GMMG-HD10 / DSMM-XX / 64007957MMY2003, MajesTEC-5

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified November 2025 by University of Heidelberg Medical Center
Sponsor
University of Heidelberg Medical Center
Information Provided by (Responsible Party)
Marc Raab
Clinicaltrials.gov Identifier
NCT05695508
Other Study ID Numbers:
GMMG-HD10/DSMM-XX
First Submitted
November 29, 2022
First Posted
January 24, 2023
Last Update Posted
December 23, 2025
Last Verified
November 2025

ClinicalTrials.gov processed this data on December 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

OVERALL DESIGN:

160 participants will be enrolled with 10 participants in Arm A, 20 participants in Arm A1, 20 participants in Arm B, 10 participants in Arms C and 10 in C2, 20 participants in Arm D, 10 participants in each Arm E, E1 and optionally F and F, and 20 participants in Arm G. Cohorts may be further expanded.

Arms A, A1, B, D, E, E1, F, F1 will receive Induction therapy of 6 cycles (28-days each):

Treatment: Tec-DRd (Arm A, A1), Tec-DVRd (Arm B), Tal-DRd (Arms E, E1), Tal-DVRd (Arms F, F1) followed by HDT and a single ASCT according to local SoC treatment. Thereafter a Maintenance Therapy of maximum 18 cycles with either Tec-D (Arms A, A1, B, E, F) or Tal-D (E1, F1) is performed.

Arm D will receive 6 28-days cycles Tec-DVRd induction followed by 18 cycles Tec-Tal. Arm G will receive 6 28-day cycles of JNJ-79635322-DRd induction, followed by JNJ-79635322-D. No HDT ASCT will be performed in Arm D and Arm G.

In Arm C and C2 participants will enter the study for maintenance treatment of 18 cycles with Tec-D (Arm C) or Tal-DR (Arm C2) , after induction, HDT and ASCT according to local SoC (outside of the study).

Participants will receive maintenance treatment or following induction treatment (Arm D and G) for a maximum of 18 cycles or until confirmed progressive disease, death, intolerable toxicity, loss to follow-up, or consent withdrawal, whichever comes first. An optional end of treatment is possible for patients who have 12 months sustained MRD negativity.

Periodic safety evaluations will be conducted to ensure that treatment is safe and tolerable. Upon treatment discontinuation, an EOT Visit will be conducted. Thereafter, the participant will continue in the Follow-up Phase until death, withdrawal of consent, loss to follow-up, or end of the study, whichever occurs first.

Condition or DiseaseIntervention/Treatment
Multiple Myeloma
Drug: Teclistamab (Tec)Drug: Teclistamab (Tec)Drug: Teclistamab (Tec)Drug: Teclistamab (Tec)Drug: DaratumumabDrug: Teclistamab (Tec)Drug: Teclistamab (Tec)Drug: DaratumumabDrug: Teclistamab (Tec)Drug: DaratumumabDrug: Daratumumab

