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

Sponsor

University of Heidelberg Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05695508

Collaborator

Janssen Research & Development, LLC (Industry), Deutsche Studiengruppe Multiples Myelom (DSMM) (Other)

Enrollment

Locations

Arms

53.4

Anticipated Duration (Months)

5.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase 2 Study to Evaluate Safety and Efficacy of Teclistamab in Combination with Daratumumab, Lenalidomide, and Dexamethasone with or without Bortezomib as Induction Therapy and Teclistamab in Combination with Daratumumab and Lenalidomide as Maintenance Therapy in Participants with Newly Diagnosed Transplant Eligible Multiple Myeloma.

OBJECTIVES:

The primary objective is to evaluate the safety and tolerability of Tec-DRd and Tec-DVRd as induction therapy and Tec-DR as post-transplant maintenance therapy in participants with ND-TEMM.

The key secondary objective is to evaluate the efficacy of Tec-DRd and Tec-DVRd as induction therapy and Tec-DR as post-transplant maintenance therapy.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Teclistamab (Tec) Drug: Daratumumab Drug: Dexamethasone Drug: Lenalidomide Drug: Bortezomib	Phase 2

Detailed Description

OVERALL DESIGN:

50 participants will be enrolled with approximately 30 participants in Arm A and Arm B combined and 20 participants in Arm C.

Arms A and B will receive Induction Therapy of 6 cycles (28-days each):

Treatment: Tec-DRd (Arm A) or Tec-DVRd (Arm B) followed by HDT and a single ASCT according to local SoC treatment. Thereafter a Maintenance Therapy of 18 cycles with Tec-DR is performed.

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

Participants will receive maintenance treatment with Tec-DR for a maximum of 18 cycles or until confirmed progressive disease, death, intolerable toxicity, loss to follow-up, or consent withdrawal, whichever comes first. 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Induction Treatment of Arm A and B contains 6 cycles of Tec-DRd [Arm A] or Tec-DVRd [Arm B]) Enrollment will be staggered with Arm A opening first and the opening of Arm B dependent on safety results from Arm A. Induction therapy is followed by HDT and a single ASCT according to local SoC. After ASCT, participants will receive maintenance treatment with Tec-DR. Arm C participants will enter the study at Maintenance Treatment with Tec-DR after induction, HDT, and ASCT according to local SoC (outside of the study). Arm A, B and C will receive maintenance treatment for a maximum of 18 cycles or until confirmed progressive disease, death, intolerable toxicity, loss to follow-up, or consent withdrawal, whichever comes first. Periodic safety evaluations will be conducted to ensure that treatment is safe and tolerable.Induction Treatment of Arm A and B contains 6 cycles of Tec-DRd [Arm A] or Tec-DVRd [Arm B]) Enrollment will be staggered with Arm A opening first and the opening of Arm B dependent on safety results from Arm A. Induction therapy is followed by HDT and a single ASCT according to local SoC. After ASCT, participants will receive maintenance treatment with Tec-DR. Arm C participants will enter the study at Maintenance Treatment with Tec-DR after induction, HDT, and ASCT according to local SoC (outside of the study). Arm A, B and C will receive maintenance treatment for a maximum of 18 cycles or until confirmed progressive disease, death, intolerable toxicity, loss to follow-up, or consent withdrawal, whichever comes first. Periodic safety evaluations will be conducted to ensure that treatment is safe and tolerable.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Study to Evaluate Safety and Efficacy of Teclistamab in Combination With Daratumumab, Lenalidomide, and Dexamethasone With or Without Bortezomib as Induction Therapy and Teclistamab in Combination With Daratumumab and Lenalidomide as Maintenance Therapy in Participants With Newly Diagnosed Transplant Eligible Multiple Myeloma

Actual Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

May 15, 2026

Anticipated Study Completion Date :

May 15, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Tec-DRd Induction and Tec-DR 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 and lenalidomide in 18 cycles of maintenance therapy.	Drug: Teclistamab (Tec) Subcutaneous administration of Teclistamab Other Names: JNJ-64007957 Drug: Daratumumab Subcutaneous administration of Daratumumab Drug: Dexamethasone administered i.v. or orally Drug: Lenalidomide Administration oral
Experimental: Arm B Tec-DVRd Induction and Tec-DR 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 and lenalidomide in 18 cycles of maintenance therapy.	Drug: Teclistamab (Tec) Subcutaneous administration of Teclistamab Other Names: JNJ-64007957 Drug: Daratumumab Subcutaneous administration of Daratumumab Drug: Dexamethasone administered i.v. or orally Drug: Lenalidomide Administration oral Drug: Bortezomib Subcutaneous administration
Experimental: Arm C Tec-DR Maintenance Arm C participants will receive 18 cycles of teclistamab SC injection in combination with daratumumab SC and lenalidomide as maintenance therapy.	Drug: Teclistamab (Tec) Subcutaneous administration of Teclistamab Other Names: JNJ-64007957 Drug: Daratumumab Subcutaneous administration of Daratumumab Drug: Lenalidomide Administration oral

Arm

Intervention/Treatment

Experimental: Arm A Tec-DRd Induction and Tec-DR 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 and lenalidomide in 18 cycles of maintenance therapy.

Drug: Teclistamab (Tec)

Subcutaneous administration of Teclistamab

Other Names:

JNJ-64007957

Drug: Daratumumab

Subcutaneous administration of Daratumumab

Drug: Dexamethasone

administered i.v. or orally

Drug: Lenalidomide

Administration oral

Experimental: Arm B Tec-DVRd Induction and Tec-DR 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 and lenalidomide in 18 cycles of maintenance therapy.

Drug: Teclistamab (Tec)

Subcutaneous administration of Teclistamab

Other Names:

JNJ-64007957

Drug: Daratumumab

Subcutaneous administration of Daratumumab

Drug: Dexamethasone

administered i.v. or orally

Drug: Lenalidomide

Administration oral

Drug: Bortezomib

Subcutaneous administration

Experimental: Arm C Tec-DR Maintenance

Arm C participants will receive 18 cycles of teclistamab SC injection in combination with daratumumab SC and lenalidomide as maintenance therapy.

Drug: Teclistamab (Tec)

Subcutaneous administration of Teclistamab

Other Names:

JNJ-64007957

Drug: Daratumumab

Subcutaneous administration of Daratumumab

Drug: Lenalidomide

Administration oral

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] [monthly during induction and maintenance]
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 and daratumumab [pharmacokinetics] [through study completion, up to 28 months]
Presence of ADAs to teclistamab 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

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 Arm A and Arm B 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.

Participants Arm C 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 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 at the time of enrollment.

In addition, for participants treated with consolidation therapy, the participant must be within 3 months of the last dose of consolidation therapy 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.
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 90 days after the last dose of any study treatment regimen.
Plans to father a child while enrolled in this study or within 90 days after the last dose of any component of the study treatment regimen.

Arm A and B - 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

Arm C

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 ≥140 mg of prednisone 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

Locations

	Site	City	Country	Postal Code
1	Charité University Medicin Berlin	Berlin	Germany	12203
2	Clinic Chemnitz	Chemnitz	Germany	09113
3	University Clinic Technical University Dresden	Dresden	Germany	01307
4	University Clinic Freiburg	Freiburg	Germany	79106
5	Asklepios Clinic Hamburg Altona	Hamburg	Germany	22763
6	University Hospital Heidelberg	Heidelberg	Germany	69120
7	University Clinic Schleswig-Holstein Campus Kiel	Kiel	Germany	24105
8	Technical University Munich	Munich	Germany	81675
9	University Würzburg	Würzburg	Germany