A Trial to Study if REGN17372 in Combination With Linvoseltamab is Tolerable for Adult Participants With Relapsed/Refractory Multiple Myeloma

A FIH Phase 1/2 Study to Assess Safety, Tolerability, and Preliminary Anti-Tumor Activity of REGN17372, an Anti-GPRC5D x Anti-CD28 Costimulatory Bispecific Monoclonal Antibody, in Combination With Linvoseltamab, an Anti-BCMA x Anti-CD3 Bispecific Monoclonal Antibody, in Participants With Relapsed/Refractory Multiple Myeloma

This study is researching a drug called REGN17372 used with another drug called linvoseltamab (each individually called "study drug" or "study drugs" when combined) in participants with relapsed (when a tumor comes back) or refractory (when a tumor does not respond to treatment) multiple myeloma. This study is the first time REGN17372 will be given to humans.

The aim of the study is to understand if REGN17372 can be given safely with linvoseltamab, and if so, what dosing regimen should be used for this treatment combination, in comparison with linvoseltamab alone.

The study is looking at:

• What side effects may happen from taking REGN17372 with linvoseltamab
• How well REGN17372 and linvoseltamab, or linvoseltamab alone, work in treating multiple myeloma
• What is the best dose of REGN17372 when given with linvoseltamab
• How much study drug(s) are in the blood at different times
• Whether the body makes antibodies against the study drugs (which could make the study drugs less effective or could lead to side effects)
• If and how REGN17372 and linvoseltamab affect the overall quality of life, daily activities, symptoms and treatment side effects based on participant own feedback (Phase 2)

Study Overview

• Status: Recruiting
• Conditions: Relapsed Refractory Multiple Myeloma (RRMM)
• Intervention / Treatment: Drug: Linvoseltamab; Drug: REGN17372+Linvoseltamab

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Recruiting
      • Prince of Wales Hospital
    • Wollongong, New South Wales, Australia, 2500
      • Recruiting
      • Illawarra Cancer care centre, Wollongong Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Recruiting
      • St Vincents Hospital Melbourne
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter Maccallum Cancer Centre
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Alfred Hospital
• Greece
  • Attica
    • Athens, Attica, Greece, 10676
      • Recruiting
      • Evangelismos General Hospital
    • Athens, Attica, Greece, 11528
      • Recruiting
      • Alexandra Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Participants with RRMM who have exhausted (or are not a candidate for) all therapeutic options that are expected to provide meaningful clinical benefit and have received at least 3 lines of therapy as defined in the protocol
2. ECOG performance status score ≤1
3. Participants must have measurable disease for response assessment as described in the protocol
4. Adequate hematologic, cardiac, hepatic, and renal function, as described in the protocol

Key Exclusion Criteria:

1. Participants with non-secretory MM, active plasma cell leukemia, known amyloidosis, Waldenström macroglobulinemia, or known POEMS syndrome as defined in the protocol
2. Participants who have known MM brain lesions or CNS involvement
3. Participants with a history of PML, a neurocognitive condition or CNS movement disorder, or a history of seizure within 12 months prior to entering screening
4. Prior treatment with GPRC5D-directed immunotherapies (phase 1 and phase 2) and/or prior treatment with a BCMAxCD3 bispecific antibody (phase 2)

