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

A Phase 3, Randomized, Open-Label Study to Compare the Efficacy and Safety of Anitocabtagene Autoleucel Versus Standard of Care Therapy in Participants With Relapsed/Refractory Multiple Myeloma

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Anitocabtagene Autoleucel; Drug: Pomalidomide; Drug: Bortezomib; Drug: Dexamethasone; Drug: Daratumumab; Drug: Carfilzomib

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Medical Information; Phone Number: 844-454-5483(1-844-454-KITE); Email: medinfo@kitepharma.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anitocabtagene Autoleucel; 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.	Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously; Drug: Anitocabtagene Autoleucel; A single infusion of CAR+ transduced autologous T cells; Other Names: CART-ddBCMA
Active Comparator: Standard of Care Therapy (SOCT); 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)	Drug: Pomalidomide; Tablet administered orally; Drug: Bortezomib; Administered intravenously or subcutaneously; Drug: Dexamethasone; Tablet administered orally; Drug: Daratumumab; Administered intravenously or subcutaneously; Drug: Carfilzomib; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the time from randomization to disease progression per International Myeloma Working Group (IMWG) criteria as determined by independent review committee (IRC), or death due to any cause, whichever occurs first.	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response (CR) Rate (CR/ Stringent Complete Response (sCR))	CR rate is defined as the proportion of participants who achieved a best overall response of CR or sCR per IMWG criteria as determined by IRC.	Up to 4 years
Overall Minimal Residual Disease (MRD) Negativity	Overall MRD negativity, defined as the proportion of any MRD negativity in participants with bone marrow aspirate (< 1 in 10^5 nucleated cells per IMWG criteria using next-generation sequencing (NGS)) at any time after randomization until disease progression, subsequent anti-multiple myeloma (MM) therapy, or death.	Up to 7 years
Overall survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to 7 years
Overall Response Rate (ORR)	ORR is defined as the proportion of participants who achieve a best overall response of at least partial response (PR) or better (sCR, CR, very good partial response (VGPR), or PR) per IMWG criteria.	Up to 7 years
MRD-negative CR/sCR	MRD-negative CR/sCR is defined as the proportion of participants achieving MRD-negative CR/sCR until disease progression, subsequent anti-MM therapy, or death.	Up to 7 years
MRD-negative VGPR+	MRD-negative VGPR+ is defined as the proportion of participants achieving MRD negativity and sCR/CR/VGPR until disease progression, subsequent anti-MM therapy, or death.	Up to 7 years
Sustained MRD Negativity	Sustained MRD negativity is defined as the proportion of participants remaining MRD-negative at the 10^-5 sensitivity threshold for the specified number of months starting from the first MRD-negative assessment date to the last MRD-negative assessment date prior to disease progression, subsequent anti-MM therapy, or death. Duration may include ≥ 12 months. Sustained MRD negativity will be evaluated for overall MRD negativity, MRD-negative CR/sCR, and MRD-negative VGPR+.	Up to 7 years
Duration of Response (DOR)	DOR is derived only among participants who experience an overall response (sCR, CR, VGPR, or PR) per IMWG criteria and is defined as the time from first overall response to disease progression per IMWG criteria, or death from any cause, whichever occurs first.	Up to 7 years
Time to Progression	Time to progression is defined as the time from randomization to the first documented disease progression per IMWG criteria, or death due to disease progression, whichever occurs first.	Up to 7 years
Time to Next Treatment	Time to next treatment is defined as the time from randomization to the start of subsequent anti-MM therapy or death from any cause, whichever occurs first.	Up to 7 years
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)		First dose up to 7 years
Percentage of Participants With Anti-Anitocabtagene Autoleucel CAR Antibodies (Anitocabtagene Autoleucel Arm)		Up to 7 years
Percentage of Participants With Presence of Replication-Competent Lentivirus (Anitocabtagene Autoleucel Arm)		Up to 7 years
Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score	The EORTC-QLQ-C30 is a multi-item questionnaire measuring the following content: five (5) multi-item functional scales, three (3) multi-item symptom scales, six (6) single item symptoms scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL). Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a high level of symptoms.	Up to 7 years
Change From Baseline in the EORTC - Multiple Myeloma Module (EORTC QLQ-MY20) Score	The EORTC QLQ-MY20 has 20 items across 4 independent subscales; 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment) with a recall period of one week. Scores from each subscale are transformed from 0 to 100. For the functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening.	Up to 7 years
Change From Baseline in the European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Score	The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS). The total score for EQ-5D-5L index is presented on a range where higher scores indicate better outcome. A positive change from Baseline indicates improvement.	Up to 7 years
Percentage of Participants Using Healthcare Resources	Healthcare resource utilization will be assessed based on the numbers of hospitalizations, intensive care unit (ICU) inpatient days, and non-ICU inpatient days.	Up to 7 years

Collaborators and Investigators

• Sponsor: Kite, A Gilead Company
• Collaborators: Arcellx, Inc.
• Investigators: Study Director: Kite Study Director, Kite, A Gilead Company

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2031

Study Registration Dates

• First Submitted: May 9, 2024
• First Submitted That Met QC Criteria: May 9, 2024
• First Posted (Actual): May 14, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Myeloma; CAR-T; BCMA; ddBCMA
• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Cyclophosphamide; Pomalidomide; Daratumumab; Bortezomib; Fludarabine
• Other Study ID Numbers: KT-US-679-0788; 2024-511188-26 (Other Identifier: European Medicines Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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