Overview

A Phase 2 Study to Evaluate Safety and Efficacy of Teclistamab in Combination with Daratumumab, Lenalidomide, and Dexamethasone with or without Bortezomib as Induction Therapy and Teclistamab in Combination with Daratumumab and Lenalidomide as Maintenance Therapy in Participants with Newly Diagnosed Transplant Eligible Multiple Myeloma.

OBJECTIVES

The primary objective is to evaluate the safety and tolerability of Tec-DRd and Tec-DVRd as induction therapy and Tec-DR as post-transplant maintenance therapy in participants with ND-TEMM.

The key secondary objective is to evaluate the efficacy of Tec-DRd and Tec-DVRd as induction therapy and Tec-DR as post-transplant maintenance therapy.

Eligibility

Inclusion Criteria:

• 18 years of age to 70 years of age, inclusive
  • Have an ECOG performance status score of 0 to 2 at screening
  • Have clinical laboratory values meeting prespecified criteria during the Screening Phase.

        Participants in Arm A, A1 and Arm B must also satisfy all of the following criteria to be
        enrolled in the study:
        1. Documented multiple myeloma requiring treatment as defined by the criteria below:
          1. Multiple myeloma diagnosis according to the IMWG diagnostic criteria
          2. Measurable disease at screening as defined by any of the following:
               1. Serum M-protein level ≥1.0 g/dL or
               2. Urine M-protein level ≥200 mg/24 hours or
               3. Serum immunoglobulin free light chain level ≥10 mg/dL and abnormal serum free
                  light chain ratio
             2. Newly diagnosed participants for whom HDT and ASCT is part of the intended
             treatment plan.
             Participants Arm C and C1 must also satisfy all of the following criteria:
               1. Newly diagnosed multiple myeloma according to IMWG criteria.
               2. Must have received 4 to 6 cycles of 3 or 4 drug-induction therapy that includes a
                  proteasome inhibitor and/or an IMiD with or without anti-CD38 monoclonal antibody
                  and a single or tandem ASCT. Post-ASCT consolidation is permitted for up to 2
                  cycles as long as the total number of induction plus consolidation cycles does
                  not exceed 6.
             3 Must have received only one line of therapy and achieved at least a PR as per IMWG
             2016 without evidence of progression at the time of enrollment.
             4. Must have received HDT and ASCT within 12 months of the start of induction therapy
             and be within 6 months of the last ASCT (7 months for participants who received
             consolidation) at the time of enrollment.
             Exclusion Criteria:
             - CNS involvement or clinical signs of meningeal involvement of multiple myeloma.
               -  Stroke or seizure within 6 months prior study start Cycle1 Day1.
               -  History of transplantations requiring immunosuppressive therapy.
               -  Seropositive for HIV, HEP B, Active Hep C infection (details see protocol).
               -  COPD with a FEV1 <50% of predicted normal.
               -  Moderate /severe persistent asthma within the past 2 years or any uncontrolled
                  asthma. Exclude if FEV1 <50% of predicted normal.
               -  Concurrent medical or psychiatric condition or disease that is likely to
                  interfere with study procedures, or that in the investigators opinion would
                  constitute a hazard for participants.
               -  Contraindications or life-threatening allergies, hypersensitivity, or intolerance
                  to any study drug/excipients.
               -  Pregnant, breastfeeding, or planning to become pregnant while enrolled in this
                  study or within 6 months after the last dose of any study treatment regimen.
               -  Plans to father a child while enrolled in this study or within 3 months after the
                  last dose of any component of the study treatment regimen.
             Arm A, A1 and B
             - Prior or current systemic therapy or stem cell transplant for any plasma cell
             dyscrasia, with the exception of emergency use of a short course (equivalent of
             dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment.
             - Arm B only: Peripheral neuropathy or neuropathic pain Grade 2 or higher as defined
             by the NCI-CTCAE Version 5.
             Due to a potential interaction with bortezomib, received a strong CYP3A4 inducer
             within 5 half-lives prior to enrollment
             Arm C and C1
             - Discontinued treatment due to any AE related to lenalidomide as determined by the
             investigator.
             - Progressed on multiple myeloma therapy at any time prior to screening.
               -  Received a cumulative dose of corticosteroids equivalent to ≥40 mg of
                  dexamethasone within the 14 day period before the start of study treatment
                  administration.
               -  Intolerant to the starting dose of lenalidomide (10 mg).
             For further details on inclusion/exclusion criteria please refer to the study
             protocol.