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A Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Participants With Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Daratumumab
Talquetamab
Teclistamab
Pomalidomide
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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 monoclonal protein (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 (Ig) free light chain (FLC) >=10 milligrams per deciliter (mg/dL) and abnormal serum Ig kappa lambda FLC 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 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 1 day before the first dose of study drug

Exclusion Criteria:

  • 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 unless approved by sponsor
  • Active Central nervous system involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, brain 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
  • Active hepatitis C infection as measured by positive hepatitis C virus- ribonucleotide (HCV)-RNA testing. Participants with a history of Hepatitis C virus antibody positivity must undergo HCV-RNA testing

Sites / Locations

  • City of Hope National Medical Center
  • University of California, San Francisco
  • Mount Sinai Medical Center
  • Levine Cancer Institute
  • Wake Forest Baptist Medical Center
  • University of Pennsylvania
  • Vanderbilt - Ingram Cancer Center
  • Medical College Of Wisconsin
  • Tom Baker Cancer Centre
  • University Health Network (UHN) Princess Margaret Cancer Centre
  • Universitatsklinikum Freiburg
  • Universitaetsklinikum Hamburg Eppendorf
  • Universitaetsklinikum Heidelberg
  • Universitätsklinikum Würzburg
  • VU Medisch Centrum
  • LUMC
  • Hosp. Clinic I Provincial de Barcelona
  • Inst. Cat. Doncologia-H Duran I Reynals
  • Germans Trias I Pujol
  • Hosp. Univ. Fund. Jimenez Diaz
  • Clinica Univ. de Navarra
  • Hosp. Clinico Univ. de Salamanca

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part 1: Dose Escalation

Part 2: Dose Expansion

Arm Description

Participants will be assigned to either a combination of 1) daratumumab plus teclistamab or 2) daratumumab plus talquetamab or 3) daratumumab plus talquetamab plus pomalidomide or 4) daratumumab plus teclistamab plus pomalidomide.

Participants will be treated with the RP2D(s) for selected treatment combinations determined in Part 1.

Outcomes

Primary Outcome Measures

Part 1: Number of Participants With Dose Limiting Toxicity (DLT)
The dose limiting toxicities are based on drug related adverse events and defined as any of the following events: hematological or non-hematological toxicity of grade 3 or higher.
Part 1: Number of Participants With Dose Limiting Toxicity by Severity
The dose limiting toxicities are based on drug related adverse events and defined as any of the following events: hematological or non-hematological toxicity of grade 3 or higher.
Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product.
Part 2: Number of Participants With Adverse Events and SAEs by Severity
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product.

Secondary Outcome Measures

Serum Concentration of Daratumumab
Serum concentration of daratumumab will be assessed.
Serum Concentration of Talquetamab
Serum concentration of talquetamab will be assessed.
Serum Concentration of Teclistamab
Serum concentration of teclistamab will be assessed.
Biomarker Assessment of Daratumumab
Serum cytokine concentrations will be measured at the time of drug infusion of daratumumab for biomarker assessment.
Biomarker Assessment of Talquetamab
Serum cytokine concentrations will be measured at the time of drug infusion of talquetamab for biomarker assessment.
Biomarker Assessment of Teclistamab
Serum cytokine concentrations will be measured at the time of drug infusion of teclistamab for biomarker assessment.
Number of Participants With Anti-Drug Antibodies to Daratumumab
Number of participants with anti-drug antibodies to daratumumab will be assessed.
Number of Participants With Anti-Drug Antibodies to Talquetamab
Number of participants with anti-drug antibodies to talquetamab will be assessed.
Number of Participants With Anti-Drug Antibodies to Teclistamab
Number of Participants with anti-drug antibodies to teclistamab will be assessed.
Overall Response Rate (ORR)
ORR is defined as the percentage of participants who have a partial response (PR) or better according to the International Myeloma Working Group (IMWG) criteria.
Clinical Benefit Rate
Clinical benefit rate (ORR + minimal response [MR]) is defined as the of participants who have a MR or better according to the IMWG criteria.
Duration of Response (DOR)
DOR is defined as the time from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria.
Time to Response
Time to response is defined as the time between date of first dose of study drug and the first efficacy evaluation that the participant has met all criteria for PR or better.

