A Phase 1b/2 Dose Escalation and Expansion Study of the Combination of the Bispecific T Cell Redirection Antibodies Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma

Study Identifier:
64007957MMY1003
CT.gov Identifier:
NCT04586426
EudraCT Identifier:
2019-004124-38
EU Trial (CTIS) Number:
2023-503439-16-00
Study Contact Information:
(210) 593-5651 or [email protected]
Study Complete

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Study Summary

To identify the recommended phase II regimen(s) (RP2R[s]) and schedule for the study treatment (Part 1) and to characterize the safety of the RP2R(s) for the study treatment (Part 2). Responses were investigator assessed. AEs were graded per CTCAE v5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT criteria.

To report efficacy and ongoing safety from phase 1b of RedirecTT-1 at an extended mFU of 36.2 mo.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Multiple Myeloma
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Part 1: Dose Escalation Participants will receive tec+tal with or without daratumumab in 28-day cycles following initial step-up doses. Drug: Talquetamab Talquetamab will be administered by subcutaneous (SC) injection. Drug: Teclistamab Teclistamab will be administered by SC injection. Drug: Daratumumab Daratumumab will be administered by SC injection. Experimental: Part 2: Dose Expansion Participants will receive treatment doses (combination of tal+tec and dara+tal+tec regimens) which will be determined by the recommended Phase 2 regimen (s) (RP2R[s]) of the study treatment identified in Part 1. Drug: Talquetamab Talquetamab will be administered by subcutaneous (SC) injection. Drug: Teclistamab Teclistamab will be administered by SC injection. Drug: Daratumumab Daratumumab will be administered by SC injection. Experimental: Part 3: Phase 2 Participants will receive teclistamab + talquetamab combination therapy, at the RP2R selected from Part 1 and Part 2. Drug: Talquetamab Talquetamab will be administered by subcutaneous (SC) injection. Drug: Teclistamab Teclistamab will be administered by SC injection. This study consists 3 periods: screening phase (up to 28 days), treatment phase (start of study drug administration and continues until the completion of the end of treatment [EOT] visit); and a post-treatment follow-up phase (after end of treatment and up to 16 weeks after last dose of study drug(s) for each participant). End of study is defined as last study assessment for last participant in study. Total duration of study is up to 1 year and 6 months. Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed at specified time points during this study. Participants safety and study conduct will be monitored throughout the study. Patients had been treated with the recommended phase 2 regimen (RP2R) of 0.8 mg/kg of TALVEY in combination with 3 mg/kg of TECVAYLI every other week, Pubmed: ...Five dose levels of talquetamab plus teclistamab were investigated: talquetamab at 0.2 mg per kilogram plus teclistamab at 0.75 mg per kilogram weekly (dose level 1), talquetamab at 0.2 mg per kilogram plus teclistamab at 1.5 mg per kilogram weekly (dose level 2), talquetamab at 0.4 mg per kilogram plus teclistamab at 1.5 mg per kilogram weekly (dose level 3), talquetamab at 0.8 mg per kilogram plus teclistamab at 1.5 mg per kilogram every 2 weeks (dose level 4), and talquetamab at 0.8 mg per kilogram plus teclistamab at 3.0 mg per kilogram every 2 weeks (dose level 5). Dose level 5 was selected as the recommended phase 2 regimen. Step-up doses were adapted from schedules used with each monotherapy to mitigate severe cytokine release syndrome and were administered 2 to 4 days apart and before full treatment doses... EHA 2025: Pts received Tal 0.8 mg/kg Q2W + Tec 3.0 mg/kg Q2W, with step-up doses; pts could switch to Q4W dosing at investigator’s discretion after cycle 6 or after cycle 4 with confirmed ≥VGPR.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Study Complete

    Requirements information
    Inclusion criteria
    • Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria Part 1 and 2: Participant could not tolerate or has disease that is relapsed or refractory to established therapies, including the last line of therapy. Part 3: (a) Relapsed or refractory disease, and exposed to a PI, IMiD, and an anti-CD38 mAb; (b) Documented evidence of progressive disease based on investigator's determination of response by IMWG criteria on or after their last regimen Part 1 and Part 2: Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at screening and immediately before the start of study drug administration. Part 3: ECOG performance status grade of 0, 1, or 2 at screening and immediately before the start of study drug administration
    • Nonsecretory/oligosecretory disease was permitted. Prior CAR-T and non-BCMA/-GPRC5D BsAb therapies were permitted.
    Exclusion criteria
    • All Parts: Targeted therapy, epigenetic therapy, or treatment with an investigational treatment or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less. Part 3: prior BCMA targeted bispecific antibody therapy; prior GPRC5D targeted therapy
    • All Parts: Allogeneic stem cell transplant within 6 months before the first dose of study treatment.
    • All Parts: Central nervous system involvement or clinical signs of meningeal involvement of multiple myeloma.
    • All Parts: Active plasma cell leukemia (greater than [>]2.0*10^9/L plasma cells by standard differential), Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M- protein, and skin changes), or primary amyloid light chain amyloidosis

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Daniel Morillo Giles
    Status
    Recruiting
    Condition(s) Treated at Site
    Multiple Myeloma