Safety and Efficacy of bb2121 (Ide-cel) Combinations in Multiple Myeloma (KarMMa-7)

An Exploratory Phase 1/2 Trial to Determine Recommended Phase 2 Dose (RP2D), Safety and Preliminary Efficacy of bb2121 (Ide-cel) Combinations in Subjects With Relapsed/Refractory Multiple Myeloma (KarMMa-7)

This is a global, open-label, multi-arm, multi-cohort, multi-center, phase 1/2 study to determine the safety, tolerability, efficacy, PK of bb2121 in combination with other therapies in adult subjects with R/RMM.

The following combinations will be

• Arm A will test bb2121 in combination with CC-220 (± low-dose dexamethasone)
• Arm B will test bb2121 in combination with BMS-986405 (JSMD194)

Combination agents being tested may be administered before, concurrently with and/or following (ie, maintenance) bb2121 infusion.

The study will consist of 2 parts: dose finding (Phase 1) and dose expansion (Phase 2). Dose expansion may occur in one or more arms.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: BB2121; Drug: CC-220; Drug: BMS-986405

• Study Type: Interventional
• Enrollment (Estimated): 312
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Pamplona, Spain, 31008
    • Local Institution - 201
  • Salamanca, Spain, 37007
    • Local Institution - 202
• United States
  • Alabama
    • Birmingham, Alabama, United States, 10016
      • Local Institution - 117
  • California
    • San Francisco, California, United States, 94143
      • Local Institution - 113
  • Florida
    • Jacksonville, Florida, United States, 32224-1865
      • Local Institution - 101
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Local Institution - 104
    • Atlanta, Georgia, United States, 30342
      • Local Institution - 120
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Local Institution - 114
  • Massachusetts
    • Boston, Massachusetts, United States, 02117
      • Local Institution - 108
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 124
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 109
  • New York
    • New York, New York, United States, 10016
      • New York University Langone
    • New York, New York, United States, 10032
      • Local Institution - 110
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Local Institution - 111
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Local Institution - 118
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 103
  • Texas
    • Houston, Texas, United States, 77030
      • Local Institution - 107

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

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

• Participant has documented diagnosis of MM and measurable disease, defined as:

  1. M-protein (serum protein electrophoresis [sPEP ≥ 0.5 g/dL] or urine protein electrophoresis [uPEP]): uPEP ≥ 200 mg/24 hours and/or
  2. Light chain MM without measurable disease in the serum or urine: Serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio

• Participant has received:

  1. at least 3 prior MM regimens for Arm A Cohort 1 and Arm B
  2. at least 1 but no greater than 3 prior MM regimens for Arm A Cohort 2
• Arm A Cohort 1 and Arm B: Participant has received prior treatment with an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody-containing regimen for at least 2 consecutive cycles.
• Arm A Cohort 2: Participant has received prior treatment with an immunomodulatory agent for at least 2 consecutive cycles.
• Evidence of PD during or within 6 months (measured from the last dose of any drug within the regimen) of completing treatment with the last antimyeloma regimen before study entry.
• Participant achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

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

• Participant has non-secretory MM or has history of or active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis.

• Participant has any of the following laboratory abnormalities:

  1. ANC and Platelets count as reported below
  2. Hemoglobin < 8 g/dL (< 4.9 mmol/L) (transfusion is not permitted within 21 days of screening)
  3. Creatinine clearance (CrCl) as reported below
  4. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
  5. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 ×upper limit of normal (ULN)
  6. Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for participants with documented Gilbert's syndrome
  7. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) 1.5 × ULN, or history of Grade ≥ 2 hemorrhage within 30 days, or participant requires ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors)
• Participant has inadequate pulmonary function defined as oxygen saturation (SaO2) < 92% on room air.
• Participant has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal.
• Prior exposure to CC-220 (± low-dose dexamethasone) as part of their most recent antimyeloma treatment regimen (Arm A).
• Prior exposure to BMS-986405 (JSMD194) (Arm B).
• Previous history of an allogeneic hematopoietic stem cell transplantation, treatment with any gene therapy-based therapeutic for cancer, investigational cellular therapy for cancer or BCMA targeted therapy.
• Treatment Arm A Cohort 1 and Arm B: participant has received autologous stem cell transplantation (ASCT) within 12 weeks prior to leukapheresis.
• Treatment Arm A Cohort 2: participant has received autologous stem cell transplantation (ASCT) within 12 months prior to leukapheresis.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A- bb2121 in combination with CC-220 (± low-dose dexamethasone); bb2121 will be administered at a target dose of 450 x 10^6 CAR+T cells. The combination agent will be administered at different doses and/ or schedules, depending on dose limiting toxicity (DLT) evaluation.	Biological: BB2121; CAR T Cell Therapy; Other Names: ide-cel; Drug: CC-220; Cereblon (CRBN) E3 ligase modulatory compound (CELMoD)
Experimental: Arm B- bb2121 in combination with BMS-986405 (JSMD194); bb2121 will be administered at a target dose of 450 x 10^6 CAR+T cells. The combination agent will be administered during Month 1 starting from the day of bb2121 infusion; Enrollment is closed for this Arm	Biological: BB2121; CAR T Cell Therapy; Other Names: ide-cel; Drug: BMS-986405; gamma secretase inhibitor (GSI); Other Names: JSMD194

