 years
Duration of response (DoR)	Time from first documentation of response (PR or greater) to first documentation of progressive disease (PD) or death from any cause, whichever occurs first	Up to approximately 5 years
Progression-free survival (PFS)	Time from first bb2121 infusion to first documentation of PD, or death due to any cause, whichever occurs first (Cohorts 1 and 2); time from first dose of lenalidomide pre-leukapheresis to first documentation of PD, or death due to any cause, whichever occurs first (Cohort 3 only)	Up to approximately 5 years
Time to progression (TTP)	Time from first bb2121 infusion to first documentation of PD (Cohorts 1 and 2); time from first dose of lenalidomide pre-leukapheresis to first documentation of PD (Cohort 3 only)	Up to approximately 5 years
Overall survival (OS)	Time from first bb2121 infusion to time of death due to any cause (Cohorts 1 and 2); time from first dose of lenalidomide pre-leukapheresis to time of death due to any cause (Cohort 3 only)	Up to approximately 5 years
Adverse Events (AEs)	Type, frequency, seriousness and severity of adverse events (AEs), adverse events of special interest (AESIs) (including cytokine release syndrome, neurotoxicity and infection), and relationship of AE to study drug.	Up to approximately 5 years
Percentage of participants who received lenalidomide maintenance for the first 3 cycles following bb2121 infusion with at least 75% dose compliance - Cohort 3		Up to 3 months
Pharmacokinetics - Cmax	Maximum expansion of bb2121 chimeric antigen receptor (CAR) T cells	Minimum 5 years after bb2121 infusion
Pharmacokinetics - tmax	Time to peak of bb2121 CAR T cells	Minimum 5 years after bb2121 infusion
Pharmacokinetics - AUC	Area under the curve of CAR T cells	Minimum 5 years after bb2121 infusion
Pharmacokinetics - tlast	Time to last measurable CAR T cells	Minimum 5 years after bb2121 infusion
Pharmacokinetics - AUC0-28days	Area under the curve of CAR T cells from time zero to Day 28	Minimum 5 years after bb2121 infusion
Immunogenicity	Development of an anti-CAR antibody response	Minimum of 2 years after bb2121 infusion
Subject-reported outcomes as measured by European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC-QLQ-C30)	Questionnaire will be used as a measure of health-related quality of life	Minimum 5 years after bb2121 infusion
Subject-reported outcomes as measured by EuroQoL Group EQ-5D-5L Health Questionnaire	Is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal	Minimum 5 years after bb2121 infusion
Subject-reported outcomes as measured by EORTC-QLQ-MY20	Is a 20-item myeloma module intended for use among patients varying in disease stage and treatment modality	Minimum 5 years after bb2121 infusion
Overall response rate (ORR) - Cohort 1b, 2a, b, c and Cohort 3	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

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2018
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): December 30, 2030

Study Registration Dates

• First Submitted: July 17, 2018
• First Submitted That Met QC Criteria: July 17, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Open-label; Phase 2; Relapsed and Refractory Multiple Myeloma; bb2121; High Risk Multiple Myeloma; Multi-cohort
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Idecabtagene vicleucel
• Other Study ID Numbers: BB2121-MM-002; U1111-1216-4209 (Other Identifier: WHO); 2018-000264-28 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No