Full Information

First Posted
September 26, 2019
Last Updated
October 10, 2023
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT04108195
Brief Title
A Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Participants With Multiple Myeloma
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 21, 2020 (Actual)
Primary Completion Date
September 9, 2024 (Anticipated)
Study Completion Date
September 9, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to identify recommended Phase 2 doses (RP2Ds) for each treatment combination (between daratumumab plus talquetamab and teclistamab plus daratumumab with or without pomalidomide) and to characterize the safety of each RP2D for selected treatment combinations.
Detailed Description
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 talquetamab or teclistamab 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. Talquetamab and teclistamab are bispecific T cell redirection antibodies. Talquetamab 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 teclistamab binds to human and cynomolgus-CD3 and B cell maturation antigen (BCMA). Purpose of study is to evaluate safety of daratumumab, with or without pomalidomide, in combination with talquetamab and teclistamab, and to evaluate preliminary 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
291 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Dose Escalation
Arm Type
Experimental
Arm Description
Participants will be assigned to either a combination of 1) daratumumab plus teclistamab or 2) daratumumab plus talquetamab or 3) daratumumab plus talquetamab plus pomalidomide or 4) daratumumab plus teclistamab plus pomalidomide.
Arm Title
Part 2: Dose Expansion
Arm Type
Experimental
Arm Description
Participants will be treated with the RP2D(s) for selected treatment combinations determined in Part 1.
Intervention Type
Drug
Intervention Name(s)
Daratumumab
Other Intervention Name(s)
JNJ-54767414, Darzalex
Intervention Description
Participants will receive daratumumab.
Intervention Type
Drug
Intervention Name(s)
Talquetamab
Other Intervention Name(s)
JNJ-64407564
Intervention Description
Participants will receive talquetamab.
Intervention Type
Drug
Intervention Name(s)
Teclistamab
Other Intervention Name(s)
JNJ-64007957
Intervention Description
Participants will receive teclistamab.
Intervention Type
Drug
Intervention Name(s)
Pomalidomide
Intervention Description
Participants will receive pomalidomide.
Primary Outcome Measure Information:
Title
Part 1: Number of Participants With Dose Limiting Toxicity (DLT)
Description
The dose limiting toxicities are based on drug related adverse events and defined as any of the following events: hematological or non-hematological toxicity of grade 3 or higher.
Time Frame
Up to 52 Weeks
Title
Part 1: Number of Participants With Dose Limiting Toxicity by Severity
Description
The dose limiting toxicities are based on drug related adverse events and defined as any of the following events: hematological or non-hematological toxicity of grade 3 or higher.
Time Frame
Up to 52 Weeks
Title
Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product.
Time Frame
Up to 48 Weeks
Title
Part 2: Number of Participants With Adverse Events and SAEs by Severity
Description
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product.
Time Frame
Up to 48 Weeks
Secondary Outcome Measure Information:
Title
Serum Concentration of Daratumumab
Description
Serum concentration of daratumumab will be assessed.
Time Frame
Up to 52 Weeks
Title
Serum Concentration of Talquetamab
Description
Serum concentration of talquetamab will be assessed.
Time Frame
Up to 52 Weeks
Title
Serum Concentration of Teclistamab
Description
Serum concentration of teclistamab will be assessed.
Time Frame
Up to 52 Weeks
Title
Biomarker Assessment of Daratumumab
Description
Serum cytokine concentrations will be measured at the time of drug infusion of daratumumab for biomarker assessment.
Time Frame
Up to Cycle 7 Day 1 (each cycle of 28-days)
Title
Biomarker Assessment of Talquetamab
Description
Serum cytokine concentrations will be measured at the time of drug infusion of talquetamab for biomarker assessment.
Time Frame
Up to Cycle 7 Day 1 (each cycle of 28-days)
Title
Biomarker Assessment of Teclistamab
Description
Serum cytokine concentrations will be measured at the time of drug infusion of teclistamab for biomarker assessment.
Time Frame
Up to Cycle 7 Day 1 (each cycle of 28-days)
Title
Number of Participants With Anti-Drug Antibodies to Daratumumab
Description
Number of participants with anti-drug antibodies to daratumumab will be assessed.
Time Frame
Up to 52 Weeks
Title
Number of Participants With Anti-Drug Antibodies to Talquetamab
Description
Number of participants with anti-drug antibodies to talquetamab will be assessed.
Time Frame
Up to 52 Weeks
Title
Number of Participants With Anti-Drug Antibodies to Teclistamab
Description
Number of Participants with anti-drug antibodies to teclistamab will be assessed.
Time Frame
Up to 52 Weeks
Title
Overall Response Rate (ORR)
Description
ORR is defined as the percentage of participants who have a partial response (PR) or better according to the International Myeloma Working Group (IMWG) criteria.
Time Frame
Up to 48 Weeks
Title
Clinical Benefit Rate
Description
Clinical benefit rate (ORR + minimal response [MR]) is defined as the of participants who have a MR or better according to the IMWG criteria.
Time Frame
Up to 48 Weeks
Title
Duration of Response (DOR)
Description
DOR is defined as the time from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria.
Time Frame
Up to 48 Weeks
Title
Time to Response
Description
Time to response is defined as the time between date of first dose of study drug and the first efficacy evaluation that the participant has met all criteria for PR or better.
Time Frame
Up to 48 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 monoclonal protein (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 milligrams (mg)/24 hours; or Light chain multiple myeloma: Serum immunoglobulin (Ig) free light chain (FLC) >=10 milligrams per deciliter (mg/dL) and abnormal serum Ig kappa lambda FLC ratio Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at screening and at Cycle 1, Day 1 predose Female participants 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 1 day before the first dose of study drug Exclusion Criteria: 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 unless approved by sponsor Active Central nervous system involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, brain 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 Active hepatitis C infection as measured by positive hepatitis C virus- ribonucleotide (HCV)-RNA testing. Participants with a history of Hepatitis C virus antibody positivity must undergo HCV-RNA testing
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Wake Forest Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Vanderbilt - Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Medical College Of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Tom Baker Cancer Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
University Health Network (UHN) Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Universitatsklinikum Freiburg
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Universitaetsklinikum Hamburg Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Universitaetsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Universitätsklinikum Würzburg
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
VU Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
LUMC
City
Leiden
ZIP/Postal Code
2333ZA
Country
Netherlands
Facility Name
Hosp. Clinic I Provincial de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Inst. Cat. Doncologia-H Duran I Reynals
City
Barcelona
ZIP/Postal Code
08908
Country
Spain
Facility Name
Germans Trias I Pujol
City
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hosp. Univ. Fund. Jimenez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Clinica Univ. de Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hosp. Clinico Univ. de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency
Citations:
PubMed Identifier
32956453
Citation
Pillarisetti K, Powers G, Luistro L, Babich A, Baldwin E, Li Y, Zhang X, Mendonca M, Majewski N, Nanjunda R, Chin D, Packman K, Elsayed Y, Attar R, Gaudet F. Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma. Blood Adv. 2020 Sep 22;4(18):4538-4549. doi: 10.1182/bloodadvances.2020002393.
Results Reference
derived

Learn more about this trial

A Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Participants With Multiple Myeloma

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