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Does Limiting Toxicity (DLT) rates _Phase 1	Percentage of participants experiencing DLTs	Up to 28 days from start of the combination therapy
Complete Response Rate (CRR)_ Phase 2	Proportion of participants who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by investigator's review	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Event (AEs)	An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.	Up to 24 months after the last participant received any study treatment
Overall Response Rate (ORR)	Proportion of participants who achieved PR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed investigator's review	Up to 24 months after the last participant received any study treatment in the respective cohort
Progression-free Survival (PFS)	Time from first study treatment (whichever is given earlier) start date to the date of either first observation of progressive disease or death due to any cause	Up to 24 months after the last participant received any study treatment in the respective cohort
Overall Survival (OS)	Time from first study treatment (whichever is given earlier) start date to death due to any cause	Up to 24 months after the last participant received any study treatment in the respective cohort
Time to response (TTR)	Time from first study treatment start date to the first date of documented response (PR or better)	Up to 24 months after the last participant received any study treatment in the respective cohort
Duration of Response (DoR)	Time from first documentation of response (PR or better) to first documentation of PD or death due to any cause	Up to 24 months after the last participant received any study treatment in the respective cohort
Time to next antimyeloma treatment (TTNT)	Time from first study treatment (whichever is given earlier) start date to first day when participant receives another antimyeloma treatment	Up to 24 months after the last participant received any study treatment in the respective cohort
Progression-free survival after next antimyeloma therapy (PFS2)	Time from first study treatment (whichever is given earlier) start date to documentation of PD on the next-line treatment or death from any cause, whichever is first.	Up to 24 months after the last participant received any study treatment in the respective cohort
Feasibility of maintenance therapy in combination with bb2121	Cumulative incidence of the maintenance therapy starting from bb2121 infusion with death as the competing risk	Up to 4 months after bb2121 infusion in the respective cohort
Pharmacokinetics - Cmax_Phase 1 and 2	Maximum transgene level	Up to 24 months after the last participant received any study treatment in the respective cohort
Pharmacokinetics - Tmax_Phase 1 and 2	Time to maximum observed transgene level	Up to 24 months after the last participant received any study treatment in the respective cohort
Pharmacokinetics - AUC_Phase 1 and 2	Area under the curve of transgene level	Up to 24 months after the last participant received any study treatment in the respective cohort
Pharmacokinetics - AUC0-28days _Phase 1 and 2	Area under the curve of transgene level from time 0 to 28 days	Up to 24 months after the last participant received any study treatment in the respective cohort
Pharmacokinetics - Tlast _Phase 1 and 2	Time of last measurable transgene level	Up to 24 months after the last participant received any study treatment in the respective cohort

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
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Estimated): December 23, 2024
• Study Completion (Estimated): December 6, 2026

Study Registration Dates

• First Submitted: April 19, 2021
• First Submitted That Met QC Criteria: April 19, 2021
• First Posted (Actual): April 22, 2021

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Phase I; CC-220; PVd; Phase II; CAR T; Relapsed/Refractory Multiple Myeloma; BB2121; BMS-986405; ide-cel; JSMD194; DPd; KarMMa-7; DARA; POM; BTZ
• 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-007; 2020-003248-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria.

Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosurecommitment.html

• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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