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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| ClinicalTrials.gov Identifier: NCT04108195 |
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Recruitment Status :
Active, not recruiting
First Posted : September 30, 2019
Last Update Posted : May 31, 2023
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Sponsor:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Janssen Research & Development, LLC
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Myeloma | Drug: Daratumumab Drug: Talquetamab Drug: Teclistamab Drug: Pomalidomide | Phase 1 |
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 (Clinical Trial) |
| Actual Enrollment : | 294 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | February 21, 2020 |
| Estimated Primary Completion Date : | September 9, 2024 |
| Estimated Study Completion Date : | September 9, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Multiple myeloma
MedlinePlus related topics:
Multiple Myeloma
Drug Information available for:
Daratumumab
| 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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Drug: Daratumumab
Participants will receive daratumumab.
Other Name: JNJ-54767414, Darzalex Drug: Talquetamab Participants will receive talquetamab.
Other Name: JNJ-64407564 Drug: Teclistamab Participants will receive teclistamab.
Other Name: JNJ-64007957 Drug: Pomalidomide Participants will receive pomalidomide. |
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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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Drug: Daratumumab
Participants will receive daratumumab.
Other Name: JNJ-54767414, Darzalex Drug: Talquetamab Participants will receive talquetamab.
Other Name: JNJ-64407564 Drug: Teclistamab Participants will receive teclistamab.
Other Name: JNJ-64007957 Drug: Pomalidomide Participants will receive pomalidomide. |
Primary Outcome Measures :
- Part 1: Number of Participants With Dose Limiting Toxicity (DLT) [ Time Frame: Up to 52 Weeks ]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 [ Time Frame: Up to 52 Weeks ]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) [ Time Frame: Up to 48 Weeks ]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 [ Time Frame: Up to 48 Weeks ]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 [ Time Frame: Up to 52 Weeks ]Serum concentration of daratumumab will be assessed.
- Serum Concentration of Talquetamab [ Time Frame: Up to 52 Weeks ]Serum concentration of talquetamab will be assessed.
- Serum Concentration of Teclistamab [ Time Frame: Up to 52 Weeks ]Serum concentration of teclistamab will be assessed.
- Biomarker Assessment of Daratumumab [ Time Frame: Up to Cycle 7 Day 1 (each cycle of 28-days) ]Serum cytokine concentrations will be measured at the time of drug infusion of daratumumab for biomarker assessment.
- Biomarker Assessment of Talquetamab [ Time Frame: Up to Cycle 7 Day 1 (each cycle of 28-days) ]Serum cytokine concentrations will be measured at the time of drug infusion of talquetamab for biomarker assessment.
- Biomarker Assessment of Teclistamab [ Time Frame: Up to Cycle 7 Day 1 (each cycle of 28-days) ]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 [ Time Frame: Up to 52 Weeks ]Number of participants with anti-drug antibodies to daratumumab will be assessed.
- Number of Participants With Anti-Drug Antibodies to Talquetamab [ Time Frame: Up to 52 Weeks ]Number of participants with anti-drug antibodies to talquetamab will be assessed.
- Number of Participants With Anti-Drug Antibodies to Teclistamab [ Time Frame: Up to 52 Weeks ]Number of Participants with anti-drug antibodies to teclistamab will be assessed.
- Overall Response Rate (ORR) [ Time Frame: Up to 48 Weeks ]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 [ Time Frame: Up to 48 Weeks ]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) [ Time Frame: Up to 48 Weeks ]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 Frame: Up to 48 Weeks ]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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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04108195
Locations
Show 22 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
| Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Janssen Research & Development, LLC |
| ClinicalTrials.gov Identifier: | NCT04108195 |
| Other Study ID Numbers: |
CR108620 2019-000330-19 ( EudraCT Number ) 64407564MMY1002 ( Other Identifier: Janssen Research & Development, LLC ) |
| First Posted: | September 30, 2019 Key Record Dates |
| Last Update Posted: | May 31, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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 |
| URL: | https://www.janssen.com/clinical-trials/transparency |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders |
Immunoproliferative Disorders Immune System Diseases Daratumumab Pomalidomide Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors |