Teclistamab-Daratumumab and Talquestamab-Daratumumab in Newly Diagnosed High-risk Multiple Myeloma

NCT05849610 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: GEM-TECTAL
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 10

Brief Summary

The goal of this Phase 2, open-label, multicenter, non-randomized pilot study is to evaluate the efficacy (in terms of MRD negative CR rate after Intensification therapy) and safety of Tec-Dara (Teclistamab+Daratumumab) and Tal-Dara (Talquetamab+Daratumumab) in de novo high-risk multiple myeloma (DNHRMM) patients.

Conditions

High-Risk de Novo Multiple Myeloma

Keywords

High-Risk de novo Multiple Myeloma; Teclistamab; Talquetamab; Daratumumab

Outcome Measures

Primary Outcomes (2)

• Evaluate efficacy in terms of Measurable Residual Disease (MRD) negative Complete Remission rate by Next Generation Flow Cytometry after Teclistamab plus Daratumumab intensification.

  MRD measured by Next Generation Flow Cytometry (NGF, with a sensitivity level of 10-6) after 6 cycles of Tec-Dara therapy.

  22 months approximately

• Evaluate efficacy in terms of Measurable Residual Disease (MRD) negative Complete Remission rate by Fluorodeoxyglucose Positron Emission Tomography-Computerized Tomography (FDG PET-CT) scan using the Deauville score, after Tec-Dara intensification.

  MRD measured by Fluorodeoxyglucose Positron Emission Tomography-Computerized Tomography (FDG PET-CT) scan.

  22 months approximately

Secondary Outcomes (13)

• To evaluate MRD negative CR rate after Daratumumab plus bortezomib, lenalidomide and dexamethasone (D-VRD) induction.

  16 months approximately

• To evaluate MRD negativity after Teclistamab plus Daratumumab (Tec-Dara) intensification using alternative methods

  22 months approximately

• To evaluate MRD conversion after early rescue intervention with Talqutamab plus Daratumumab (Tal-Dara)

  4 years approximately

• To evaluate MRD conversion after Tec-Dara intensification

  22 months approximately

• To evaluate sustained MRD negativity during maintenance treatment in both Tec-Dara and Tal-Dara treatment arms

  76 months approximately

Study Arms (1)

Induction VRD-Dara + Intensification Tec-Dara + Maintenance Tec-Dara + ERI Tal-Dara

EXPERIMENTAL

Induction (4 cycles) D-VRD. After Induction, all patients recieve 1st INTENSIFICATION treatment (6 cycles of Tec-Dara). Cycles will be of 28 days (4-week cycles) in duration for daratumumab and for Teclistamab. At the end of 1st Intensification timepoint treatments depends on MRD status: 1. MRD negative patients in CR at the end of Intensification will receive MAINTENANCE therapy with Tec-Dara continuously for 2 years. Crossover: patients who convert MRD positive or relapse from CR any time during Teclistamab maintenance will receive the same treatment as MRD positive individuals (early rescue intervention, ERI). 2. MRD positive patients or patients who didn't achieve CR despite MRD negativity, will have ERI (Tal-Dara 6 cycles). MRD and response will be evaluated again after 6 cycles treatment with Tal-Dara. MRD negative patients in CR will receive continuous treatment with Tal-Dara for 2 years.

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

Interventions

Daratumumab DRUG

Daratumumab will be administered by SC injection.

Induction VRD-Dara + Intensification Tec-Dara + Maintenance Tec-Dara + ERI Tal-Dara

Bortezomib DRUG

Bortezomib dose will be calculated using the patient's actual body surface area (BSA) at baseline and will be administered by subcutaneous (SC) injection.

Induction VRD-Dara + Intensification Tec-Dara + Maintenance Tec-Dara + ERI Tal-Dara

Lenalidomide DRUG

Lenalidomide will be administered by oral route.

Induction VRD-Dara + Intensification Tec-Dara + Maintenance Tec-Dara + ERI Tal-Dara

Teclistamab DRUG

Teclistamab will be administered by SC injection.

Also known as: JNJ-64007957

Induction VRD-Dara + Intensification Tec-Dara + Maintenance Tec-Dara + ERI Tal-Dara

Talquetamab DRUG

Talquetamab will be administered by subcutaneous (SC) injection.