Study Design

Study TypeInterventional
Actual Enrollment160 participants
Design AllocationNon-Randomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA Phase 2 Study to Evaluate Safety and Efficacy of Teclistamab-, Talquetamab-, and JNJ-79635322-based Combination Regimens in Participants With Newly Diagnosed Transplant Eligible Multiple Myeloma
Study Start DateNovember 30, 2022
Actual Primary Completion Date2yrs 3mos from now
Actual Study Completion Date3yrs 3mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Arm A Tec-DRd Induction and Tec-D Maintenance
Arm A participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab SC, lenalidomide and dexamethasone in 6 cycles of induction therapy, followed by teclistamab SC injection in combination with daratumumab SC in maximum 18 cycles of maintenance therapy.
Drug: Teclistamab (Tec)
Subcutaneous administration of Teclistamab
Arm B Tec-DVRd Induction and Tec-D Maintenance
Arm B participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab SC, lenalidomide, dexamethasone and bortezomib in 6 cycles of induction therapy, followed by teclistamab SC injection in combination with daratumumab SC in maximum 18 cycles of maintenance therapy.
Drug: Teclistamab (Tec)
Subcutaneous administration of Teclistamab
Arm C Tec-D Maintenance
Arm C participants will receive maximum 18 cycles of teclistamab SC injection in combination with daratumumab SC and lenalidomide as maintenance therapy.
Drug: Teclistamab (Tec)
Subcutaneous administration of Teclistamab
Arm A1 Tec-DRd Induction and Tec-D Maintenance
Arm A1 participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab SC, lenalidomide and dexamethasone in 6 cycles of induction therapy, followed by teclistamab SC injection in combination with daratumumab SC in maximum 18 cycles of maintenance therapy.
Drug: Teclistamab (Tec)
Subcutaneous administration of Teclistamab
Arm C2 Tal-DR Maintenance
Arm C2 participants will receive maximum 18 cycles of talquetamab SC injection in combination with daratumumab SC and lenalidomide as maintenance therapy.
Drug: Daratumumab
Subcutaneous administration of Daratumumab
Arm D Tec-DRd Induction and Tec-Tal following induction
Arm D participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab SC, lenalidomide and dexamethasone in 6 cycles of induction therapy, followed by a combination of teclistamab and talquetamab SC injection in maximum 18 cycles of following induction therapy.
Drug: Teclistamab (Tec)
Subcutaneous administration of Teclistamab
Arm E Tal-DRd Induction and Tec-D Maintenance
Arm E participants will receive talquetamab as subcutaneous (SC) injection in combination with daratumumab SC, lenalidomide and dexamethasone in 6 cycles of induction therapy, followed by teclistamab SC injection in combination with daratumumab SC in maximum 18 cycles of maintenance therapy.
Drug: Teclistamab (Tec)
Subcutaneous administration of Teclistamab
Arm E1 Tal-DRd Induction and Tal-D Maintenance
Arm E1 participants will receive talquetamab as subcutaneous (SC) injection in combination with daratumumab SC, lenalidomide and dexamethasone in 6 cycles of induction therapy, followed by talquetamab SC injection in combination with daratumumab SC in maximum 18 cycles of maintenance therapy.
Drug: Daratumumab
Subcutaneous administration of Daratumumab
Arm F Tal-DVRd Induction and Tec-D Maintenance
Arm F participants will receive talquetamab as subcutaneous (SC) injection in combination with daratumumab SC, bortezomib, lenalidomide and dexamethasone in 6 cycles of induction therapy, followed by teclistamab SC injection in combination with daratumumab SC in maximum 18 cycles of maintenance therapy.
Drug: Teclistamab (Tec)
Subcutaneous administration of Teclistamab
Arm F1 Tal-DVRd Induction and Tal-D Maintenance
Arm F1 participants will receive talquetamab as subcutaneous (SC) injection in combination with daratumumab SC, bortezomib, lenalidomide and dexamethasone in 6 cycles of induction therapy, followed by talquetamab SC injection in combination with daratumumab SC in maximum 18 cycles of maintenance therapy.
Drug: Daratumumab
Subcutaneous administration of Daratumumab
Arm-G JNJ-79635322-DRd induction - JNJ-79635322-D following ind
Arm G participants will receive six 28-day cycles of JNJ-79635322-DRd induction, followed byJNJ-79635322-D treatment for a maximum of eighteen 28-day cycles or until confirmed PD, death, intolerable toxicity, loss to follow-up, or consent withdrawal, whichever comes first. Tec-Tal or JNJ-79635322-D treatment can be discontinued when 12 months of sustained MRD negativity has been observed during the study.
Drug: Daratumumab
Subcutaneous administration of Daratumumab

Outcome Measures

Primary Outcome Measures
  1. number of incidence and severity of adverse events [safety and tolerability]
Secondary Outcome Measures
  1. MRD negativity rate
    MRD negativity rate measured by Flow Cytometry
  2. Response on therapy [efficacy]
    Response on therapy according to IMWG: * Overall Response Rate (ORR) (at least a PR or better) * Complete Response (CR) or better * Very Good Partial Response (VGPR) or better * Duration of Response (DoR)
  3. Progression Free Survival [efficacy]
  4. Serum concentration of teclistamab, talquetamab and daratumumab [pharmacokinetics]
  5. Presence of ADAs to teclistamab, talquetamab and daratumumab [immunogenicity]
  6. Stem cell yield
    feasibility of successful transplantation
  7. days to engraftment
    feasibility of successful transplantation

