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

NCT05695508 | Recruiting Phase 2

• 1 other identifier: GMMG-HD10/DSMM-XX
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 11

Brief Summary

A 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 OBJECTIVES: To evaluate the safety and tolerability of teclistamab-, talquetamab-, and JNJ-79635322-based combination regimens over the entire treatment phase for each arm, in participants with ND-TEMM To evaluate the efficacy of teclistamab- and talquetamab-based combination regimens as induction and post-transplant maintenance treatments; JNJ-79635322-based combinations as induction and as replacement for HDT+ASCT following induction; and teclistamab in combination with talquetamab

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• number of incidence and severity of adverse events [safety and tolerability]

  through study completion, up to 28 months

Secondary Outcomes (7)

• MRD negativity rate

  after 6 cycles (each cycle is 28 days) induction therapy (app.month 6), after High Dose Therapy (app. month 10), after 18 cycles (each cycle is 28 days) of maintenance therapy (app. month 28)

• Response on therapy [efficacy]

  after each cycle (each cycle is 28 days) induction ( app. at month 1,2,...,6), after High Dose therapy (app. month 10), after each cycle (each cycle is 28 days) of maintenance (app. at month 11,12, ...28), during FU every 3 months (app. up to 3-4 years)

• Progression Free Survival [efficacy]

  From randomization to the date of disease progression to death (app. up to 3-4 years)

• Serum concentration of teclistamab, talquetamab and daratumumab [pharmacokinetics]

  through study completion, up to 28 months

• Presence of ADAs to teclistamab, talquetamab and daratumumab [immunogenicity]

  through study completion, up to 28 months

Study Arms (11)

Arm A Tec-DRd Induction and Tec-D Maintenance

EXPERIMENTAL

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); Drug: Daratumumab; Drug: Dexamethasone; Drug: Lenalidomide

Arm B Tec-DVRd Induction and Tec-D Maintenance

EXPERIMENTAL

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); Drug: Daratumumab; Drug: Dexamethasone; Drug: Lenalidomide; Drug: Bortezomib

Arm C Tec-D Maintenance

EXPERIMENTAL

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); Drug: Daratumumab

Arm A1 Tec-DRd Induction and Tec-D Maintenance

EXPERIMENTAL

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); Drug: Daratumumab; Drug: Dexamethasone; Drug: Lenalidomide

Arm C2 Tal-DR Maintenance

EXPERIMENTAL

Arm C2 participants will receive maximum 18 cycles of talquetamab SC injection in combination with daratumumab SC and lenalidomide as maintenance therapy.

Drug: Daratumumab; Drug: Lenalidomide; Drug: Talquetamab

Arm D Tec-DRd Induction and Tec-Tal following induction

EXPERIMENTAL

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); Drug: Daratumumab; Drug: Dexamethasone; Drug: Lenalidomide; Drug: Talquetamab

Arm E Tal-DRd Induction and Tec-D Maintenance

EXPERIMENTAL

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); Drug: Daratumumab; Drug: Dexamethasone; Drug: Lenalidomide; Drug: Talquetamab

Arm E1 Tal-DRd Induction and Tal-D Maintenance

EXPERIMENTAL

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; Drug: Dexamethasone; Drug: Lenalidomide; Drug: Talquetamab

Arm F Tal-DVRd Induction and Tec-D Maintenance

EXPERIMENTAL

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); Drug: Daratumumab; Drug: Dexamethasone; Drug: Lenalidomide; Drug: Bortezomib; Drug: Talquetamab

Arm F1 Tal-DVRd Induction and Tal-D Maintenance

EXPERIMENTAL

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; Drug: Dexamethasone; Drug: Lenalidomide; Drug: Bortezomib; Drug: Talquetamab

Arm-G JNJ-79635322-DRd induction - JNJ-79635322-D following ind

EXPERIMENTAL

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; Drug: Dexamethasone; Drug: Lenalidomide; Drug: JNJ-79635322

Interventions

Teclistamab (Tec) DRUG

Subcutaneous administration of Teclistamab

Also known as: JNJ-64007957

Arm A Tec-DRd Induction and Tec-D Maintenance; Arm A1 Tec-DRd Induction and Tec-D Maintenance; Arm B Tec-DVRd Induction and Tec-D Maintenance; Arm C Tec-D Maintenance; Arm D Tec-DRd Induction and Tec-Tal following induction; Arm E Tal-DRd Induction and Tec-D Maintenance; Arm F Tal-DVRd Induction and Tec-D Maintenance

Daratumumab DRUG

Subcutaneous administration of Daratumumab

Arm A Tec-DRd Induction and Tec-D Maintenance; Arm A1 Tec-DRd Induction and Tec-D Maintenance; Arm B Tec-DVRd Induction and Tec-D Maintenance; Arm C Tec-D Maintenance; Arm C2 Tal-DR Maintenance; Arm D Tec-DRd Induction and Tec-Tal following induction; Arm E Tal-DRd Induction and Tec-D Maintenance; Arm E1 Tal-DRd Induction and Tal-D Maintenance; Arm F Tal-DVRd Induction and Tec-D Maintenance; Arm F1 Tal-DVRd Induction and Tal-D Maintenance; Arm-G JNJ-79635322-DRd induction - JNJ-79635322-D following ind