Also known as: JNJ-64407564

Induction VRD-Dara + Intensification Tec-Dara + Maintenance Tec-Dara + ERI Tal-Dara

Eligibility Criteria

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

You may qualify if:

• Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
• Patient has given voluntary written informed consent before performance of any study-related procedure nor part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
• Patient is ≥ 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
• Patient has documented diagnosis of multiple myeloma according to IMWG diagnostic criteria, with at least one of the following high-risk features:
• High-risk FISH: del(17p), t(4;14), t(14;16) and 1q amplifications.
• R-ISS 3
• Presence of extramedullary disease, defined as presence of paramedullary lesions or extramedullary plasmacytoma.
• Note: In order to have a representative population with high-risk features, 50% of patients included will have ultra-high risk disease defined as: i) R-ISS 3; ii) Double hit (at least two high-risk cytogenetic abnormalities); iii) One high-risk cytogenetic abnormality + extramedullary disease.
• Patients eligible for transplant with age ≤ 70 years old (young and transplant-eligible) or patients not eligible for transplant with ECOG-PS modified frailty score of 0-1 (elderly-fit).
• Patient has an ECOG performance status of 0, 1or 2.

You may not qualify if:

• Prior or current systemic therapy or SCT for any plasma cell dyscrasia, with the exception of 1 cycle of antimyeloma treatment or the emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment while waiting for results of genetic analysis. A cycle of therapy may include treatment with proteasome inhibitors, immunomodulatory drugs, alkylators and corticosteroids, and/or anti-CD38 monoclonal antibodies (i.e, bortezomib-thalidomide-dexamethasone, D-VTD, bortezomib-lenalidomide-dexamethasone, or bortezomib-cyclophosphamide-dexamethasone, are valid options).
• Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the NCI-CTCAE Version 5.
• Patient has a diagnosis of primary light chain amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell leukemia or active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) at the time of screening.
• Myelodysplastic syndrome or active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than relapsed/refractory multiple myeloma. The only allowed exceptions are malignancies treated within the last 24 months that are considered completely cured:
• Non-muscle invasive bladder cancer (solitary Ta-papillary urothelial neoplasm of low malignancy or low grade, \< 3 cm, no carcinoma in situ).
• Skin cancer (non-melanoma skin cancers treated with curative therapy or localized melanoma treated with curative surgical resection alone).
• Noninvasive cervical cancer.
• Localized prostate cancer (M0, N0) with a Gleason score of ≤ 7a, treated locally only (radical prostatectomy/radiation therapy/focal treatment).
• Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, localized breast cancer and receiving antihormonal agents.
• Other malignancy that is considered cured with minimal risk of recurrence.
• Patient has CNS or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology are required.

Sponsors & Collaborators

• PETHEMA Foundation: lead
• Janssen Pharmaceutica N.V., Belgium: collaborator

Study Sites (10)

Hospital Germans Trials i Pujol

Badalona, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain

Location

Hospital Doce de Octubre

Madrid, 28041, Spain

Location

Hospital Virgen de la Arrixaca

Murcia, Spain

Location

Clinica Universidad de Navarra

Pamplona, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

H. Universitario Marqués de Valdecilla

Santander, Spain

Location

Complejo Hospitalario Santiago (CHUS)

Santiago de Compostela, Spain

Location

Hospital Vírgen del Rocío

Seville, Spain

Location

Hospital Universitari i Politecnic la Fe

Valencia, Spain

Location

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  BACKGROUND

MeSH Terms

Interventions

daratumumab; Bortezomib; Lenalidomide; talquetamab

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

Study Officials

• Juan José Lahuerta Palacios, Dr

  Hospital Universitario 12 de Octubre

  STUDY CHAIR

• Joan Bladé, Dr

  Hospital Clinic of Barcelona

  STUDY CHAIR

• Mª Victoria Mateos, Dr

  Hospital Clínico Universitario de Salamanca

  STUDY CHAIR

• Paula Rodríguez Otero, Dr

  Clínica Universidad de Navarra

  STUDY CHAIR

• Jesús San Miguel, Dr

  Clínica Universidad de Navarra

  STUDY CHAIR

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: February 24, 2023
• First Posted: May 9, 2023
• Study Start: September 21, 2023
• Primary Completion: March 1, 2025
• Study Completion (Estimated): July 1, 2029
• Last Updated: March 19, 2025

Record last verified: 2025-03

Locations

ES (10)