MMulti-Immune HR; Multi-Target Immunotherapy for High-Risk Multiple Myeloma

NCT07029776 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 29725064407564MMY201
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research is to learn whether using teclistamab and talquetamab at different time points will improve survival in participants with high-risk Multiple Myeloma (MM). The treatment on this study will consist of Induction chemotherapy and stem cell collection, Immunotherapy 1 chemotherapy and Immunotherapy 2 chemotherapy. For participants whose testing show they are Minimal Residual Disease (MRD) positive (still have myeloma cells present in the bone marrow testing), a Melphalan-based stem cell transplant will be performed. For participants whose testing show they are MRD negative, the stem cell transplant will not be performed. All participants will go on to receive Immunotherapy 3 chemotherapy, Immunotherapy 4 chemotherapy, and Maintenance therapy.

Conditions

Multiple Myeloma (MM)

Keywords

Bispecific Antibodies; High-Risk Newly Diagnosed Multiple Myeloma; Multi-Target Immunotherapy; High-Risk Multiple Myeloma; Teclistamab; Daratumumab

Outcome Measures

Primary Outcomes (2)

• Complete Response Rate (CRR) in subjects with high-risk multiple myeloma (HRMM) treated with the sequential use of Bispecific Antibodies.

  to determine the Complete Response Rate (CRR), defined as the proportion of subjects achieving complete response (CR) or stringent complete response (sCR) according to IMWG criteria at the 'Pre-Maintenance' timepoint (after completion of Immunotherapy #4, Cycle 4)

  Up to 4 years

• the 2-year Progression-Free Survival (PFS) percentage in subjects with high-risk multiple myeloma (HRMM) treated with the sequential use of Bispecific Antibodies.

  determine the 2-year Progression-Free Survival (PFS) percentage in subjects with high-risk multiple myeloma (HRMM) treated with the sequential use of bispecific antibodies.

  2 years after study completion

Secondary Outcomes (1)

• evaluate the Minimal Residual Disease (MRD) Negativity Rate (MRDNR) in subjects with HRMM treated with the sequential use of Bispecific Antibodies.

  Up to 4 years

Study Arms (2)

MRD-negative

EXPERIMENTAL

Subjects who are MRD-negative (a threshold of 10\^5) will be given teclistamab+daratumumab followed by talquetamab+daratumumab each for 4 cycles followed by 2-year fixed duration treatment with daratumumab and lenalidomide extended/maintenance therapy for a maximum of 24 cycles, or until myeloma progression.

Drug: teclistamab+daratumumab followed by talquetamab+daratumumab followed by duration treatment with daratumumab and lenalidomide extended/maintenance

MRD-positive

EXPERIMENTAL

Subjects who are MRD-positive (a threshold of 10\^5) will receive a single melphalan (MEL)-based hematopietic stem cell transplantation (HSCT) followed by teclistamab+daratumumab followed by talquetamab+daratumumab each for 4 cycles followed by a 2-year fixed duration treatment with daratumumab and lenalidomide extended/maintenance therapy for a maximum of 24 cycles, or until myeloma progression. MRD status with classification threshold of 10\^5 will be assessed by standardized flow cytometry.

Procedure: melphalan (MEL)-based hematopietic stem cell transplantation (HSCT) followed by drug therapy

Interventions

melphalan (MEL)-based hematopietic stem cell transplantation (HSCT) followed by drug therapy PROCEDURE

Subjects who are MRD-positive (a threshold of 10\^5) will receive a single melphalan (MEL)-based hematopietic stem cell transplantation (HSCT) followed by teclistamab+daratumumab followed by talquetamab+daratumumab each for 4 cycles followed by a 2-year fixed duration treatment with daratumumab and lenalidomide extended/maintenance therapy for a maximum of 24 cycles, or until myeloma progression.

MRD-positive

teclistamab+daratumumab followed by talquetamab+daratumumab followed by duration treatment with daratumumab and lenalidomide extended/maintenance DRUG

teclistamab+daratumumab followed by talquetamab+daratumumab each for 4 cycles followed by 2-year fixed duration treatment with daratumumab and lenalidomide extended/maintenance therapy for a maximum of 24 cycles, or until myeloma progression.

