Ignite Creation Date:
2025-12-24 @ 1:40 PM
Ignite Modification Date:
2026-02-27 @ 5:09 PM
Study NCT ID:
NCT04108195
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-12-05
First Post:
2019-09-26
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Participants With Multiple Myeloma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009101', 'term': 'Multiple Myeloma'}], 'ancestors': [{'id': 'D054219', 'term': 'Neoplasms, Plasma Cell'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D020141', 'term': 'Hemostatic Disorders'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D010265', 'term': 'Paraproteinemias'}, {'id': 'D001796', 'term': 'Blood Protein Disorders'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D006474', 'term': 'Hemorrhagic Disorders'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C556306', 'term': 'daratumumab'}, {'id': 'C000730985', 'term': 'talquetamab'}, {'id': 'C467566', 'term': 'pomalidomide'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 290}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2020-02-21', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-12', 'completionDateStruct': {'date': '2027-04-07', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-12-04', 'studyFirstSubmitDate': '2019-09-26', 'studyFirstSubmitQcDate': '2019-09-26', 'lastUpdatePostDateStruct': {'date': '2025-12-05', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2019-09-30', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-04-07', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Part 1: Number of Participants With Dose Limiting Toxicity (DLT)', 'timeFrame': 'Up to 52 Weeks', '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.'}, {'measure': 'Part 1: Number of Participants With Dose Limiting Toxicity by Severity', 'timeFrame': 'Up to 52 Weeks', '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.'}, {'measure': 'Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)', 'timeFrame': 'Up to 48 Weeks', '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.'}, {'measure': 'Part 2: Number of Participants With Adverse Events and SAEs by Severity', 'timeFrame': 'Up to 48 Weeks', '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.'}], 'secondaryOutcomes': [{'measure': 'Serum Concentration of Daratumumab', 'timeFrame': 'Up to 52 Weeks', 'description': 'Serum concentration of daratumumab will be assessed.'}, {'measure': 'Serum Concentration of Talquetamab', 'timeFrame': 'Up to 52 Weeks', 'description': 'Serum concentration of talquetamab will be assessed.'}, {'measure': 'Serum Concentration of Teclistamab', 'timeFrame': 'Up to 52 Weeks', 'description': 'Serum concentration of teclistamab will be assessed.'}, {'measure': 'Biomarker Assessment of Daratumumab', 'timeFrame': 'Up to Cycle 7 Day 1 (each cycle of 28-days)', 'description': 'Serum cytokine concentrations will be measured at the time of drug infusion of daratumumab for biomarker assessment.'}, {'measure': 'Biomarker Assessment of Talquetamab', 'timeFrame': 'Up to Cycle 7 Day 1 (each cycle of 28-days)', 'description': 'Serum cytokine concentrations will be measured at the time of drug infusion of talquetamab for biomarker assessment.'}, {'measure': 'Biomarker Assessment of Teclistamab', 'timeFrame': 'Up to Cycle 7 Day 1 (each cycle of 28-days)', 'description': 'Serum cytokine concentrations will be measured at the time of drug infusion of teclistamab for biomarker assessment.'}, {'measure': 'Number of Participants With Anti-Drug Antibodies to Daratumumab', 'timeFrame': 'Up to 52 Weeks', 'description': 'Number of participants with anti-drug antibodies to daratumumab will be assessed.'}, {'measure': 'Number of Participants With Anti-Drug Antibodies to Talquetamab', 'timeFrame': 'Up to 52 Weeks', 'description': 'Number of participants with anti-drug antibodies to talquetamab will be assessed.'}, {'measure': 'Number of Participants With Anti-Drug Antibodies to Teclistamab', 'timeFrame': 'Up to 52 Weeks', 'description': 'Number of Participants with anti-drug antibodies to teclistamab will be assessed.'}, {'measure': 'Overall Response Rate (ORR)', 'timeFrame': 'Up to 48 Weeks', '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.'}, {'measure': 'Clinical Benefit Rate', 'timeFrame': 'Up to 48 Weeks', '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.'}, {'measure': 'Duration of Response (DOR)', 'timeFrame': 'Up to 48 Weeks', '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.'}, {'measure': 'Time to Response', 'timeFrame': 'Up to 48 Weeks', '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.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Multiple Myeloma']}, 'referencesModule': {'references': [{'pmid': '40983036', 'type': 'DERIVED', 'citation': "Chari A, van de Donk NWCJ, Dholaria B, Weisel KC, Mateos MV, Goldschmidt H, Martin TG, Morillo D, Reece D, Rodriguez-Otero P, Bhutani M, D'Souza A, Oriol A, Rosinol L, Bahlis NJ, Vishwamitra D, Skerget S, Verona RI, Bakshi KK, Kang L, Prior TJ, Vandenberk L, Tolbert J, Lee S, Smit D, Wasch R. Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study. Blood. 2025 Sep 22:blood.2025029360. doi: 10.1182/blood.2025029360. Online ahead of print."}, {'pmid': '32956453', 'type': 'DERIVED', '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': "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 with or without pomalidomide 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 in combination with talquetamab and teclistamab with or without pomalidomide, 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), a Post-treatment Follow-up Period (after the last dose of study drug and will continue for up to 16 weeks for each subject), and a Long-term Extension Period. The study will end when one of the following occurs: 1) the study drug has received marketing authorization and, if regionally applicable, government reimbursement is available; 2) a long-term extension rollover study has commenced for participants who are still benefiting from study treatment as determined by their investigator; or 3) all participants have discontinued study treatment. Total duration of study is approximately 5 years and 6 months. 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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria\n* 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\n* 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\n* Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at screening and at Cycle 1, Day 1 predose\n* 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\n\nExclusion Criteria:\n\n* 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\n* Live, attenuated vaccine within 4 weeks prior to the first dose of study drug unless approved by sponsor\n* 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\n* 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\n* 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'}, 'identificationModule': {'nctId': 'NCT04108195', 'briefTitle': 'A Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Participants With Multiple Myeloma', 'organization': {'class': 'INDUSTRY', 'fullName': 'Janssen Research & Development, LLC'}, 'officialTitle': 'A Phase 1b Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Subjects With Multiple Myeloma', 'orgStudyIdInfo': {'id': 'CR108620'}, 'secondaryIdInfos': [{'id': '64407564MMY1002', 'type': 'OTHER', 'domain': 'Janssen Research & Development, LLC'}, {'id': '2019-000330-19', 'type': 'EUDRACT_NUMBER'}, {'id': '2023-503468-17-00', 'type': 'REGISTRY', 'domain': 'EUCT number'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Part 1: Dose Escalation', '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.', 'interventionNames': ['Drug: Daratumumab', 'Drug: Talquetamab', 'Drug: Teclistamab', 'Drug: Pomalidomide']}, {'type': 'EXPERIMENTAL', 'label': 'Part 2: Dose Expansion', 'description': 'Participants will be treated with the RP2D(s) for selected treatment combinations determined in Part 1.', 'interventionNames': ['Drug: Daratumumab', 'Drug: Talquetamab', 'Drug: Teclistamab', 'Drug: Pomalidomide']}], 'interventions': [{'name': 'Daratumumab', 'type': 'DRUG', 'otherNames': ['JNJ-54767414, Darzalex'], 'description': 'Participants will receive daratumumab.', 'armGroupLabels': ['Part 1: Dose Escalation', 'Part 2: Dose Expansion']}, {'name': 'Talquetamab', 'type': 'DRUG', 'otherNames': ['JNJ-64407564'], 'description': 'Participants will receive talquetamab.', 'armGroupLabels': ['Part 1: Dose Escalation', 'Part 2: Dose Expansion']}, {'name': 'Teclistamab', 'type': 'DRUG', 'otherNames': ['JNJ-64007957'], 'description': 'Participants will receive teclistamab.', 'armGroupLabels': ['Part 1: Dose Escalation', 'Part 2: Dose Expansion']}, {'name': 'Pomalidomide', 'type': 'DRUG', 'description': 'Participants will receive pomalidomide.', 'armGroupLabels': ['Part 1: Dose Escalation', 'Part 2: Dose Expansion']}]}, 