GMMG-HD10 / DSMM-XX / 64007957MMY2003, MajesTEC-5 Clinical Trial Results and Information

A Phase 2 Study to Evaluate Safety and Efficacy of Teclistamab- and Talquetamab-based Combination Regimens in Participants with Newly Diagnosed Transplant Eligible Multiple Myeloma

ClinicalTrials.gov processed this data on October 20, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

RECRUITING (See Contacts and Locations)
Verified October 2024 by University of Heidelberg Medical Center, Janssen Research & Development, LLC, Deutsche Studiengruppe Multiples Myelom (DSMM)

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 30, 2022
First Posted: January 25, 2023
Last Update Posted: October 23, 2024
Last Verified: October 2024
History of Changes

Disclaimer

Listing a study on this site does not mean it has been evaluated by the U.S. Federal Government. The safety and scientific validity of a study listed on ClinicalTrials.gov is the responsibility of the study sponsor and investigators. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating.

ClinicalTrials.gov, a resource provided by the U.S. National Library of Medicine (NLM), is a registry and results information database of clinical research studies sponsored or funded by a broad range of public and private organizations around the world. Not all studies listed on ClinicalTrials.gov are funded by the National Institutes of Health (NIH) or other agencies of the U.S. Federal Government. Not all listed studies are regulated and/or reviewed by the U.S. Food and Drug Administration or other governmental entities.

Information on ClinicalTrials.gov is provided by study sponsors and investigators, and they are responsible for ensuring that the studies follow all applicable laws and regulations. NLM staff do not verify the scientific validity or relevance of the submitted information beyond a limited quality control review for apparent errors, deficiencies, or inconsistencies.

Choosing to participate in a study is an important personal decision. Before you participate in a study, discuss all options with your health care provider and other trusted advisors. For more information about participating in clinical studies, see Learn About Clinical Studies, which includes questions that you might want to ask before deciding to participate in a study.

For more information about using the information on ClinicalTrials.gov, please also see Terms and Conditions.

See also the Web Policies and Notices for the NIH web site.

Study 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.

Condition or Disease	Intervention/Treatment
Multiple Myeloma	Drug: Teclistamab (Tec) Drug: Daratumumab Drug: Dexamethasone Drug: Lenalidomide Drug: Bortezomib Drug: Talquetamab

Study Design

Study Type	Interventional
Anticipated Enrollment	130 participants
Design Allocation	Non-Randomized
Interventional Model	Parallel Assignment
Masking	None (Open Label)
Primary Purpose	Treatment
Official Title	A Phase 2 Study to Evaluate Safety and Efficacy of Teclistamab- and Talquetamab-based Combination Regimens in Participants with Newly Diagnosed Transplant Eligible Multiple Myeloma
Study Start Date	December 1, 2022
Anticipated Primary Completion Date	February 15, 2027
Anticipated Study Completion Date	August 15, 2028

Groups and Cohorts

Group/ Cohort	Intervention/ 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 Drug: Daratumumab Drug: Dexamethasone Drug: Lenalidomide
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 Drug: Daratumumab Drug: Dexamethasone Drug: Lenalidomide Drug: Bortezomib
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 Drug: Daratumumab
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 Drug: Daratumumab Drug: Dexamethasone Drug: Lenalidomide
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 Drug: Lenalidomide Drug: Talquetamab
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 Drug: Daratumumab Drug: Dexamethasone Drug: Lenalidomide Drug: Talquetamab
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 Drug: Daratumumab Drug: Dexamethasone Drug: Lenalidomide Drug: Talquetamab
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 Drug: Dexamethasone Drug: Lenalidomide Drug: Talquetamab
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 Drug: Daratumumab Drug: Dexamethasone Drug: Lenalidomide Drug: Bortezomib Drug: Talquetamab
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 Drug: Dexamethasone Drug: Lenalidomide Drug: Bortezomib Drug: Talquetamab

Outcome Measures

Primary Outcome Measures

number of incidence and severity of adverse events [safety and tolerability] [through study completion, up to 28 months]

Secondary Outcome Measures

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

Eligibility Criteria

Ages Eligible for Study	18 Years to 70 Years (Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	No
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 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 Serum immunoglobulin free light chain level ≥10 mg/dL and abnormal serum free light chain ratio 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.
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 Collaborators	University of Heidelberg Medical Center, Janssen Research & Development, LLC, Deutsche Studiengruppe Multiples Myelom (DSMM)
	Janssen Research & Development, LLC, Deutsche Studiengruppe Multiples Myelom (DSMM)
Locations	Charité University Medicin Berlin \| Berlin, Germany, 12203 Clinic Chemnitz gGmbH \| Chemnitz, Germany, 09113 University Clinic Technical University Dresden \| Dresden, Germany, 01307 University Clinic Düsseldorf \| Düsseldorf, Germany, 40225 University Clinic Freiburg \| Freiburg, Germany, 79106 Hamburg University Clinic Eppendorf \| Hamburg, Germany, 20246 Asklepios Clinic Hamburg Altona \| Hamburg, Germany, 22763 University Hospital Heidelberg \| Heidelberg, Germany, 69120 University Clinic Schleswig-Holstein Campus Kiel \| Kiel, Germany, 24105 Technical University Munich \| Munich, Germany, 81675 University Würzburg \| Würzburg, Germany,

More Information

Additional Relevant MeSH Terms

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