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

Universitaetsklinikum Heidelberg AöR11 sites in 1 country130 target enrollmentSeptember 11, 2024

DrugsLenalidomid HEXAL 10 mg Hartkapseln DEXAMETHASONE teclistamab Lenalidomid HEXAL 25 mg Hartkapseln BETAMETHASONE DISODIUM PHOSPHATE teclistamab, teclistamab JNJ-64407564, JNJ-64407564 VELCADE 3.5 mg powder for solution for injection DARZALEX 1800 mg solution for injection JNJ-64407564 Lenalidomid HEXAL 5 mg Hartkapseln CDC-501 CC-5013 3-(4'aminoisoindoline-1'-one)-1-piperidine-2,6-dione Lenalidomid HEXAL 5 mg Hartkapseln, Lenalidomid HEXAL 15 mg Hartkapseln, Lenalidomid HEXAL 10 mg Hartkapseln, Lenalidomid HEXAL 25 mg Hartkapseln SYP-1512 Lenalidomid HEXAL 15 mg Hartkapseln 3-(7-AMINO-3-OXO-1H-ISOINDOL-2-YL)PIPERIDINE-2,6-DIONE

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Not specified
Sponsor: Universitaetsklinikum Heidelberg AöR
Enrollment: 130
Locations: 11
Primary Endpoint: Incidence and severity of AEs and SAEs
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

To evaluate the safety and tolerability of teclistamab- and talquetamabbased combination regimens over the entire treatment phase for each arm, in participants with ND-TEMM.

Registry

euclinicaltrials.eu

Start Date

September 11, 2024

End Date

TBD

Last Updated

last year

Study Type

Interventional clinical trial of medicinal product

Investigators

Sponsor

Universitaetsklinikum Heidelberg AöR

Responsible Party

Principal Investigator

GMMG Studiensekretariat

Scientific

Universitaetsklinikum Heidelberg AöR

Eligibility Criteria

Inclusion Criteria

•18 to 70 years of age, inclusive
•Must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
•Participants in Arms A, A1, B, D, E, E1, F, F1 must also satisfy all of the following criteria to be enrolled in the study: 1A. Documented multiple myeloma as defined by the criteria below: a. Multiple myeloma diagnosis according to the IMWG diagnostic criteria b. 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 immunoglobulin kappa lambda free light chain ratio 2A. Newly diagnosed participants for whom HDT and ASCT is part of the intended treatment plan.
•Participants Arms C, C1; C2 must also satisfy all of the following criteria 1B. diagnosed multiple myeloma according to IMWG criteria, see note
•2B. 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
•3B. 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.
•4B. 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

•1.a. Ongoing myelodysplastic syndrome or B-cell malignancy (other than MM)
•Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug/excipients.
•Pregnant, breastfeeding, or planning pregnancy while enrolled in this study or within 6 months after the last dose of any study treatment.
•Plans to father a child while enrolled in this study or within 100 days after the last dose of any study treatment.
•significant traumatic injury or major surgery within 2 weeks prior to the start of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the study or within 2 weeks after the last dose of study treatment.
•Received an investigational drug, used an invasive investigational medical device within 4 weeks or 5 half-lives of the respective drug/IMP before enrollment or is enrolled in an interventional study.
•Have gastrointestinal disease that may significantly alter the absorption of oral drugs
•Received a live, attenuated vaccine within 4 weeks before the first dose of study treatment.
•Be unable or unwilling to undergo antithrombotic prophylactic treatment.
•Arms A, A1, B. D, E, E1, F and F1

Outcomes

Primary Outcomes

Incidence and severity of AEs and SAEs

Secondary Outcomes

To evaluate MRD negativity rates, conversion, and sustainability: Post-induction, post-ASCT, post-maintenance, and best overall - MRD negative CR Sustained MRD negative CR (duration ≥12 months) after 18 cycles of maintenance treatment MRD negative CR conversion and deepening during maintenance
To evaluate the efficacy of Teclistamab and Talquetamab based combination regimes as induction and posttransplant maintenance treatments, and teclistamab in combination with talquetamab as replacement for ASCT following induction. Post-induction, post-ASCT (Arms A, A1, B, E, E1 and, if applicable, F and F1), postmaintenance (Arms A, A1, B, E, E1 and, ifapplicable, F and F1), post-Tec-Tal (Arm D), and best overall: - ORR (at least a PR or better) - CR or better - VGPR or better DOR PFS
To assess feasibility of successful transplantation (all arms except ArmD): Stem cell yield and days to engraftment (all arms except Arm D)
To characterize the PK of teclistamab and talquetamab in participants with multiple myeloma before and after an ASCT or during Tec-Tal treatment, and to characterize the PK of daratumumab after an ASCT: PK parameters using population PK approach
To assess the immunogenicity of teclistamab, talquetamab and daratumumab: Measure presence of ADAs
evaluation of this end points: MRD negativity rates, conversion, and sustainability: Post-induction, post-ASCT, post-maintenance, and best overall Sustained MRD negative CR: ≥12 months and after 18 cycles of maintenance treatment. Sustained MRD negative CR - ORR (at least a PR or better) - CR or better - VGPR or better Post-induction, post-ASCT, post-maintenance (assessments 3-monthly), and best overall:
of evaluation of this end points (continued) DOR: 3-monthly response assessment PFS: 3-monthly response assessment PK analysis: over the