'contactsLocationsModule': {'locations': [{'zip': '91010', 'city': 'Duarte', 'state': 'California', 'country': 'United States', 'facility': 'City of Hope National Medical Center', 'geoPoint': {'lat': 34.13945, 'lon': -117.97729}}, {'zip': '92618', 'city': 'Irvine', 'state': 'California', 'country': 'United States', 'facility': 'City of Hope Orange County Lennar Foundation Cancer Center', 'geoPoint': {'lat': 33.66946, 'lon': -117.82311}}, {'zip': '94143', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': 'University of California San Francisco', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '10011', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'The Blavatnik Family Chelsea Medical Center at Mount Sinai', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '10029', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Mount Sinai Medical Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '28204', 'city': 'Charlotte', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Levine Cancer Institute', 'geoPoint': {'lat': 35.22709, 'lon': -80.84313}}, {'zip': '27157', 'city': 'Winston-Salem', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Wake Forest Baptist Medical Center', 'geoPoint': {'lat': 36.09986, 'lon': -80.24422}}, {'zip': '19104', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'University of Pennsylvania', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}, {'zip': '37232', 'city': 'Nashville', 'state': 'Tennessee', 'country': 'United States', 'facility': 'Vanderbilt Ingram Cancer Center', 'geoPoint': {'lat': 36.16589, 'lon': -86.78444}}, {'zip': '53226', 'city': 'Milwaukee', 'state': 'Wisconsin', 'country': 'United States', 'facility': 'Medical College Of Wisconsin', 'geoPoint': {'lat': 43.0389, 'lon': -87.90647}}, {'zip': 'T2N 5G2', 'city': 'Calgary', 'state': 'Alberta', 'country': 'Canada', 'facility': 'Arthur J E Child Comprehensive Cancer Centre', 'geoPoint': {'lat': 51.05011, 'lon': -114.08529}}, {'zip': 'M5G 2M9', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'University Health Network UHN Princess Margaret Cancer Centre', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'zip': '79106', 'city': 'Freiburg im Breisgau', 'country': 'Germany', 'facility': 'Universitatsklinikum Freiburg', 'geoPoint': {'lat': 47.9959, 'lon': 7.85222}}, {'zip': '20246', 'city': 'Hamburg', 'country': 'Germany', 'facility': 'Universitaetsklinikum Hamburg Eppendorf', 'geoPoint': {'lat': 53.55073, 'lon': 9.99302}}, {'zip': '69120', 'city': 'Heidelberg', 'country': 'Germany', 'facility': 'Universitaetsklinikum Heidelberg', 'geoPoint': {'lat': 49.40768, 'lon': 8.69079}}, {'zip': '97080', 'city': 'Würzburg', 'country': 'Germany', 'facility': 'Universitatsklinikum Wurzburg', 'geoPoint': {'lat': 49.79391, 'lon': 9.95121}}, {'zip': '1081 HV', 'city': 'Amsterdam', 'country': 'Netherlands', 'facility': 'VU Medisch Centrum', 'geoPoint': {'lat': 52.37403, 'lon': 4.88969}}, {'zip': '2333ZA', 'city': 'Leiden', 'country': 'Netherlands', 'facility': 'LUMC', 'geoPoint': {'lat': 52.15833, 'lon': 4.49306}}, {'zip': '08036', 'city': 'Barcelona', 'country': 'Spain', 'facility': 'Hosp Clinic de Barcelona', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'zip': '08908', 'city': 'Barcelona', 'country': 'Spain', 'facility': 'Inst. Cat. Doncologia-H Duran I Reynals', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'zip': '08916', 'city': 'Barcelona', 'country': 'Spain', 'facility': 'Germans Trias I Pujol', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'zip': '28040', 'city': 'Madrid', 'country': 'Spain', 'facility': 'Hosp Univ Fund Jimenez Diaz', 'geoPoint': {'lat': 40.4165, 'lon': -3.70256}}, {'zip': '31008', 'city': 'Pamplona', 'country': 'Spain', 'facility': 'Clinica Univ. de Navarra', 'geoPoint': {'lat': 42.81687, 'lon': -1.64323}}, {'zip': '37007', 'city': 'Salamanca', 'country': 'Spain', 'facility': 'Hosp Clinico Univ de Salamanca', 'geoPoint': {'lat': 40.96882, 'lon': -5.66388}}], 'overallOfficials': [{'name': 'Janssen Research & Development, LLC Clinical Trial', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Janssen Research & Development, LLC'}]}, 'ipdSharingStatementModule': {'url': 'https://www.janssen.com/clinical-trials/transparency', 'ipdSharing': 'YES', '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'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Janssen Research & Development, LLC', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}