A Study of Different Sequences of Cilta-cel, Talquetamab in Combination With Daratumumab and Teclistamab in Combination With Daratumumab Following Induction With Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in Participants With Standard-risk Newly Diagnosed Multiple Myeloma (aMMbition)

A Phase 2, Open-label Study to Evaluate the Efficacy and Safety of Different Sequences of Ciltacabtagene Autoleucel (Cilta-cel), Talquetamab SC in Combination With Daratumumab SC (Tal-D) and Teclistamab SC in Combination With Daratumumab SC (Tec-D) Following Induction With Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) in Participants With Standard-risk Newly Diagnosed Multiple Myeloma

The purpose of this study is to evaluate the rate of response (how effectively treatment is working) with signs of potential cure at 5 years after the start of induction treatment. This is defined as a composite of sustained (at least 2 years) minimal residual disease (MRD) negativity with complete response/stringent complete response (CR/sCR) and a positron emission tomography/computed tomography (PET/CT) scan that does not show any signs of cancer at 5 years. MRD negativity and CR/sCR is defined as no detectable signs of remaining cancer cells after the treatment. This study will also characterize how well the treatments administered work in the study through progression-free survival (PFS). PFS is defined as the length of time during and after the treatment of a disease, that a participant lives with the disease, but it does not get worse.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Teclistamab; Drug: Talquetamab; Drug: Cilta-cel; Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Daratumumab

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia, 3004
    • The Alfred Hospital
  • Melbourne, Australia, 3000
    • Peter MacCallum Cancer Centre
• Brazil
  • Salvador, Brazil, 41253 190
    • Instituto D Or de Pesquisa e Ensino
  • São Paulo, Brazil, 01509 900
    • Fundacao Antonio Prudente A C Camargo Cancer Center
  • São Paulo, Brazil, 05652 900
    • Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
• Germany
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg
  • Tübingen, Germany, 72076
    • Universitaetsklinikum Tuebingen
  • Würzburg, Germany, 97080
    • Universitatsklinikum Wurzburg
• Spain
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Salamanca, Spain, 37007
    • Hosp Clinico Univ de Salamanca
  • Santander, Spain, 39008
    • Hosp. Univ. Marques de Valdecilla
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital and Clinics
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants with documented new diagnosis of multiple myeloma (MM) according to international myeloma working group (IMWG) diagnostic criteria and with no prior myeloma-directed therapy
• Participants must have standard-risk MM (stage I and II) based on revised International Staging System (R-ISS)
• Participants must be considered fit (score equals to [=] 0) or intermediate-fit (score=1) according to IMWG Frailty Index assessment (based on the Charlson Comorbidity Index, the Katz Activity of Daily Living and the Lawson Instrumental Activities of Daily Living)
• Measurable disease defined as: Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) (>=10 gram per liter [g/L] for institutions using alternative units) or urine M-protein level >= 200 milligrams per 24 hours (mg/24 hours); Light chain MM without measurable disease in the serum or the urine: Serum immunoglobulin free light chain >=10 milligrams per deciliter (mg/dL) (>=100 mg/L for institutions using alternative units) and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

Exclusion Criteria:

• Any ongoing myelodysplastic syndrome or B-cell malignancy (other than MM). Any history of malignancy, other than MM, which is considered at high risk of recurrence requiring systemic therapy
• Peripheral neuropathy or neuropathic pain of Grade >= 2, as defined by National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
• Known active or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of MM
• Stroke or seizure within 6 months of signing the informed consent form (ICF)
• Plasma cell leukemia at the time of diagnosis or any time thereafter through apheresis (>= 5 percent [%] circulating plasma cells in peripheral blood smears), Waldenstrom macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes(POEMS) syndrome, or primary amyloid light chain amyloidosis with associated organ dysfunction
• Presence of high-risk disease features: (a) Cytogenetic high risk lesions by MM fluorescence in situ hybridization (FISH) including deletion 17p (del[17p])/, t(4;14), t(14;16), amplification 1q (amp[1q21]) (>= 4 copies); (b) Presence of 1 or more extramedullary plasmacytomas
• Seropositive for human immunodeficiency virus (HIV)