Also known as: JNJ-64407564, Anti-GPRC5D × CD3 Antibody, Talvey, JNJ-54767414, Darzalex, JNJ-64007957, Tecvayli

MRD-negative

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have newly diagnosed active MM requiring treatment. Patients with a previous history of smoldering myeloma will be eligible if there is evidence of PD requiring initiation of treatment.
• Patients must be either untreated or have not received more than two months of MM therapy. However, bisphosphonates and localized radiation are allowed.
• Patients must have clinical features of high-risk disease, at time of initial diagnosis or initial assessment prior to enrollment, which may include one or more of the following:
• High-risk cytogenetic abnormalities, including t(4;14), t(14;16), t(14;20), del17p13, del1p, or gain 1q with del1p by FISH, with a cutoff point of 20% or greater.
• Beta-2-microglobulin \>5.5 mg/L with normal kidney function test per the institutional reference.
• Presence of extramedullary disease defined as soft tissue plasmacytoma (excluding Paramedullary/Paraskeletal plasmacytoma)
• ≥ 3 focal lesions on F18-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging
• LDH ≥ 360 U/L (Rule out hemolysis and infection; contact Principal Investigator if any doubt.)
• Circulating plasma cells ≥5 percent of white blood cells on conventional peripheral blood smear (manual white blood cell differential count) or peripheral blood flow cytometry.
• ECOG ≤ 2, unless solely due to symptoms of MM-related bone disease.
• Patients must have a platelet count ≥ 50,000/μL and hemoglobin level of ≥7.5 g/dl and absolute neutrophilic count (ANC) of 1.0x10\^9/L unless lower levels are explained by extensive BM plasmacytosis.
• Patients must be at least 18 years of age and not older than 75 years of age at the time of consent.
• Patients must have adequate renal function with baseline serum creatinine level \< 3 mg/dL and estimated creatinine clearance ≥30 mL/min. Creatinine clearance may be calculated using Cockcroft-Gault, eGFR (MDRD), or CKD-epi formula and baseline Alanine Aminotransferase (ALT) \< 3x Upper Limit of Normal (ULN).
• Patients must have an ejection fraction by echocardiogram (ECHO) or Multigated Acquisition (MUGA) scan ≥ 45%
• Patients must have adequate pulmonary function studies \> 50% of predicted on mechanical aspects (FEV1, FVC, etc.) and diffusion capacity (DLCO) \> 50% of predicted. If the patient is unable to complete pulmonary function tests (PFT) due to MM related pain or other conditions, an exception may be granted if the Principal Investigator documents that the patient is a candidate for high dose therapy.

You may not qualify if:

• Poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
• Patients must not have prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, low Gleason score prostate cancer on active surveillance or having had surgery/radiation with curative intent within one year of consent or other cancer for which the patient has not received treatment for one year prior to consent. Other cancers will only be acceptable if the patient's life expectancy exceeds five years.
• Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of any component of the treatment regimen. Or subject is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of any component of the treatment regimen. Women of childbearing potential (WOCBP) must have a negative pregnancy documented within one week of consent. Subjects of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and patients must be excluded if FEV1 is \<50% of predicted normal.
• Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note that patients who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study.
• Active autoimmune disease
• Active systematic viral, fungal or bacterial infection, requiring systemic therapy.
• Clinically significant cardiac disease, including Myocardial infarction within 6 months before consent, or Uncontrolled cardiac arrhythmia or unstable or uncontrolled disease/condition related to or affection cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class 3-4) (Appendix 1)
• Patient is:
• seropositive for human immunodeficiency virus (HIV)
• seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]. Subjects with resolved infection (i.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\] must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those with active infection will be excluded. Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) and a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
• Seropositive for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy).
• Patients who received plasmapheresis within 28 days of start of study treatment at Induction with Dara-KRD.
• Patients with focal radiation therapy within 14 days prior to consent with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma.
• Known history of allergy to Captisol ® (a cyclodextrin derivative used to solubilize carfilzomib).

Sponsors & Collaborators

• University of Arkansas: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72120, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Maintenance; Melphalan

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)

Health Care Facilities Workforce and Services; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Central Study Contacts

Joseph A Holley

CONTACT

501-686-8274; jaholley@uams.edu

Study Design

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

Study Record Dates

• First Submitted: May 23, 2025
• First Posted: June 19, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2032
• Last Updated: March 3, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)