Dexamethasone DRUG

administered i.v. or orally

Arm A Tec-DRd Induction and Tec-D Maintenance; Arm A1 Tec-DRd Induction and Tec-D Maintenance; Arm B Tec-DVRd Induction and Tec-D Maintenance; Arm D Tec-DRd Induction and Tec-Tal following induction; Arm E Tal-DRd Induction and Tec-D Maintenance; Arm E1 Tal-DRd Induction and Tal-D Maintenance; Arm F Tal-DVRd Induction and Tec-D Maintenance; Arm F1 Tal-DVRd Induction and Tal-D Maintenance; Arm-G JNJ-79635322-DRd induction - JNJ-79635322-D following ind

Lenalidomide DRUG

Administration oral

Arm A Tec-DRd Induction and Tec-D Maintenance; Arm A1 Tec-DRd Induction and Tec-D Maintenance; Arm B Tec-DVRd Induction and Tec-D Maintenance; Arm C2 Tal-DR Maintenance; Arm D Tec-DRd Induction and Tec-Tal following induction; Arm E Tal-DRd Induction and Tec-D Maintenance; Arm E1 Tal-DRd Induction and Tal-D Maintenance; Arm F Tal-DVRd Induction and Tec-D Maintenance; Arm F1 Tal-DVRd Induction and Tal-D Maintenance; Arm-G JNJ-79635322-DRd induction - JNJ-79635322-D following ind

Bortezomib DRUG

Subcutaneous administration

Arm B Tec-DVRd Induction and Tec-D Maintenance; Arm F Tal-DVRd Induction and Tec-D Maintenance; Arm F1 Tal-DVRd Induction and Tal-D Maintenance

Talquetamab DRUG

Subcutaneous administration of Daratumumab

Arm C2 Tal-DR Maintenance; Arm D Tec-DRd Induction and Tec-Tal following induction; Arm E Tal-DRd Induction and Tec-D Maintenance; Arm E1 Tal-DRd Induction and Tal-D Maintenance; Arm F Tal-DVRd Induction and Tec-D Maintenance; Arm F1 Tal-DVRd Induction and Tal-D Maintenance

JNJ-79635322 DRUG

Subcutaneous administration

Arm-G JNJ-79635322-DRd induction - JNJ-79635322-D following ind

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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:
• \. Documented multiple myeloma requiring treatment as defined by the criteria below:
• Multiple myeloma diagnosis according to the IMWG diagnostic criteria
• Measurable disease at screening as defined by any of the following:
• \. 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:
• Newly diagnosed multiple myeloma according to IMWG criteria.
• 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.
• 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.

You may not qualify if:

• \- 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

Sponsors & Collaborators

• University of Heidelberg Medical Center: lead
• Janssen Research & Development, LLC: collaborator
• Deutsche Studiengruppe Multiples Myelom (DSMM): collaborator

Study Sites (11)

Charité University Medicin Berlin

Berlin, 12203, Germany

RECRUITING

Clinic Chemnitz gGmbH

Chemnitz, 09113, Germany

RECRUITING

University Clinic Technical University Dresden

Dresden, 01307, Germany

RECRUITING

University Clinic Düsseldorf

Düsseldorf, 40225, Germany

RECRUITING

University Clinic Freiburg

Freiburg im Breisgau, 79106, Germany

RECRUITING

Hamburg University Clinic Eppendorf

Hamburg, 20246, Germany

RECRUITING

Asklepios Clinic Hamburg Altona

Hamburg, 22763, Germany

RECRUITING

University Hospital Heidelberg

Heidelberg, 69120, Germany

RECRUITING

University Clinic Schleswig-Holstein Campus Kiel

Kiel, 24105, Germany

RECRUITING

Technical University Munich

Munich, 81675, Germany

RECRUITING

University Würzburg

Würzburg, Germany

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Focal Adhesion Protein-Tyrosine Kinases; daratumumab; Dexamethasone; Lenalidomide; Bortezomib; talquetamab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Protein-Tyrosine Kinases; Protein Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Intracellular Signaling Peptides and Proteins; Proteins; Amino Acids, Peptides, and Proteins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines

Central Study Contacts

Marc S Raab, Prof. Dr. med

CONTACT

+49 6221 56; s.gmmg@med.uni-heidelberg.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Model Details: Induction phase contains 6 cycles of Tec-DRd \[Arm A, A1, D\] , Tec-DVRd \[Arm B\], Tal-DRd \[Arm E, E1\] or Tal-DVRd \[Arm F, F1\] or JNJ-79635322-DRd \[Arm G\] . Enrollment will be staggered with Arm A opening first. Induction therapy (except Arms D and G) is followed by HDT and a single ASCT according to local SoC. Participants will receive maintenance treatment with Tec-D \[Arm A, A1, B, E. F\] or Tal-D \[E1, F1\] or JNJ-79635322-D \[Arm G\]. Arm C, C1 and C2 participants will enter the study at Maintenance Treatment with Tec-D or Tal-DR after induction, HDT, and ASCT according to local SoC (outside of the study). All Arms receive maintenance treatment for a max. of 18 cycles or until confirmed PD, death, intolerable toxicity, loss to follow-up, or consent withdrawal, whichever comes first. An optional EoT is possible for those patients who have sustained MRD negativity of 12 months. Periodic safety evaluations will be conducted to ensure that treatment is safe and tolerable.

Study Record Dates

• First Submitted: November 30, 2022
• First Posted: January 25, 2023
• Study Start: December 1, 2022
• Primary Completion (Estimated): September 15, 2028
• Study Completion (Estimated): September 15, 2029
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (11)