Note: Other protocol defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REGN17372 + Linvoseltamab; Phase 1 Phase 2	Drug: REGN17372+Linvoseltamab; Administered per the protocol
Active Comparator: Linvoseltamab monotherapy; Phase 2	Drug: Linvoseltamab; Administered per protocol; Other Names: REGN5458; Lynozyfic™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Dose Limiting Toxicities (DLTs) from the first dose of REGN17372 in combination with linvoseltamab	Phase 1	Up to 35 days
Occurrence of Treatment Emergent Adverse Events (TEAEs) associated with REGN17372 in combination with linvoseltamab	Phase 1	Up to 5 years
Severity of TEAEs associated with REGN17372 in combination with linvoseltamab	Phase 1	Up to 5 years
Very Good Partial Response (VGPR) or better as determined by the investigator using the International Myeloma Working Group (IMWG) response criteria in patients receiving combination study drugs	Phase 2	Within 12 weeks of starting cycle 1
VGPR or better as determined by the investigator using the IMWG response criteria in patients receiving Linvoseltamab monotherapy	Phase 2	Within 12 weeks of starting cycle 1
Partial Response (PR) or better as determined by the investigator using the IMWG response criteria in patients receiving combination study drugs	Phase 2	Within 12 weeks of starting cycle 1
PR or better as determined by the investigator using the IMWG response criteria in patients receiving Linvoseltamab monotherapy	Phase 2	Within 12 weeks of starting cycle 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of ADA to linvoseltamab	Phase 1 and Phase 2	Up to 5 years
Concentrations of REGN17372 in serum	Phase 1 and Phase 2	Up to 5 years
Concentrations of linvoseltamab in serum	Phase 1 and Phase 2	Up to 5 years
Occurrence of Anti-Drug Antibodies (ADA) to REGN17372	Phase 1 and Phase 2	Up to 5 years
Magnitude of ADA to REGN17372	Phase 1 and Phase 2	Up to 5 years
Magnitude of ADA to linvoseltamab	Phase 1 and Phase 2	Up to 5 years
Objective Response Rate (ORR) as assessed by IMWG response criteria as determined by the investigator	Phase 1 and Phase 2	Up to 5 years
Complete response (CR) as assessed by IMWG response criteria as determined by the investigator	Phase 1 and Phase 2	Up to 5 years
VGPR as assessed by IMWG response criteria, as determined by the investigator	Phase 1 and Phase 2	Up to 5 years
Duration of Response (DOR) as assessed by IMWG criteria as determined by the investigator	Phase 1 and Phase 2	Up to 5 years
Progression Free Survival (PFS) as assessed by IMWG criteria as determined by the investigator	Phase 1 and Phase 2	Up to 5 years
Minimal Residual Disease (MRD) negative status (at 10^-5) in participants in CR or better	Phase 1 and Phase 2	Up to 5 years
Overall Survival (OS)	Phase 1 and Phase 2	Up to 5 years
ORR as assessed using the IMWG response criteria as determined by the investigator in patients receiving combination study drugs	Phase 1	Within 12 weeks of starting cycle 1
VGPR assessed using IMWG criteria as determined by the investigator in patients receiving combination study drugs	Phase 1	Within 12 weeks of starting cycle 1
Incidence of TEAEs	Phase 2	Up to 5 years
Severity of TEAEs	Phase 2	Up to 5 years
Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) Global Health Status / Quality of Life (GHS/QoL)	Phase 2 The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much"	Up to 5 years
Change from baseline in EORTC QLQ-C30 Physical Functioning (PF)	Phase 2	Up to 5 years
Change from baseline in EORTC QLQ-C30 Role Functioning (RF)	Phase 2	Up to 5 years
Change from baseline in EORTC QLQ-C30 pain	Phase 2	Up to 5 years
Change from baseline in EORTC QLQ-C30 fatigue	Phase 2	Up to 5 years
Time to definitive deterioration in EORTC QLQ-C30 GHS/QoL	Phase 2	Up to 5 years
Time to definitive deterioration in EORTC QLQ-C30 PF	Phase 2	Up to 5 years
Time to definitive deterioration in EORTC QLQ-C30 RF	Phase 2	Up to 5 years
Time to definitive deterioration in EORTC QLQ-C30 pain	Phase 2	Up to 5 years
Time to definitive deterioration in EORTC QLQ-C30 fatigue	Phase 2	Up to 5 years
Time to first improvement in EORTC QLQ-C30 GHS/QoL	Phase2	Up to 5 years
Time to first improvement in EORTC QLQ-C30 PF	Phase 2	Up to 5 years
Time to first improvement in EORTC QLQ-C30 RF	Phase 2	Up to 5 years
Time to first improvement in EORTC QLQ-C30 pain	Phase 2	Up to 5 years
Time to first improvement in EORTC QLQ-C30 fatigue	Phase 2	Up to 5 years
Change from baseline in EORTC QLQ-Multiple Myeloma Module (MY20) Disease Symptoms (DS)	Phase 2 The EORTC QLQ-MY20 is a self -administered instrument to assess QoL in persons with MM. This 20-item questionnaire measures the following domains: symptom scales, including disease symptoms (6 items) and symptoms related to side effects of treatment (10 items); function scale and future perspective (3 items); and body image (1 item). A high score represents a high level of symptoms or problems	Up to 5 years
Time to definitive deterioration in EORTC QLQ-MY20 DS	Phase 2	Up to 5 years
Time to first improvement in EORTC QLQ-MY20 DS	Phase 2	Up to 5 years
Change from baseline in EORTC QLQ-MY20 Treatment Side Effects (TSE)	Phase 2	Up to 5 years
Time to definitive deterioration in EORTC QLQ-MY20 TSE	Phase 2	Up to 5 years
Time to first improvement in EORTC QLQ-MY20 TSE	Phase 2	Up to 5 years
Change from baseline in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS) (EQ-5D-5L VAS)	Phase 2 The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems	Up to 5 years
Time to definitive deterioration in EQ-5D-5L VAS	Phase 2	Up to 5 years
Time to first improvement in EQ-5D-5L VAS	Phase 2	Up to 5 years
Patient-reported overall impact of treatment toxicity measured by Functional Assessment of Cancer Therapy (FACIT) Item GP5	Phase 2 The FACIT Item GP5 will be used to assess the patient-reported impact of treatment toxicity that uses a single item "I am bothered by side effects of treatment" on a 5-point scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much)	Up to 5 years
Patient-reported tolerability as measured by the Patient Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE)	Phase 2 The PRO-CTAE questionnaire assesses side effects and symptoms in cancer clinical trials using a PRO-CTCAE score. The PRO-CTCAE includes an item library of 124 items representing 78 symptomatic AEs drawn from the CTCAE	Up to 5 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2026
• Primary Completion (Estimated): September 30, 2033
• Study Completion (Estimated): September 30, 2033

Study Registration Dates

• First Submitted: March 2, 2026
• First Submitted That Met QC Criteria: March 2, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): September 11, 2026
• Last Update Submitted That Met QC Criteria: September 9, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: B-cell maturation antigen (BCMA); Anti-CD3 monoclonal antibodies (mAbs); G-protein-coupled receptor class C group 5 member D (GPRC5D)
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma
• Other Study ID Numbers: R17372-HM-2493; 2025 (U.S. NIH Grant/Contract: Faculty of Social Sciences Scientific Grant at the University of Gdańsk); 2025-522776-93-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes