A Phase 1b Dose Escalation Study of the Combination of the Bispecific T Cell Redirection Antibodies Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (RedirecTT-1)

  • STATUS
    Recruiting
  • End date
    May 28, 2024
  • participants needed
    102
  • sponsor
    Janssen Research & Development, LLC
Updated on 25 October 2022
lenalidomide
human chorionic gonadotropin
bortezomib
carfilzomib
refractory multiple myeloma

Summary

The purpose of this study is to identify the recommended Phase 2 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). The RP2R(s) will describe the combination doses and schedules of (tal+tec+dara) the treatment combinations to be pursued in Phase 2.

Description

Multiple myeloma is a malignant plasma cell disorder characterized by production of monoclonal proteins (M proteins), which are comprised of pathologic immunoglobulins (Ig) or fragments of such, which have subsequently lost their normal function. Talquetamab is a humanized IgG4PAA bispecific antibody designed to target G protein-coupled receptor family C group 5-member D (GPRC5D) and the CD3 molecule found on T lymphocytes (T cell). Teclistamab is a humanized IgG4PAA bispecific antibody designed to target B cell maturation antigen (BCMA) and the CD3 molecule found on T cells. Daratumumab is a human IgG1ĸ monoclonal antibody that binds with high affinity to a unique epitope on cluster of differentiation 38 (CD38) in a variety of hematological malignancies including multiple myeloma. Rationale for combining talquetamab and teclistamab is that, these agents promote the activation of T cells and induce myeloma cell lysis mediated by secreted perforin and various granzymes stored in the secretory vesicles of cytotoxic T cells and daratumumab induces lysis of CD38-expressing tumor cells by a number of mechanisms, including complement-dependent cytotoxicity (CDC), antibody dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), through activation of complement proteins, natural killer (NK) cells, and macrophages, respectively. 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.

Details
Condition Multiple Myeloma
Treatment Daratumumab, Talquetamab, Teclistamab
Clinical Study IdentifierNCT04586426
SponsorJanssen Research & Development, LLC
Last Modified on25 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria based on documented medical history
Participant could not tolerate or has disease that is relapsed or refractory to established therapies, including the last line of therapy (except as noted in point 'a' and 'b'). (a) For cohorts without daratumumab, prior lines of therapy must include a proteasome inhibitor (PI) (example, bortezomib, carfilzomib, ixazomib), an immunomodulatory drug (IMiD) (example, thalidomide, lenalidomide, pomalidomide), and an anti-CD38 therapy (example, daratumumab, isatuximab) in any order. (b) For cohorts with daratumumab, prior lines of therapy must include a PI (example, bortezomib, carfilzomib, ixazomib) and an IMiD (example, thalidomide, lenalidomide, pomalidomide). Treatment with an anti-CD38 therapy (example, daratumumab) is allowed greater than equal to (>=) 90 days prior to study treatment if the participant did not discontinue prior treatment due to adverse events related to anti-CD38 therapy
Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at screening and immediately before the start of study drug administration
Women of childbearing potential must have a negative highly-sensitive serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test (less than [<] 5 international units per milliliter [IU/mL]) at screening and a negative urine or serum pregnancy test within 24 hours prior to the first step-up dose and the first dose of each treatment cycle
Men must agree not to donate sperm for reproduction during the study and for a minimum 100 days after receiving the last dose of study treatment

Exclusion Criteria

Prior anticancer therapy as follows: a) 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; b) monoclonal antibody treatment for multiple myeloma within 21 days; c) cytotoxic therapy within 21 days; d) proteasome inhibitor (PI) therapy within 14 days; e) immunomodulatory drug (IMiD) therapy within 7 days; f) radiotherapy within 21 days. However, if the radiation portal covered less than or equal to (<=) of the bone marrow reserve, the participant is eligible irrespective of the end date of radiotherapy; g) gene modified adoptive cell therapy (example, chimeric antigen receptor modified T cells, natural killer [NK] cells) within 3 months
A cumulative dose of corticosteroids equivalent to more than or equal to (>=) 140 milligram (mg) of prednisone within 14 days
Live, attenuated vaccine within 4 weeks prior to first dose of study drug unless approved by sponsor
Active hepatitis C infection as measured by positive hepatitis C virus (HCV)-RNA testing. Participants with a history of HCV antibody positivity must undergo HCV RNA testing
Known allergies, hypersensitivity, or intolerance to daratumumab, talquetamab, teclistamab, or their excipients
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