Combination treatment for newly diagnosed multiple myeloma patients

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

This study is testing a new combination treatment for people with newly diagnosed multiple myeloma to see if it can be a safer and more effective alternative to traditional high-dose therapy and stem cell transplants.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 160 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: University of Heidelberg Medical Center (other)
• Drugs / interventions: Teclistamab, Talquetamab
• Locations: 11 sites (Berlin and 10 other locations)
• Trial ID: NCT05695508 on ClinicalTrials.gov

What this trial studies

This Phase 2 clinical trial evaluates the safety and efficacy of teclistamab- and talquetamab-based combination regimens in participants with newly diagnosed transplant-eligible multiple myeloma. The study involves multiple treatment arms, where participants will receive induction therapy followed by maintenance therapy, with a focus on assessing tolerability and effectiveness. A total of 130 participants will be enrolled, and the study will monitor safety throughout the treatment phases. The trial aims to determine the potential of these therapies to replace traditional high-dose therapy and autologous stem cell transplantation.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with newly diagnosed multiple myeloma requiring treatment and who are eligible for high-dose therapy and autologous stem cell transplantation.

Not a fit: Patients with relapsed or refractory multiple myeloma or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with newly diagnosed multiple myeloma.

How similar studies have performed: Other studies have shown promise with similar combination therapies in treating multiple myeloma, indicating potential for success in this approach.

Eligibility criteria

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 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:

1\. Documented multiple myeloma requiring treatment as defined by the criteria below:

1. Multiple myeloma diagnosis according to the IMWG diagnostic criteria
2. Measurable disease at screening as defined by any of the following:

   1\. 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:
   1. Newly diagnosed multiple myeloma according to IMWG criteria.
   2. 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.

   3 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.

   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.

Where this trial is running

Berlin and 10 other locations

• Charité University Medicin Berlin — Berlin, Germany (RECRUITING)
• Clinic Chemnitz gGmbH — Chemnitz, Germany (RECRUITING)
• University Clinic Technical University Dresden — Dresden, Germany (RECRUITING)
• University Clinic Düsseldorf — Düsseldorf, Germany (RECRUITING)
• University Clinic Freiburg — Freiburg im Breisgau, Germany (RECRUITING)
• Hamburg University Clinic Eppendorf — Hamburg, Germany (RECRUITING)
• Asklepios Clinic Hamburg Altona — Hamburg, Germany (RECRUITING)
• University Hospital Heidelberg — Heidelberg, Germany (RECRUITING)
• University Clinic Schleswig-Holstein Campus Kiel — Kiel, Germany (RECRUITING)
• Technical University Munich — Munich, Germany (RECRUITING)
• University Würzburg — Würzburg, Germany (RECRUITING)

Study contacts

• Study coordinator: Marc S Raab, Prof. Dr. med

Conditions: Multiple Myeloma