Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to characterize the safety and tolerability of teclistamab when administered in different combination regimen and to identify the optimal dose(s) of teclistamab combination regimens.
Interventions
DRUGTeclistamab
Participants will receive teclistamab.
DRUGDaratumumab
Participants will receive daratumumab.
DRUGPomalidomide
Participants will receive pomalidomide.
DRUGLenalidomide
Participants will receive lenalidomide.
DRUGBortezomib
Participants will receive bortezomib.
DRUGNirogacestat
Participants will receive nirogacestat.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have documented initial diagnosis of multiple myeloma according to international myeloma working group (IMWG) diagnostic criteria * Meet treatment regimen-specific requirements as follows: Treatment Regimen A (teclistamab \[tec\]-daratumumab \[dara\]-pomalidomide \[pom\]) only: Participant has relapsed or refractory multiple myeloma and has received 1 to 3 prior lines of therapy, including exposure to a proteasome inhibitor (PI) and lenalidomide; Treatment Regimen B (tec-dara-lenalidomide \[len\]-bortezomib \[bor\]) only: Participant has newly diagnosed or relapsed/refractory multiple myeloma and is naive to treatment with lenalidomide; Treatment Regimen C (tec-nirogacestat \[niro\]) only: Participant has relapsed or refractory multiple myeloma and has 1) received 3 or more prior lines of therapy or 2) is double refractory to a PI and an immunomodulatory drug (IMiD) and triple exposed to a PI, an IMiD, and an anti-cluster of differentiation (CD)38 monoclonal antibody (mAb); Treatment Regimen D (tec-len) only: Participant has multiple myeloma and has received greater than or equal to (\>=) 2 prior lines of therapy, including exposure to a PI, an IMiD, and an anti-CD38 mAb; Treatment Regimen E (tec-dara-len) only: Participant has newly diagnosed multiple myeloma or if previously treated has received 1 to 3 prior lines of therapy, including exposure to a PI and an IMiD; Treatment Regimen F (tec-dara-len-bor) only: Participant has newly diagnosed multiple myeloma * Have measurable disease at screening as defined by at least one of the following: serum M-protein level \>= 1.0 gram/deciliter (g/dL); or urine M-protein level \>= 200 milligrams (mg)/24 hours; or light chain multiple myeloma: serum immunoglobulin (Ig) free light chain (FLC) \>= 10 milligram/deciliter (mg/dL) and abnormal serum Ig kappa lambda FLC ratio * A woman of childbearing potential must have a negative serum (beta human chorionic gonadotropin \[hCG\]) pregnancy test at screening and a negative urine or serum pregnancy test within 24 hours before the start of study treatment administration and must agree to further serum or urine pregnancy tests during the study * A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 6 months after the last dose of study treatment
Exclusion criteria
* Prior treatment with any therapy that targets B-cell maturation antigen (BCMA): This exclusion does not apply to Treatment Regimen C * Live, attenuated vaccine within 30 days before the first dose of study treatment * Received a cumulative dose of corticosteroids equivalent to \>= 140 mg of prednisone within the 14-day period before the start of study treatment administration * Active central nervous system (CNS) involvement or exhibition of clinical signs of meningeal involvement of multiple myeloma. If either is suspected, brain magnetic resonance imaging (MRI) and lumbar cytology are required * Known to be seropositive for human immunodeficiency virus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Incidence of Adverse Events (AEs) | Up to 2 year and 5 months | An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. |
| Number of Participants with AEs by Severity | Up to 2 year and 5 months | Number of participants with AEs by severity will be reported. |
| Number of Participants with Abnormalities in Laboratory Values | Up to 2 year and 5 months | Number of participants with abnormalities in laboratory values (such as serum chemistry, hematology) will be reported. |
| Number of Participants with Dose-Limiting Toxicity (DLT) | Up to Cycle 2 Day 21 (each cycle is of 28 days for Treatment Regimen A and 21 days for Treatment Regimen B) | The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and defined as any of the following events: hematological / non hematological toxicity of Grade 3 or higher. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to 2 year and 5 months | ORR is defined as the proportion of participants who achieve partial response (PR) or better according to the international myeloma working group (IMWG) 2016 criteria. |
| Very Good Partial Response (VGPR) or Better Response Rate | Up to 2 year and 5 months | VGPR or better response rate is defined as the proportion of participants who achieve a VGPR or better response (stringent complete response \[sCR\]+ complete response \[CR\]+VGPR) according to the IMWG 2016 criteria. |
| Complete Response (CR) or Better Response Rate | Up to 2 year and 5 months | CR or better response rate is defined as the proportion of participants who achieve a CR or better response (sCR+CR) according to the IMWG 2016 criteria. |
| Stringent Complete Response (sCR) Rate | Up to 2 year and 5 months | sCR rate is defined as the proportion of participants who achieve an sCR according to the IMWG 2016 criteria. |
| Duration of Response | Up to 2 year and 5 months | Duration of response is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of progressive disease (PD), per IMWG criteria. |
| Time to Response | Up to 2 year and 5 months | Time to response is defined as the time between date of first dose of study treatment and the first efficacy evaluation at which the participant has met all criteria for PR or better. |
| Serum Concentrations of Teclistamab | Up to 2 year and 5 months | Serum concentrations of teclistamab will be reported. |
| Serum Concentrations of Daratumumab | Up to 2 year and 5 months | Serum concentrations of daratumumab will be reported. |
| Serum Concentrations of Nirogacestat | Up to 2 year and 5 months | Serum concentration of nirogacestat will be reported. |
| Number of Participants with Presence of Anti-Drug Antibodies to Teclistamab | Up to 2 year and 5 months | Number of participants with anti-drug antibodies to teclistamab will be reported for all treatment regimens. |
| Number of Participants with Presence of Anti-Drug Antibodies to Daratumumab | Up to 2 year and 5 months | Number of participants with anti-drug antibodies to daratumumab will be reported for Treatment Regimen A, B, E and F. |
| Number of Participants with Presence of Anti-Drug Antibodies to Recombinant Human Hyaluronidase PH20 Enzyme (rHuPH20) | Up to 2 year and 5 months | Number of participants with anti-drug antibodies to rHuPH20 will be reported for Treatment Regimen A, B, E and F. |
Countries
Australia, Belgium, France, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research and Development, LLC Clinical Trial
Janssen Research and Development LLC
Outcome results
None listed