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

Celgene

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: BMS-986405; Biological: BB2121; Drug: CC-220

Study type: Interventional

Funder types: Industry

Identifiers

NCT04855136

2020-003248-10 (EudraCT Number)

BB2121-MM-007

Details and patient eligibility

About

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.

Enrollment: 312 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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312 participants in 2 patient groups

Arm A- bb2121 in combination with CC-220 (± low-dose dexamethasone)

Experimental group

Description:

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.

Treatment:

Biological: BB2121

Drug: CC-220

Arm B- bb2121 in combination with BMS-986405 (JSMD194)

Experimental group

Description:

* 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

Treatment:

Biological: BB2121

Drug: BMS-986405