A Study to Assess the Safety and Anti-Tumor Activity of REGN7945 in Combination With Linvoseltamab in Adult Participants With Relapsed/Refractory Multiple Myeloma

Phase 2RecruitingNCT06669247

Regeneron Pharmaceuticals186 enrolled

Overview

This study is researching an experimental drug called REGN7945 in combination with another experimental drug called linvoseltamab, (also known as REGN5458) (each individually called a "study drug" or "study drugs" when combined). This study is the first time REGN7945 will be tested in humans. Linvoseltamab has previously been studied by itself (without other cancer drugs) in participants who had advanced multiple myeloma that returned and needed to be treated again after several other therapies had failed. The aim of the study is to see how safe, tolerable, and effective REGN7945 is when given in combination with linvoseltamab, compared with linvoseltamab alone. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug(s) * How many people treated with REGN7945 and linvoseltamab compared to linvoseltamab alone have improvement of their multiple myeloma and by how much * How long people benefit from receiving REGN7945 in combination with linvoseltamab compared with linvoseltamab alone * How much study drug(s) is in the blood at different times * Whether the body makes antibodies against the study drugs(s) (which could make the study drug(s) less effective or could lead to side effects) * If there is any change in pain and cancer-related symptoms, how well people are able to function, and their quality of life when taking the study drug(s)

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

186

Conditions

Relapsed/Refractory Multiple Myeloma

Interventions

LinvoseltamabDRUG

Administered per protocol

REGN7945+LinvoseltamabDRUG

Administered per protocol

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 as described in the protocol 2. Received at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 immunomodulatory imide drug (IMiD), and 1 proteasome inhibitor (PI) and have demonstrated disease progression on or after the last therapy, as defined in the protocol. Prior treatment with other BCMA directed immunotherapies, including BCMA CAR-T cells and BCMA antibody-drug conjugates (Phase 1 and 2), and with BCMA x CD3 bispecific antibodies (Phase 1 only), is allowed 3. Participants must have the measurable disease for response assessment as described in the protocol 4. Adequate hematologic, hepatic, and renal function as described in the protocol Key Exclusion Criteria: 1. Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis (including myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 2. Treatment with any systemic anti-cancer therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter 3. History of allogeneic stem cell transplantation within 6 months, or autologous stem cell transplantation within 12 weeks of the start of study treatment 4. Treatment with systemic corticosteroid treatment with more than 10 mg per day of prednisone or steroid equivalent within 72 hours of start of study drug 5. Participants who have known central nervous system (CNS) involvement with MM or known or suspected progressive multifocal leukoencephalopathy (PML), history of a neurocognitive condition or CNS disorder, or history of seizure within 12 months prior to study enrollment 6. Live or live attenuated vaccination within 28 days before first study drug administration with a vector that has replicative potential 7. Has received a COVID-19 vaccination within 1 week of planned start of study medication as described in the protocol 8. Myelodysplastic syndrome or another malignancy in the past 3 years, except for nonmelanoma skin cancer, in situ carcinoma, thyroid cancer, or low-risk early stage prostate adenocarcinoma, as described in the protocol 9. Significant cardiovascular disease as described in the protocol 10. Uncontrolled infection with HIV, Hep B or Hep C infection, or other uncontrolled infection, such as CMV, as described in the protocol 11. Known hypersensitivity to both allopurinol and rasburicase Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Locations (9)

Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

RECRUITING

Illawarra Cancer Care Centre

Wollongong, New South Wales, Australia

RECRUITING

Pindara Private Hospital

Benowa, Queensland, Australia

RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, Australia

RECRUITING

Alfred Hospital

Melbourne, Victoria, Australia

RECRUITING

St Vincents Hospital Melbourne

Melbourne, Victoria, Australia

RECRUITING

University College London Hospitals

London, United Kingdom

RECRUITING

St Thomas Hospital

London, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

Outcomes

Primary Outcomes

Incidence of dose limiting toxicities (DLTs) from the first dose of REGN7945 in combination with linvoseltamab

Phase 1

Time frame: Up to 21 days

Incidence of treatment emergent adverse events (TEAEs) during the treatment period with REGN7945 in combination with linvoseltamab

Phase 1

Time frame: Up to 5 years

Severity of TEAEs during the treatment period with REGN7945 in combination with linvoseltamab