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: Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel; Participants will undergo apheresis followed by 4 cycles of DVRd induction (each cycle is of 28 days) and cilta-cel will be generated from the participants' T-cells selected from the apheresis product. Upon completion of cilta-cel production, product release, and completion of induction, participants will begin consolidation with 4 cycles of Tal-D (each cycle is of 28 days), followed by a conditioning regimen (cyclophosphamide and fludarabine daily for 3 days); cilta-cel will be administered 5 to 7 days after the start of the conditioning regimen.	Drug: Talquetamab; Talquetamab will be administered subcutaneously.; Other Names: JNJ-64407564; Drug: Cilta-cel; Cilta-cel infusion will be administered intravenously.; Other Names: JNJ-68284528, Ciltacabtagene autoleucel; Drug: Bortezomib; Bortezomib will be administered subcutaneously as a part of induction.; Drug: Lenalidomide; Lenalidomide will be administered orally as a part of induction.; Drug: Dexamethasone; Dexamethasone will be administered orally as a part of induction.; Drug: Cyclophosphamide; Cyclophosphamide will be administered intravenously as a part of conditioning regimen.; Drug: Fludarabine; Fludarabine will be administered intravenously as a part of conditioning regimen.; Drug: Daratumumab; Daratumumab will be administered subcutaneously as a part of DVRd induction and Tal-D or Tec-D consolidation.; Other Names: JNJ-54767414
Experimental: Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation; Participants will undergo apheresis followed by 4 cycles of DVRd induction and Cilta-cel will be generated from the participants' T-cells selected from the apheresis product. Upon completion of cilta-cel production, product release and completion of induction, participants will begin consolidation with a conditioning regimen (cyclophosphamide and fludarabine daily for 3 days) with infusion of cilta-cel 5 to 7 days after the start of the conditioning regimen. Following cilta-cel infusion, alternating cycles of Tal-D (Cycle 1, 3, 5, and 7) and Tec-D (Cycle 2, 4, 6, and 8) will be started, no earlier than Day 84 and no later than Day 168 post cilta-cel infusion. Each cycle of Tal-D or Tec-D is 84 days which includes an extended treatment-free interval.	Drug: Teclistamab; Teclistamab will be administered subcutaneously.; Other Names: JNJ-64007957; Drug: Talquetamab; Talquetamab will be administered subcutaneously.; Other Names: JNJ-64407564; Drug: Cilta-cel; Cilta-cel infusion will be administered intravenously.; Other Names: JNJ-68284528, Ciltacabtagene autoleucel; Drug: Bortezomib; Bortezomib will be administered subcutaneously as a part of induction.; Drug: Lenalidomide; Lenalidomide will be administered orally as a part of induction.; Drug: Dexamethasone; Dexamethasone will be administered orally as a part of induction.; Drug: Cyclophosphamide; Cyclophosphamide will be administered intravenously as a part of conditioning regimen.; Drug: Fludarabine; Fludarabine will be administered intravenously as a part of conditioning regimen.; Drug: Daratumumab; Daratumumab will be administered subcutaneously as a part of DVRd induction and Tal-D or Tec-D consolidation.; Other Names: JNJ-54767414

