Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion

Description

Summary

The purpose of this study is to identify recommended Phase 2 doses (RP2Ds) and schedules for each combination (combination 1: daratumumab and JNJ-64407564 [anti-GPRC5DxCD3] or combination 2: daratumumab and JNJ-64007957 [anti-BCMAxCD3]) and to characterize the safety of each RP2D for each combination.

Official Title

A Phase 1b Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Subjects With Multiple Myeloma

Details

Multiple myeloma is a malignant plasma cell disorder characterized by osteolytic lesions, increased susceptibility to infections, hypercalcemia, and renal failure. Overall rationale of study is that daratumumab in combination with JNJ-64407564 [anti-GPRC5DxCD3] or JNJ-64007957 [anti-BCMAxCD3] may lead to enhanced clinical responses in treatment of relapsed or refractory multiple myeloma through multiple mechanisms of action. Daratumumab is human immunoglobulin G1 kappa monoclonal antibody (IgG1k) that binds with high affinity to a unique epitope on cluster of differentiation 38 (CD38) in a variety of hematological malignancies including multiple myeloma. JNJ-64407564 (anti-GPRC5DxCD3) and JNJ-64007957 (anti-BCMAxCD3) are bispecific T cell redirection antibodies. JNJ-64407564 (anti-GPRC5DxCD3) binds to cluster of differentiation 3 (CD3) receptor complex on T cells and to G protein-coupled receptor family C group 5-member D (GPRC5D), a 7‑transmembrane receptor protein on plasma cells and JNJ-64007957 (anti-BCMAxCD3) binds to human and cynomolgus-CD3 and B cell maturation antigen (BCMA). Purpose of study is to evaluate safety of daratumumab in combination with bispecific T cell redirecting antibodies, and to evaluate antitumor activity of each combination. Study consists of a screening period, treatment period (Part 1: dose escalation and Part 2: dose expansion) and a post treatment follow-up period (after end of treatment and up to 16 weeks after last dose. End of study is defined as last study assessment for last participant in study. Total duration of study is approximately 2.4 years. Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed at specified time points. Participants safety will be monitored throughout study by Study Evaluation Team (SET). SET consists of members of sponsor's study team and participating investigators.

Keywords

Multiple Myeloma Neoplasms, Plasma Cell Daratumumab Antibodies Antibodies, Monoclonal JNJ-64407564 JNJ-64007957

Eligibility

You can join if…

Open to people ages 18 years and up

  • Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
  • Must have either of the following: a) received at least 3 prior lines of therapy including a proteasome inhibitor (PI) (greater than or equal to [>=] 2 cycles or 2 months of treatment) and an immunomodulatory drug (IMiD) (>=2 cycles or 2 months of treatment) in any order during the treatment or b) disease that is double refractory to a PI and an IMiD
  • Measurable disease at Screening as defined by any of the following: Serum M-protein level >= 1.0 grams per deciliter (g/dL) (in non- immunoglobulin G (IgG) myeloma, an M-protein level >=0.5 g/dL); or Urine M-protein level >=200 milligram (mg)/24 hours; or Light chain multiple myeloma: Serum immunoglobulin free light chain >=10 milligrams per deciliter (mg/dL) and abnormal serum immunoglobulin kappa lambda free light chain ratio
  • Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at screening and at Cycle 1, Day 1 predose
  • Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (Beta- human chorionic gonadotropin [Beta-hCG]) or urine

You CAN'T join if...

  • Treatment in the prior 3 months with an anti- cluster of differentiation 38 (CD38) therapy (example, daratumumab), or discontinuation of a prior anti-CD38 therapy at any time due to an adverse event related to the anti-CD38 therapy
  • Live, attenuated vaccine within 4 weeks prior to the first dose of study drug
  • Central nervous system involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, whole body magnetic resonance imaging (MRI) and lumbar cytology are required
  • Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded
  • Seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)

Locations

  • University of California, San Francisco not yet accepting patients
    San Francisco California 94143 United States
  • City of Hope National Medical Center not yet accepting patients
    Duarte California 91010 United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
Janssen Research & Development, LLC
ID
NCT04108195
Phase
Phase 1
Study Type
Interventional
Last Updated