Phase 1

Time frame: 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 therapy

Phase 2

Time frame: 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

Time frame: 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 therapy

Phase 2

Time frame: 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

Time frame: Within 12 weeks of starting cycle 1

Secondary Outcomes

Incidence of TEAEs

Phase 1 and Phase 2

Time frame: Up to 5 years

Severity of TEAEs

Phase 1 and Phase 2

Time frame: Up to 5 years

Concentrations of REGN7945 in the serum

Phase 1 and Phase 2

Time frame: Up to 5 years

Concentrations of linvoseltamab in the serum

Phase 1 and Phase 2

Time frame: Up to 5 years

Incidence of anti-drug antibodies (ADA) to REGN7945

Phase 1 and Phase 2

Time frame: Up to 5 years

Titer of ADA to REGN7945

Phase 1 and Phase 2

Time frame: Up to 5 years

Incidence of ADA to linvoseltamab

Phase 1 and Phase 2

Time frame: Up to 5 years

Titer of ADA to linvoseltamab

Phase 1 and Phase 2

Time frame: Up to 5 years

Change 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 1 and Phase 2 The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported quality of life using one global health status/quality of life (GHS/QoL) scale, 5 functioning scales (physical, role, emotional, cognitive, and social) ranging from from 1 = "very poor" to 5 = "excellent" and 9 symptom scales/items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) among patients with cancer, ranging from 1 = "not at all" to 9 = "very much" higher scores indicate higher symptom burden.

Time frame: Up to 5 years

Change in EORTC QLQ-C30 Physical Functioning (PF)

Phase 1 and Phase 2

Time frame: Up to 5 years

Change in EORTC QLQ-C30 Role Functioning (RF)

Phase 1 and Phase 2

Time frame: Up to 5 years

Change in EORTC QLQ-C30 pain

Phase 1 and Phase 2

Time frame: Up to 5 years

Change in EORTC QLQ-C30 fatigue

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to definitive deterioration in EORTC QLQ-C30 GHS/QoL

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to definitive deterioration in EORTC QLQ-C30 PF

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to definitive deterioration in EORTC QLQ-C30 RF

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to definitive deterioration in EORTC QLQ-C30 pain

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to definitive deterioration in EORTC QLQ-C30 fatigue

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to first improvement in EORTC QLQ-C30 GHS/QoL

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to first improvement in EORTC QLQ-C30 PF

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to first improvement in EORTC QLQ-C30 RF

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to first improvement in EORTC QLQ-C30 pain

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to first improvement in EORTC QLQ-C30 fatigue

Phase 1 and Phase 2

Time frame: Up to 5 years

Change in EORTC QLQ-Multiple Myeloma Module (MY20) Disease Symptoms (DS)

Phase 1 and Phase 2 The EORTC QLQ-MY20 is a self -administered instrument to assess QoL in persons with Multiple Myeloma (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.

Time frame: Up to 5 years

Change in EORTC QLQ-MY20 Treatment Side Effects (TSE)

Phase 1 and Phase 2

Time frame: Up to 5 years

Change in EORTC QLQ-MY20 Body Image (BI)

Phase 1 and Phase 2

Time frame: UP to 5 years

Change in EORTC QLQ-MY20 Future Perspective (FP)

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to definitive deterioration in EORTC QLQ-MY20 DS

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to definitive deterioration in EORTC QLQ-MY20 TSE

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to definitive deterioration in EORTC QLQ-MY20 BI

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to definitive deterioration in EORTC QLQ-MY20 FP

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to first improvement in EORTC QLQ-MY20 DS

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to first improvement in EORTC QLQ-MY20 TSE

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to first improvement in EORTC QLQ-MY20 BI

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to first improvement in EORTC QLQ-MY20 FP

Phase 1 and Phase 2

Time frame: Up to 5 years

Change in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS) (EQ-5D-5L VAS)

Phase 1 and Phase 2 The EQ-5D-5L is a generic questionnaire that measures Health-Related Quality of Life (HRQoL) across 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) across 5 levels (no problems, slight problems, some problems, severe problems and extreme problems) and a visual analogue scale (VAS).

Time frame: Up to 5 years

Time to definitive deterioration in EQ-5D-5L VAS

Phase 1 and Phase 2

Time frame: Up to 5 years

Time to first improvement in EQ-5D-5L VAS

Phase 1 and Phase 2

Time frame: Up to 5 days

Patient-reported overall impact of treatment toxicity measured by Functional Assessment of Cancer Therapy (FACIT)-Item GP5

Phase 1 and Phase 2 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).

Time frame: Up to 5 years

Objective Response Rate (ORR) as measured by IMWG criteria as determined by the investigator

Phase 1

Time frame: Up to 5 years

Complete response (CR) rate as measured by IMWG criteria as determined by the investigator

Phase 1

Time frame: Up to 5 years

Duration of response (DOR) by IMWG criteria as determined by the investigator

Phase 1

Time frame: Up to 5 years

Progression Free Survival (PFS) as measured by IMWG criteria as determined by the investigator

Phase 1

Time frame: Up to 5 years

Achievement of Minimal Residual Disease (MRD) negative status (at 10^5) in participants in CR or better

Phase 1

Time frame: Up to 5 years

Overall survival (OS)

Phase 1

Time frame: Up to 5 years

Central Contacts

Clinical Trials Administrator

CONTACT

844-734-6643 clinicaltrials@regeneron.com

Data from ClinicalTrials.gov

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