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Response with Curative Potential	Rate of Response with curative potential is defined as the percentage of participants with a composite of durable (at least 2 years) minimal residual disease (MRD) (10^-5) negativity with complete response/stringent complete response (CR/sCR) by serology and negative positron emission tomography/computed tomography (PET/CT) imaging at 5-years after start of induction therapy. This includes: negative imaging at 5-year landmark time; MRD-negative status (at 10^-5) in 2 bone marrow examinations that are a minimum of 2 years apart; response of CR or better per the International Myeloma Working Group (IMWG) criteria; no examination showing MRD-positive status or relapse from CR in between assessments.	Up to 5 years
Progression Free Survival (PFS) Rate at 3-Year	PFS is defined as the time from the date of randomization to either progressive disease (PD), according to the IMWG response criteria, or death, whichever occurs first.	At 3-year
PFS Rate at 5-Year	PFS is defined as the time from the date of randomization to either PD, according to the IMWG response criteria, or death, whichever occurs first.	At 5-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR; Partial response [PR] or better)	ORR (PR or better) is defined as the percentage of participants with best overall response of PR or better according to IMWG response criteria.	Up to 5 years
CR or Better Rate	Rate of CR or better is defined as the percentage of participants with best overall response of CR or better according to IMWG response criteria.	Up to 5 years
Very Good Partial Response (VGPR) or Better Rate	Rate of VGPR or better is defined as the percentage of participants with best overall response of VGPR or better rate according to IMWG response criteria.	Up to 5 years
Duration of Response (DOR)	DOR is calculated among responders (with a PR or better response) from the date of initial documented response (PR or better) to the date of first documented evidence of PD as defined according to IMWG criteria or death due to any cause, whichever occurs first.	Up to 5 years
Time to First Response (TTR)	Time to response (that is, time to first response) is defined as the time between the date of randomization and the first efficacy evaluation that the participant has met all criteria for PR or better based on the computerized algorithm per IMWG criteria for those who had PR or better as their best response.	Up to 5 years
Duration of CR or Better Response	Duration of CR or better response is calculated among responders (with a CR or better response) from the date of initial documented response CR or better to the date of first documented evidence of PD as defined according to IMWG criteria or death due to any cause, whichever occurs first.	Up to 5 years
Time to First CR or Better Response	Time to first CR or better response is defined as the time between the date of randomization and the first efficacy evaluation that the participant has met all criteria for CR or better based on the computerized algorithm per IMWG criteria.	Up to 5 years
PFS on next line therapy (PFS2)	PFS2 is defined as time from randomization to progression on the next line of therapy or death, whichever comes first.	Up to 5 years
Overall Survival (OS)	OS is measured from the date of randomization to the date of death due to any cause.	Up to 5 years
MRD-negative CR Rate	MRD-negative CR is defined as the percentage of participants who achieved both CR or better and MRD negativity at a threshold of 10^-5 and 10^-6. MRD-negative CR rate will be evaluated at the first occurrence from induction treatment initiation for participants per IMWG criteria.	Up to 5 years
Number of Participants with Treatment-emergent Adverse Events (TEAEs) by Severity	An Adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment. Severity of TEAEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death related to adverse events.	Up to 5 years
Change from baseline in Health-related quality of life (HRQoL) (symptoms and functioning) using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 item instrument (EORTC-QLQ-C30)	Change from baseline in participants' HRQoL (symptoms and functioning) as assessed by EORTC-QLQ-C30 will be reported. The EORTC-QLQ-C30 includes 30 items in 5 functional scales (physical, role, emotional, cognitive, social), 1 global health status scale, 3 symptom scales (pain, fatigue, nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). The recall period is 1 week ("past week") and responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0-to-100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.	Up to 5 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2024
• Primary Completion (Estimated): September 2, 2030
• Study Completion (Estimated): September 30, 2030

Study Registration Dates

• First Submitted: August 27, 2024
• First Submitted That Met QC Criteria: August 27, 2024
• First Posted (Actual): August 29, 2024

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Carboxylic Acids; Polycyclic Compounds; Piperidines; Inorganic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Bortezomib; Dexamethasone; Cyclophosphamide; fludarabine; daratumumab; talquetamab
• Other Study ID Numbers: 54767414MMY2093 (Other Identifier: Janssen Research & Development, LLC); 2023-505792-71-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

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