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

Sponsor: Janssen Research & Development, LLC

Sponsor score: 60

ClinicalTrials ID:NCT06577025

This study evaluates the efficacy of various treatment sequences in standard-risk newly diagnosed multiple myeloma. Eligible participants must have measurable disease, be fit or intermediate-fit, and have an ECOG status of 0 or 1. Exclusions include high-risk disease features and certain comorbidities. Interventions include Cilta-cel, Talquetamab, Daratumumab, Teclistamab, and others.

Patient Parameters

Program Overview

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.

Eligibility Criteria

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)

Locations

FACILITYZIPCITYSTATE
City of Hope91010DuarteCalifornia
University of California San Francisco94143San FranciscoCalifornia
University of Iowa Hospital and Clinics52242Iowa CityIowa

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