A Study Comparing Anitocabtagene Autoleucel to Standard of Care Therapy in Participants With Relapsed/ Refractory Multiple Myeloma (iMMagine-3)

Gilead Sciences

Status and phase: Enrolling; Phase 3

Conditions: Multiple Myeloma

Treatments: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Daratumumab; Drug: Dexamethasone; Drug: Pomalidomide; Drug: Anitocabtagene Autoleucel; Drug: Carfilzomib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06413498

KT-US-679-0788

2024-511188-26 (Other Identifier)

Details and patient eligibility

About

The goal of this study (iMMagine-3) is to compare the study drug, anitocabtagene autoleucel to standard of care therapy (SOCT) in participants with relapsed/refractory multiple myeloma who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and an immunomodulatory drug.

The primary objective of this study is to compare the efficacy of anitocabtagene autoleucel versus SOCT in participants with RRMM as measured by progression-free survival (PFS) per blinded independent review committee (IRC).

Full description

After completing the treatment period, all participants who will receive anitocabtagene autoleucel, will be followed in the post-treatment follow-up period. Thereafter, participants will transition to a separate long-term follow-up study (KT-US-982-5968) to continue follow-up out to 15 years.

Enrollment: 450 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Documented historical diagnosis of multiple myeloma (MM)

• Received 1 to 3 prior lines of antimyeloma therapy, including an immunomodulatory drug (IMiD) and an anti-cluster of differentiation 38 (CD38) monoclonal antibody (mAb). A minimum of 2 consecutive cycles of an IMiD and an anti-CD38 mAb in any prior line of therapy is required. The IMiD and anti-CD38 mAb do not need to be from the same regimen in the prior line(s) of therapy.

• Documented evidence of progressive disease by IMWG criteria based on the investigator's determination on or within 12 months of the last dose of the last regimen

• Measurable disease at screening per IMWG, defined as any of the following:

  • Serum M-protein level ≥ 0.5 g/dL or urine M-protein level ≥ 200 mg/24 hours; or
  • Light chain MM without measurable disease in the serum or urine: serum free light chain ≥ 10 mg/dL and abnormal serum free light chain ratio

• Only individuals who are candidates to receive at least 1 of the 4 SOCT regimens (PVd, DPd, KDd, or Kd), as determined by the investigator, should be considered for this study

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Females of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)

Key Exclusion Criteria:

• Prior B-cell maturation antigen (BCMA)-targeted therapy
• Prior T-cell engager therapy
• Prior CAR therapy or other genetically modified T-cell therapy
• Active or prior history of central nervous system (CNS) or meningeal involvement of MM
• Cardiac atrial or cardiac ventricular MM involvement
• History of or active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis
• Active malignancy (other than MM) requiring ongoing treatment for disease control within the last 24 months. Myelodysplastic syndrome (even without ongoing treatment) is not permitted.
• Prior auto-SCT within 12 weeks before randomization
• Prior allogeneic stem cell transplant (allo-SCT)
• High-dose (eg, cumulative > 70 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 14 days before randomization
• Live vaccine ≤ 4 weeks before randomization
• Contraindication to fludarabine or cyclophosphamide
• History of allergy or hypersensitivity to any study agent or study drug components. Individuals with a history of severe hypersensitivity reaction to dimethyl sulfoxide (DMSO) are excluded.
• Life expectancy < 12 weeks

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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450 participants in 2 patient groups

Anitocabtagene Autoleucel

Experimental group

Description:

Participants with RRMM will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for 3 days followed by single dose of anitocabtagene autoleucel chimeric antigen receptor positive (CAR+) on Day 1.

Treatment:

Drug: Anitocabtagene Autoleucel

Drug: Cyclophosphamide

Drug: Fludarabine

Standard of Care Therapy (SOCT)

Active Comparator group

Description:

Participants will receive the investigator's choice of one of the following therapies: * pomalidomide, bortezomib, and dexamethasone (PVd) (21-day cycles) * daratumumab, pomalidomide, and dexamethasone (DPd) (28-day cycles) * carfilzomib, daratumumab, and dexamethasone (KDd) (28-day cycles) * carfilzomib and dexamethasone (Kd) (28-day cycles)

Treatment:

Drug: Carfilzomib

Drug: Dexamethasone

Drug: Pomalidomide

Drug: Daratumumab

Drug: Bortezomib