- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04108195
A Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Participants With Multiple Myeloma
April 23, 2024 updated by: Janssen Research & Development, LLC
A Phase 1b Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Subjects With Multiple Myeloma
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
290
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Alberta
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Calgary, Alberta, Canada, T2N 4N2
- Tom Baker Cancer Centre
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Ontario
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Toronto, Ontario, Canada, M5G 2M9
- University Health Network (UHN) Princess Margaret Cancer Centre
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Freiburg, Germany, 79106
- Universitätsklinikum Freiburg
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Hamburg, Germany, 20246
- Universitaetsklinikum Hamburg Eppendorf
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Heidelberg, Germany, 69120
- Universitaetsklinikum Heidelberg
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Wuerzburg, Germany, 97080
- Universitatsklinikum Wurzburg
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Amsterdam, Netherlands, 1081 HV
- VU Medisch Centrum
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Leiden, Netherlands, 2333ZA
- LUMC
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Barcelona, Spain, 08908
- Inst. Cat. Doncologia-H Duran I Reynals
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Barcelona, Spain, 08916
- Germans Trias I Pujol
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Barcelona, Spain, 08036
- Hosp. Clinic de Barcelona
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Madrid, Spain, 28040
- Hosp. Univ. Fund. Jimenez Diaz
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Pamplona, Spain, 31008
- Clinica Univ. de Navarra
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Salamanca, Spain, 37007
- Hosp. Clinico Univ. de Salamanca
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California
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Duarte, California, United States, 91010
- City of Hope National Medical Center
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San Francisco, California, United States, 94143
- University of California San Francisco
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New York
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New York, New York, United States, 10029
- Mount Sinai Medical Center
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North Carolina
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Charlotte, North Carolina, United States, 28204
- Levine Cancer Institute
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Winston-Salem, North Carolina, United States, 27157
- Wake Forest Baptist Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt - Ingram Cancer Center
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Wisconsin
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Milwaukee, Wisconsin, United States, 53226
- Medical College Of Wisconsin
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Part 1: Dose Escalation
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.
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Participants will receive teclistamab.
Other Names:
Participants will receive daratumumab.
Other Names:
Participants will receive pomalidomide.
Participants will receive talquetamab.
Other Names:
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Experimental: Part 2: Dose Expansion
Participants will be treated with the RP2D(s) for selected treatment combinations determined in Part 1.
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Participants will receive teclistamab.
Other Names:
Participants will receive daratumumab.
Other Names:
Participants will receive pomalidomide.
Participants will receive talquetamab.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Part 1: Number of Participants With Dose Limiting Toxicity (DLT)
Time Frame: Up to 52 Weeks
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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.
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Up to 52 Weeks
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Part 1: Number of Participants With Dose Limiting Toxicity by Severity
Time Frame: Up to 52 Weeks
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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.
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Up to 52 Weeks
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Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to 48 Weeks
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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.
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Up to 48 Weeks
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Part 2: Number of Participants With Adverse Events and SAEs by Severity
Time Frame: Up to 48 Weeks
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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.
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Up to 48 Weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Serum Concentration of Daratumumab
Time Frame: Up to 52 Weeks
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Serum concentration of daratumumab will be assessed.
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Up to 52 Weeks
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Serum Concentration of Talquetamab
Time Frame: Up to 52 Weeks
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Serum concentration of talquetamab will be assessed.
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Up to 52 Weeks
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Serum Concentration of Teclistamab
Time Frame: Up to 52 Weeks
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Serum concentration of teclistamab will be assessed.
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Up to 52 Weeks
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Biomarker Assessment of Daratumumab
Time Frame: Up to Cycle 7 Day 1 (each cycle of 28-days)
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Serum cytokine concentrations will be measured at the time of drug infusion of daratumumab for biomarker assessment.
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Up to Cycle 7 Day 1 (each cycle of 28-days)
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Biomarker Assessment of Talquetamab
Time Frame: Up to Cycle 7 Day 1 (each cycle of 28-days)
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Serum cytokine concentrations will be measured at the time of drug infusion of talquetamab for biomarker assessment.
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Up to Cycle 7 Day 1 (each cycle of 28-days)
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Biomarker Assessment of Teclistamab
Time Frame: Up to Cycle 7 Day 1 (each cycle of 28-days)
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Serum cytokine concentrations will be measured at the time of drug infusion of teclistamab for biomarker assessment.
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Up to Cycle 7 Day 1 (each cycle of 28-days)
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Number of Participants With Anti-Drug Antibodies to Daratumumab
Time Frame: Up to 52 Weeks
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Number of participants with anti-drug antibodies to daratumumab will be assessed.
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Up to 52 Weeks
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Number of Participants With Anti-Drug Antibodies to Talquetamab
Time Frame: Up to 52 Weeks
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Number of participants with anti-drug antibodies to talquetamab will be assessed.
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Up to 52 Weeks
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Number of Participants With Anti-Drug Antibodies to Teclistamab
Time Frame: Up to 52 Weeks
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Number of Participants with anti-drug antibodies to teclistamab will be assessed.
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Up to 52 Weeks
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Overall Response Rate (ORR)
Time Frame: Up to 48 Weeks
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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.
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Up to 48 Weeks
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Clinical Benefit Rate
Time Frame: Up to 48 Weeks
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Clinical benefit rate (ORR + minimal response [MR]) is defined as the of participants who have a MR or better according to the IMWG criteria.
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Up to 48 Weeks
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Duration of Response (DOR)
Time Frame: Up to 48 Weeks
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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.
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Up to 48 Weeks
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Time to Response
Time Frame: Up to 48 Weeks
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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.
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Up to 48 Weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 21, 2020
Primary Completion (Estimated)
September 9, 2024
Study Completion (Estimated)
August 22, 2025
Study Registration Dates
First Submitted
September 26, 2019
First Submitted That Met QC Criteria
September 26, 2019
First Posted (Actual)
September 30, 2019
Study Record Updates
Last Update Posted (Estimated)
April 24, 2024
Last Update Submitted That Met QC Criteria
April 23, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunologic Factors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Pomalidomide
- Daratumumab
Other Study ID Numbers
- CR108620
- 2019-000330-19 (EudraCT Number)
- 64407564MMY1002 (Other Identifier: Janssen Research & Development, LLC)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD 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
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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SCRI Development Innovations, LLCJanssen Research & Development, LLCRecruiting
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