Horizon Two Adaptive Platform Study in High Risk Newly Diagnosed Multiple Myeloma

NCT07053436 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: MMRC-100
• Study Type: interventional
• Target: 300
• Locations: 0 countries
• Sites: N/A

Brief Summary

The Multiple Myeloma Research Consortium (MMRC) Horizon Two trial is a master protocol, multi-center, phase II randomized adaptive platform trial designed to efficiently evaluate multiple investigational therapies in high-risk newly diagnosed multiple myeloma patients using an integrated and patient-centric clinical research platform that enables longitudinal learning and sharing of knowledge and investigates multiple novel therapeutic strategies within one trial platform.

Conditions

High Risk Newly Diagnosed Multiple Myeloma

Keywords

Horizon; Horizon Two; MMRC; HR NDMM

Outcome Measures

Primary Outcomes (2)

• Sustained measurable residual disease (MRD) negativity

  Sustained MRD negativity is defined as MRD negativity at a minimum threshold of one myeloma cell in one hundred thousand nucleated bone marrow cells at MRD assessments

  2 years post randomization

• Progression Free Survival

  PFS is defined as time from randomization to disease progression or death from any cause. Participants who have not progressed or died are censored at the date last known progression-free.

  through study completion, roughly 5 years

Secondary Outcomes (7)

• Objective response rate (ORR)

  2 years

• Best overall response

  2 years

• Two-year progression free survival rate

  24 months after randomization

• Overall survival (OS)

  through study completion, average of 5 years

• Duration of response (DoR)

  2 years

Study Arms (2)

Control Arm: Isa-KRd with Autologous Stem Cell Transplant

ACTIVE COMPARATOR

Appendix A to the MMRC Horizon Two High Risk Newly Diagnosed Multiple Myeloma Master Protocol: Isa-KRd with Autologous Stem Cell Transplant in Patients with High Risk Newly Diagnosed Multiple Myeloma

Drug: Monoclonal Antibody with Stem Cell Transplant

Induction, Consolidation, and Maintenance Therapy Combining Linvoseltamab and Triplet Therapy

EXPERIMENTAL

Appendix B to the MMRC Horizon Two High Risk Newly Diagnosed Multiple Myeloma Master Protocol: Induction, Consolidation, and Maintenance Therapy Combining Linvoseltamab and Triplet Therapy in Patients with High Risk Newly Diagnosed Multiple Myeloma

Drug: Bispecific Monoclonal Antibody and Triplet Therapy

Interventions

Bispecific Monoclonal Antibody and Triplet Therapy DRUG

Induction, Consolidation, and Maintenance Therapy Combining Linvoseltamab and Triplet Therapy

Also known as: Linvoseltamab

Induction, Consolidation, and Maintenance Therapy Combining Linvoseltamab and Triplet Therapy

Monoclonal Antibody with Stem Cell Transplant DRUG

Isatuximab-KRd with Autologous Stem Cell Transplant

Also known as: Isatuximab

Control Arm: Isa-KRd with Autologous Stem Cell Transplant

Eligibility Criteria

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

You may qualify if:

• Voluntarily agree to participate by giving written informed consent
• ≥18 years of age
• Symptomatic and transplant eligible newly diagnosed multiple myeloma histologically confirmed per IMWG criteria that is high-risk as defined by at least one of the following:
• Del(17p) (CCF ≥ 20%, by analyses conducted on CD138-positive/purified cells) and/or TP53 mutation assessed by NGS
• One of these translocations-t(4;14) or t(14;16) or t(14;20)-co-occurring with +1q and/or del(1p32)
• Monoallelic del(1p32) along with +1q, or biallelic del(1p32)
• High β2M (≥5.5 mg/dL) with normal creatinine (\<1.2 mg/dL)
• Presence of extra-medullary disease non-contiguous with bone at diagnosis (by PET-CT or Whole Body MRI)
• Primary plasma cell leukemia (circulating plasma cells \> 5% at diagnosis)
• No more than 2 cycles of NCCN listed induction therapy for multiple myeloma
• Measurable disease, per IMWG criteria, at time of diagnosis defined as one of the following:
• Serum M-protein at diagnosis ≥ 0.5g/dL (0.3 g/dL or above if IgA subtype)
• Urine M-protein ≥ 200 mg/24hours
• Serum free light chain difference \> 100 mg/L
• Plasmacytoma ≥ 2cm

You may not qualify if:

• Major concurrent illness or organ dysfunction including but not limited to the following:
• POEMS syndrome
• Symptomatic major organ involvement AL amyloidosis
• History of allergy or known hypersensitivity to any of the trial therapies or any of their excipients, or contraindication to any of the trial therapies as outlined in the local prescribing information (e.g., United States Prescribing Information \[USPI\])
• Complete spinal cord compression or CNS involvement
• Known leptomeningeal disease
• Allogeneic tissue/solid organ transplant recipients with chronic GVHD requiring steroid equivalent dose of \> 20 mg prednisone
• Active infection requiring treatment
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
• Psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
• Legally incapacitated or has limited legal capacity
• Persons who are pregnant or breastfeeding

Sponsors & Collaborators

• Multiple Myeloma Research Consortium: lead

MeSH Terms

Interventions

Antibodies, Bispecific; Antibodies, Monoclonal; Stem Cell Transplantation; isatuximab

Intervention Hierarchy (Ancestors)

Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Hearn Jay Cho, MD, PhD

  Multiple Myeloma Research Foundation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jessica Vandermark

CONTACT

2036520457; vandermarkj@themmrf.org

Mercedes Martillo

CONTACT

2036520457; martillom@themmrf.org

Study Design

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

Model Details: Adaptive Platform

Study Record Dates

• First Submitted: May 28, 2025
• First Posted: July 8, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2035
• Study Completion (Estimated): October 12, 2035
• Last Updated: July 8, 2025

Record last verified: 2025-06