GMMG-HD10 / DSMM-XX / 64007957MMY2003, MajesTEC-5
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT05695508
- Lead Sponsor
- University of Heidelberg Medical Center
- Brief Summary
Phase 2 Study to Evaluate Safety and Efficacy of Teclistamab- and Talquetamab-based Combination Regimens in Participants with Newly Diagnosed Transplant Eligible Multiple Myeloma
OBJECTIVES:
The primary objective is to evaluate the safety and tolerability of teclistamab- and talquetamab-based combination regimens over the entire treatment phase for each arm, in participants with ND-TEMM
The key secondary objective is to evaluate the efficacy of teclistamab- and talquetamab-based combination regimens as induction and post-transplant maintenance treatments, and teclistamab in combination with talquetamab as replacement for HDT+ASCT following induction
- Detailed Description
OVERALL DESIGN:
130 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 F1. 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 Tec-DVRd induction followed by 18 cycles Tec-Tal. No HDT ASCT will be performed in Arm D.
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) 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 130
- 18 years of age to 70 years of age, inclusive
- Have an ECOG performance status score of 0 to 2 at screening
- Have clinical laboratory values meeting prespecified criteria during the Screening Phase.
Participants in Arms A, A1, B, D, E, E1, F and F1 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
-
Urine M-protein level ≥200 mg/24 hours or
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Serum immunoglobulin free light chain level ≥10 mg/dL and abnormal serum free light chain ratio
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Newly diagnosed participants for whom HDT and ASCT is part of the intended treatment plan (except Arm D 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 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 without evidence of progression at the time of enrollment.
- 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.
-
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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.
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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.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm E1 Tal-DRd Induction and Tal-D Maintenance Talquetamab 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. Arm F Tal-DVRd Induction and Tec-D Maintenance Talquetamab 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. Arm D Tec-DRd Induction and Tec-Tal following induction Talquetamab 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. Arm E Tal-DRd Induction and Tec-D Maintenance Talquetamab 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. Arm B Tec-DVRd Induction and Tec-D Maintenance Teclistamab (Tec) 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. Arm C Tec-D Maintenance Teclistamab (Tec) Arm C participants will receive maximum 18 cycles of teclistamab SC injection in combination with daratumumab SC and lenalidomide as maintenance therapy. Arm A1 Tec-DRd Induction and Tec-D Maintenance Teclistamab (Tec) 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. Arm C2 Tal-DR Maintenance Daratumumab Arm C2 participants will receive maximum 18 cycles of talquetamab SC injection in combination with daratumumab SC and lenalidomide as maintenance therapy. Arm C2 Tal-DR Maintenance Lenalidomide Arm C2 participants will receive maximum 18 cycles of talquetamab SC injection in combination with daratumumab SC and lenalidomide as maintenance therapy. Arm C2 Tal-DR Maintenance Talquetamab Arm C2 participants will receive maximum 18 cycles of talquetamab SC injection in combination with daratumumab SC and lenalidomide as maintenance therapy. Arm A1 Tec-DRd Induction and Tec-D Maintenance Lenalidomide 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. Arm A Tec-DRd Induction and Tec-D Maintenance Teclistamab (Tec) 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. Arm A Tec-DRd Induction and Tec-D Maintenance Daratumumab 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. Arm A Tec-DRd Induction and Tec-D Maintenance Dexamethasone 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. Arm A Tec-DRd Induction and Tec-D Maintenance Lenalidomide 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. Arm B Tec-DVRd Induction and Tec-D Maintenance Daratumumab 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. Arm B Tec-DVRd Induction and Tec-D Maintenance Dexamethasone 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. Arm B Tec-DVRd Induction and Tec-D Maintenance Lenalidomide 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. Arm B Tec-DVRd Induction and Tec-D Maintenance Bortezomib 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. Arm C Tec-D Maintenance Daratumumab Arm C participants will receive maximum 18 cycles of teclistamab SC injection in combination with daratumumab SC and lenalidomide as maintenance therapy. Arm A1 Tec-DRd Induction and Tec-D Maintenance Daratumumab 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. Arm A1 Tec-DRd Induction and Tec-D Maintenance Dexamethasone 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. Arm D Tec-DRd Induction and Tec-Tal following induction Teclistamab (Tec) 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. Arm D Tec-DRd Induction and Tec-Tal following induction Daratumumab 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. Arm D Tec-DRd Induction and Tec-Tal following induction Dexamethasone 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. Arm D Tec-DRd Induction and Tec-Tal following induction Lenalidomide 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. Arm E Tal-DRd Induction and Tec-D Maintenance Teclistamab (Tec) 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. Arm E Tal-DRd Induction and Tec-D Maintenance Daratumumab 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. Arm E Tal-DRd Induction and Tec-D Maintenance Dexamethasone 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. Arm E Tal-DRd Induction and Tec-D Maintenance Lenalidomide 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. Arm E1 Tal-DRd Induction and Tal-D Maintenance Daratumumab 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. Arm E1 Tal-DRd Induction and Tal-D Maintenance Dexamethasone 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. Arm E1 Tal-DRd Induction and Tal-D Maintenance Lenalidomide 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. Arm F Tal-DVRd Induction and Tec-D Maintenance Teclistamab (Tec) 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. Arm F Tal-DVRd Induction and Tec-D Maintenance Daratumumab 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. Arm F Tal-DVRd Induction and Tec-D Maintenance Dexamethasone 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. Arm F Tal-DVRd Induction and Tec-D Maintenance Lenalidomide 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. Arm F Tal-DVRd Induction and Tec-D Maintenance Bortezomib 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. Arm F1 Tal-DVRd Induction and Tal-D Maintenance Daratumumab 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. Arm F1 Tal-DVRd Induction and Tal-D Maintenance Dexamethasone 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. Arm F1 Tal-DVRd Induction and Tal-D Maintenance Lenalidomide 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. Arm F1 Tal-DVRd Induction and Tal-D Maintenance Bortezomib 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. Arm F1 Tal-DVRd Induction and Tal-D Maintenance Talquetamab 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.
- Primary Outcome Measures
Name Time Method number of incidence and severity of adverse events [safety and tolerability] through study completion, up to 28 months
- Secondary Outcome Measures
Name Time Method 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) MRD negativity rate measured by Flow Cytometry
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) 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)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 Stem cell yield after High Dose Therapy (after app. 10 months) feasibility of successful transplantation
days to engraftment after High Dose Therapy (after app. 10 months) feasibility of successful transplantation
Trial Locations
- Locations (11)
Charité University Medicin Berlin
🇩🇪Berlin, Germany
Clinic Chemnitz gGmbH
🇩🇪Chemnitz, Germany
University Clinic Technical University Dresden
🇩🇪Dresden, Germany
University Clinic Düsseldorf
🇩🇪Düsseldorf, Germany
University Clinic Freiburg
🇩🇪Freiburg, Germany
Hamburg University Clinic Eppendorf
🇩🇪Hamburg, Germany
Asklepios Clinic Hamburg Altona
🇩🇪Hamburg, Germany
University Hospital Heidelberg
🇩🇪Heidelberg, Germany
University Clinic Schleswig-Holstein Campus Kiel
🇩🇪Kiel, Germany
Technical University Munich
🇩🇪Munich, Germany
University Würzburg
🇩🇪Würzburg, Germany