Bispecific T-cell Redirectors as Part of First Line Treatment in Transplant Eligible Multiple Myeloma Patients

NCT06505369 | Recruiting Phase 2

• 1 other identifier: CT number 2023-508212-38-00
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 7

Brief Summary

This is Phase 2, open-label, multicentre, non-randomised study evaluating participants with newly diagnosed MM eligible for high-dose therapy. The goal of the study is to determine if consolidation with T-cell redirectors - Talquetamab and Teclistamab in sequence will improve the response depth: increase MRD negative CR rate.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Transplant Eligible; Talquetamab; Teclistamab; MRD negativity

Outcome Measures

Primary Outcomes (2)

• Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission rate by next generation sequencing ( NGS) after completing consolidation with talquetamab and teclistamab.

  MRD measured by NGS with a sensitivity level of 10-6.

  18 months approximately

• Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission rate by Fluorodeoxyglucose Positron Emission Tomography-Computerized Tomography (FDG PET-CT) scan after completing consolidation with talquetamab and teclistamab.

  MRD assessed by FDG PET-CT scan using Deauville score.

  18 months approximately

Secondary Outcomes (16)

• Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission rate by next generation sequencing ( NGS) after completing induction treatment with Daratumumab-VRd

  6 months approximately

• Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission rate by Fluorodeoxyglucose Positron Emission Tomography-Computerized Tomography (FDG PET-CT) scan after completing induction treatment with Daratumumab-VRd.

  6 months approximately

• Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission conversion by next generation sequencing ( NGS) after completing consolidation treatment with talquetamab.

  12 months approximately

• Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission conversion by Fluorodeoxyglucose Positron Emission Tomography-Computerized Tomography (FDG PET-CT) scan after completing consolidation treatment with talquetamab.

  12 months approximately

• Evaluate efficacy in terms of Minimal Residual Disease (MRD) negative Complete Remission conversion by next generation sequencing ( NGS) after completing consolidation treatment with teclistamab.

  18 months approximately

Other Outcomes (1)

• To capture specific proteomic signatures from MRD positive and negative patients by mass-spectrometry based proteomic profiling.

  42 months approximately

Study Arms (1)

Induction with Dara -VRd + Consolidation with Talquetamab and Teclistamab as monotherapy in sequence

EXPERIMENTAL

Induction with Daratumumab-VRd; Consolidation part I with Talquetamab; Consolidation part II with Teclistamab.

Drug: Daratumumab; Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Talquetamab; Drug: Teclistamab

Interventions

Daratumumab DRUG

Daratumumab will be administered by SC injection

Also known as: JNJ-54767414

Induction with Dara -VRd + Consolidation with Talquetamab and Teclistamab as monotherapy in sequence

Bortezomib DRUG

Bortezomib will be administered by SC injection

Also known as: EU Substance number SUB20020

Induction with Dara -VRd + Consolidation with Talquetamab and Teclistamab as monotherapy in sequence

Lenalidomide DRUG

Lenalidomide will be administered by oral route

Also known as: EU Substance number SUB25389

Induction with Dara -VRd + Consolidation with Talquetamab and Teclistamab as monotherapy in sequence

Dexamethasone DRUG

Dexamethasone will be administered by oral route

Also known as: EU Substance number SUB07017MIG

Induction with Dara -VRd + Consolidation with Talquetamab and Teclistamab as monotherapy in sequence

Talquetamab DRUG

Talquetamab will be administered by SC injection

Also known as: JNJ-64407564

Induction with Dara -VRd + Consolidation with Talquetamab and Teclistamab as monotherapy in sequence

Teclistamab DRUG

Teclistamab will be administered by SC injection

Also known as: JNJ-64007957

Induction with Dara -VRd + Consolidation with Talquetamab and Teclistamab as monotherapy in sequence

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must have documented MM satisfying the IMWG criteria.
• Newly diagnosed patients eligible for high dose therapy and ASCT.
• ECOG performance status score ≤2.
• HIV-positive participants are eligible if they meet all of the following
• No detectable viral load (ie, \<50 copies/mL) at screening
• CD4+ count \>300 cells/mm3 at screening
• No AIDS-defining opportunistic infection within 6 months of screening
• Receiving HAART. Any changes in HAART due to resistance/progression should occur at least 3 months prior to screening. A change in HAART due to toxicity is allowed up to 4 weeks prior to screening.
• Must sign an ICF indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
• Willing and able to adhere to the lifestyle restrictions specified in this protocol.
• A female participant of childbearing potential must have a negative highly sensitive serum (β hCG) pregnancy test at screening
• A female participant must be
• Not of childbearing potential or
• Of childbearing potential and practicing true abstinence; or have a sole partner who is vasectomized; or practicing 2 effective methods of contraception
• A female participant must agree not to donate eggs or freeze for future use during the study and for 6 months after receiving the last dose of study treatment.

You may not qualify if:

• Waldenström's macroglobulinemia, POEMS syndrome, or primary amyloid light chain amyloidosis.
• Known active CNS involvement or exhibits clinical signs of meningeal involvement of MM. If either is suspected, negative whole brain MRI and lumbar cytology are required.
• Peripheral neuropathy or neuropathic pain Grade 2 or higher
• Excluded for any of the following:
• Any ongoing myelodysplastic syndrome or B cell malignancy (other than MM).
• Any history of malignancy, other than MM, which is considered at high risk of recurrence requiring systemic therapy.
• Any active malignancy (ie, progressing or requiring treatment change in the last 24 months) other than MM. The only allowed exceptions are malignancies treated within the last 24 months that are considered cured:
• Non-muscle invasive bladder cancer (solitary Ta-PUN-LMP or low grade, \<3 cm, no CIS).
• Non-melanoma skin cancers treated with curative therapy or localized melanoma treated with curative surgical resection alone.
• Non-invasive cervical cancer.
• Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ or history of localized breast cancer (anti-hormonal therapy is permitted).
• Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally only (RP/RT/focal treatment).
• Other malignancy that is considered cured with minimal risk of recurrence in consultation with the sponsor's medical monitor.
• Stroke within 6 months prior to signing ICF.
• Presence of the following cardiac conditions:

Sponsors & Collaborators

• North Estonia Medical Centre: lead
• Janssen Pharmaceutica: collaborator

Study Sites (7)

Copenhagen University Hospital (Rigshospitalet)

Copenhagen, 2100, Denmark

NOT YET RECRUITING

Odense University Hospital

Odense, 5000, Denmark

NOT YET RECRUITING

Vejle hospital

Vejle, 7100, Denmark

NOT YET RECRUITING

North Estonia Medical Centre

Tallinn, 13419, Estonia

RECRUITING

Oslo University Hospital, Oslo Myeloma Centre

Oslo, 0450, Norway

NOT YET RECRUITING

Stavanger University Hospital

Stavanger, 4068, Norway

NOT YET RECRUITING

St. Olavs Hospital

Trondheim, 7030, Norway

NOT YET RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Bortezomib; Lenalidomide; Dexamethasone; talquetamab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Diana Loigom, MD

  North Estonia Medical Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Diana Loigom, MD

CONTACT

+372 6172173; diana.loigom@regionaalhaigla.ee

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2024
• First Posted: July 17, 2024
• Study Start: June 19, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): October 1, 2028
• Last Updated: July 17, 2024

Record last verified: 2024-07

Locations

NO (3); ES (1); DK (3)