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
\- 18 years of age to 70 years of age, inclusive
Have an ECOG performance status score of 0 to 2 at screening
Have an ECOG performance status score of 0 to 2 at screening and immediately prior to the start of administration of study treatment Participants in Arms A, A1, B, D, E, E1, F, F1 and G must also satisfy all of the following criteria to be enrolled in the study: 1\. Documented multiple myeloma requiring treatment as defined by the criteria below: 1. Multiple myeloma diagnosis according to the IMWG diagnostic criteria 2. Measurable disease at screening as defined by any of the following: 1\. Serum M-protein level ≥1.0 g/dL or 2. Urine M-protein level ≥200 mg/24 hours or 3. Serum immunoglobulin free light chain level ≥10 mg/dL and abnormal serum free light chain ratio 2. Newly diagnosed participants for whom HDT and ASCT is part of the intended treatment plan (except Arm D and G participants). Participants Arm C and C2 must also satisfy all of the following criteria: 1. Newly diagnosed multiple myeloma according to IMWG criteria. 2. Must have received 4 to 6 28-day cycles of 3 or 4 drug-induction therapy that includes a proteasome inhibitor and/or an IMiD with or without anti-CD38 monoclonal antibody and a single or tandem ASCT. Post-ASCT consolidation is permitted for up to 2 cycles as long as the total number of induction plus consolidation cycles does not exceed 6. 3 Must have received only one line of therapy and achieved at least a PR as per IMWG 2016 response criteria based on the investigator's assessment. Participants with plasmacytomas at the time of diagnosis must meet IMWG 2016 response criteria for ≥PR based on repeat imaging utilizing the same modality 4. Must have received HDT and ASCT within 12 months of the start of induction therapy and be within 6 months of the last ASCT (7 months for participants who received consolidation) at the time of enrollment.
Exclusion Criteria
\- CNS involvement or clinical signs of meningeal involvement of multiple myeloma. \- Stroke or seizure within 6 months prior study start Cycle1 Day1. \- History of transplantations requiring immunosuppressive therapy. \- Seropositive for HIV, HEP B, Active Hep C infection (details see protocol). \- COPD with a FEV1 \<50% of predicted normal. \- Moderate /severe persistent asthma within the past 2 years or any uncontrolled asthma. Exclude if FEV1 \<50% of predicted normal. \- Concurrent medical or psychiatric condition or disease that is likely to interfere with study procedures, or that in the investigators opinion would constitute a hazard for participants. \- Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug/excipients. \- Pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of any study treatment regimen. \- Plans to father a child while enrolled in this study or within 100 days after the last dose of any component of the study treatment regimen. Arm A, A1, B, D, E, E1, F, F1
Prior or current systemic therapy or stem cell transplant for any plasma cell dyscrasia, with the exception of emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment.
Arm B only: Peripheral neuropathy or neuropathic pain Grade 2 or higher as defined by the NCI-CTCAE Version 5. Due to a potential interaction with bortezomib, received a strong CYP3A4 inducer within 5 half-lives prior to enrollment Arm C and C2 \- Discontinued treatment due to any AE related to lenalidomide as determined by the investigator.
Progressed on multiple myeloma therapy at any time prior to screening.
Received a cumulative dose of corticosteroids equivalent to ≥40 mg of dexamethasone within the 14 day period before the start of study treatment administration.
Intolerant to the starting dose of lenalidomide (10 mg). For further details on inclusion/exclusion criteria please refer to the study protocol.

Contacts and Locations

Sponsors and CollaboratorsUniversity of Heidelberg Medical Center
Locations
Charité University Medicin Berlin | Berlin , Germany, 12203Clinic Chemnitz gGmbH | Chemnitz , Germany, 09113University Clinic Technical University Dresden | Dresden , Germany, 01307University Clinic Düsseldorf | Düsseldorf , Germany, 40225University Clinic Freiburg | Freiburg im Breisgau , Germany, 79106Hamburg University Clinic Eppendorf | Hamburg , Germany, 20246Asklepios Clinic Hamburg Altona | Hamburg , Germany, 22763University Hospital Heidelberg | Heidelberg , Germany, 69120University Clinic Schleswig-Holstein Campus Kiel | Kiel , Germany, 24105Technical University Munich | Munich , Germany, 81675University Würzburg | Würzburg , Germany,