A Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma

Study Overview
=================
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.

Official Title
-----------------
A Multi-arm Phase 1b Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma

Conditions
-----------------
Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: Teclistamab
* Drug: Daratumumab
* Drug: Pomalidomide
* Drug: Lenalidomide
* Drug: Bortezomib
* Drug: Nirogacestat


Participation Criteria
=================
Eligibility Criteria
-----------------
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 100 days 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Regimen A: Teclistamab + Daratumumab + Pomalidomide<br>Participants will receive teclistamab plus daratumumab plus pomalidomide. | Drug: Teclistamab<br>* Participants will receive teclistamab.<br>* Other names: JNJ-64007957;Drug: Daratumumab<br>* Participants will receive daratumumab.<br>Drug: Pomalidomide<br>* Participants will receive pomalidomide.<br>|
| Experimental: Treatment Regimen B: Teclistamab + Daratumumab + Lenalidomide + Bortezomib (21-day Cycles)<br>Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 21-day cycles. | Drug: Teclistamab<br>* Participants will receive teclistamab.<br>* Other names: JNJ-64007957;Drug: Daratumumab<br>* Participants will receive daratumumab.<br>Drug: Lenalidomide<br>* Participants will receive lenalidomide.<br>Drug: Bortezomib<br>* Participants will receive bortezomib.<br>|
| Experimental: Treatment Regimen C: Teclistamab + Nirogacestat<br>Participants will receive teclistamab plus nirogacestat. | Drug: Teclistamab<br>* Participants will receive teclistamab.<br>* Other names: JNJ-64007957;Drug: Nirogacestat<br>* Participants will receive nirogacestat.<br>|
| Experimental: Treatment Regimen D: Teclistamab + Lenalidomide<br>Participants will receive teclistamab plus lenalidomide. | Drug: Teclistamab<br>* Participants will receive teclistamab.<br>* Other names: JNJ-64007957;Drug: Lenalidomide<br>* Participants will receive lenalidomide.<br>|
| Experimental: Treatment Regimen E: Teclistamab + Daratumumab + Lenalidomide<br>Participants will receive teclistamab plus daratumumab plus lenalidomide. | Drug: Teclistamab<br>* Participants will receive teclistamab.<br>* Other names: JNJ-64007957;Drug: Daratumumab<br>* Participants will receive daratumumab.<br>Drug: Lenalidomide<br>* Participants will receive lenalidomide.<br>|
| Experimental: Treatment Regimen F: Teclistamab + Daratumumab + Lenalidomide + Bortezomib (28-day Cycles)<br>Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 28-day cycles. | Drug: Teclistamab<br>* Participants will receive teclistamab.<br>* Other names: JNJ-64007957;Drug: Daratumumab<br>* Participants will receive daratumumab.<br>Drug: Lenalidomide<br>* Participants will receive lenalidomide.<br>Drug: Bortezomib<br>* Participants will receive bortezomib.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Incidence of Adverse Events (AEs) | 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. | Up to 2 year and 5 months | 
| Number of Participants with AEs by Severity | Number of participants with AEs by severity will be reported. | Up to 2 year and 5 months | 
| Number of Participants with Abnormalities in Laboratory Values | Number of participants with abnormalities in laboratory values (such as serum chemistry, hematology) will be reported. | Up to 2 year and 5 months | 
| Number of Participants with Dose-Limiting Toxicity (DLT) | 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. | Up to Cycle 2 Day 21 (each cycle is of 28 days for Treatment Regimen A and 21 days for Treatment Regimen B) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | 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. | Up to 2 year and 5 months | 
| Very Good Partial Response (VGPR) or Better Response Rate | 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. | Up to 2 year and 5 months | 
| Complete Response (CR) or Better Response Rate | 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. | Up to 2 year and 5 months | 
| Stringent Complete Response (sCR) Rate | sCR rate is defined as the proportion of participants who achieve an sCR according to the IMWG 2016 criteria. | Up to 2 year and 5 months | 
| Duration of Response | 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. | Up to 2 year and 5 months | 
| Time to Response | 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. | Up to 2 year and 5 months | 
| Serum Concentrations of Teclistamab | Serum concentrations of teclistamab will be reported. | Up to 2 year and 5 months | 
| Serum Concentrations of Daratumumab | Serum concentrations of daratumumab will be reported. | Up to 2 year and 5 months | 
| Serum Concentrations of Nirogacestat | Serum concentration of nirogacestat will be reported. | Up to 2 year and 5 months | 
| Number of Participants with Presence of Anti-Drug Antibodies to Teclistamab | Number of participants with anti-drug antibodies to teclistamab will be reported for all treatment regimens. | Up to 2 year and 5 months | 
| Number of Participants with Presence of Anti-Drug Antibodies to Daratumumab | Number of participants with anti-drug antibodies to daratumumab will be reported for Treatment Regimen A, B, E and F. | Up to 2 year and 5 months | 
| Number of Participants with Presence of Anti-Drug Antibodies to Recombinant Human Hyaluronidase PH20 Enzyme (rHuPH20) | Number of participants with anti-drug antibodies to rHuPH20 will be reported for Treatment Regimen A, B, E and F. | Up to 2 year and 5 months |