Clinical trial NCT06413498: A Study Comparing Anitocabtagene Autoleucel to Standard of Care Therapy in Participants With Relapsed/ Refractory Multiple Myeloma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
CAR-T
ddBCMA
BCMA
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: Arcellx, Inc.
First posted: 2024-05-14
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility 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.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to 4 years
Secondary outcomes:
measure: Complete Response (CR) Rate (CR/ Stringent Complete Response (sCR))
timeFrame: Up to 4 years
measure: Overall Minimal Residual Disease (MRD) Negativity
timeFrame: Up to 7 years
measure: Overall survival (OS)
timeFrame: Up to 7 years
measure: Overall Response Rate (ORR)
timeFrame: Up to 7 years
measure: MRD-negative CR/sCR
timeFrame: Up to 7 years
measure: MRD-negative VGPR+
timeFrame: Up to 7 years
measure: Sustained MRD Negativity
timeFrame: Up to 7 years
measure: Duration of Response (DOR)
timeFrame: Up to 7 years
measure: Time to Progression
timeFrame: Up to 7 years
measure: Time to Next Treatment
timeFrame: Up to 7 years
measure: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: First dose up to 7 years
measure: Percentage of Participants With Anti-Anitocabtagene Autoleucel CAR Antibodies (Anitocabtagene Autoleucel Arm)
timeFrame: Up to 7 years
measure: Percentage of Participants With Presence of Replication-Competent Lentivirus (Anitocabtagene Autoleucel Arm)
timeFrame: Up to 7 years
measure: Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
timeFrame: Up to 7 years
measure: Change From Baseline in the EORTC - Multiple Myeloma Module (EORTC QLQ-MY20) Score
timeFrame: Up to 7 years
measure: Change From Baseline in the European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Score
timeFrame: Up to 7 years
measure: Percentage of Participants Using Healthcare Resources
timeFrame: Up to 7 years
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Santa Monica
country: United States
facility: UCLA Department of Medicine-Hematology/Oncology
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Indianapolis
country: United States
facility: IU Melvin and Bren Simon Comprehensive Cancer Center
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute, St. Matthews Campus
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Corewell Health - Lemmen-Holton Cancer Pavilion
state: Michigan
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: Charlotte
country: United States
facility: Novant Health Cancer Institute Hematology
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Memphis
country: United States
facility: Baptist Cancer Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Richmond
country: Australia
facility: Epworth HealthCare
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH Elisabethinen, Hamatologie mit Stammzelltransplantation, Hamostaseologie und medizinische Onkologie
city: St. Poelten
country: Austria
facility: University Hospital St. Poelten, Department of Internal Medicine I
city: Flemish Brabant
country: Belgium
facility: UZ Leuven
city: Gent Oost-Vlaanderen
country: Belgium
facility: UZ Gent
city: Lille
country: France
facility: CHU de Lille- Hopital Claude Huriez
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: CHU De Montpellier - Hopital Saint Eloi
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Hopital Saint Antoine
city: Pierre-Benite
country: France
facility: Hôpital Lyon Sud
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers
city: Rennes
country: France
facility: CHU de Rennes
city: Toulouse
country: France
facility: CHU de Toulouse. IUCT Oncopole
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
state: MI
city: Bologna
country: Italy
facility: IRCCS AOU di Bologna
city: Hyogo
country: Japan
facility: Hyogo Medical University Hospital
city: Tokyo
country: Japan
facility: Japanese Red Cross Medical Center
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: El Palmar
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust, Bristol Haematology and Oncology Centre
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust, St James's University Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: Newcastle
country: United Kingdom
facility: Newcastle Hospitals NHS Foundation Trust, Freeman Hospital
Study officials:
affiliation: Kite, A Gilead Company
name: Kite Study Director
role: STUDY_DIRECTOR
References: