Relapsed/Refractory Multiple Myeloma
Conditions
Keywords
R/RMM
Brief summary
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)
Interventions
DRUGLinvoseltamab
Administered per protocol
DRUGREGN7945+Linvoseltamab
Administered per protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1: non-randomized dose escalation Phase 2: randomized dose expansion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose limiting toxicities (DLTs) from the first dose of REGN7945 in combination with linvoseltamab | Up to 21 days | Phase 1 |
| Incidence of treatment emergent adverse events (TEAEs) during the treatment period with REGN7945 in combination with linvoseltamab | Up to 5 years | Phase 1 |
| Severity of TEAEs during the treatment period with REGN7945 in combination with linvoseltamab | Up to 5 years | Phase 1 |
| 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 | Within 12 weeks of starting cycle 1 | Phase 2 |
| VGPR or better as determined by the investigator using the IMWG response criteria in patients receiving linvoseltamab monotherapy | Within 12 weeks of starting cycle 1 | Phase 2 |
| Partial Response (PR) or better as determined by the investigator using the IMWG response criteria in patients receiving combination therapy | Within 12 weeks of starting cycle 1 | Phase 2 |
| PR or better as determined by the investigator using the IMWG response criteria in patients receiving linvoseltamab monotherapy | Within 12 weeks of starting cycle 1 | Phase 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of TEAEs | Up to 5 years | Phase 1 and Phase 2 |
| Severity of TEAEs | Up to 5 years | Phase 1 and Phase 2 |
| Concentrations of REGN7945 in the serum | Up to 5 years | Phase 1 and Phase 2 |
| Concentrations of linvoseltamab in the serum | Up to 5 years | Phase 1 and Phase 2 |
| Incidence of anti-drug antibodies (ADA) to REGN7945 | Up to 5 years | Phase 1 and Phase 2 |
| Titer of ADA to REGN7945 | Up to 5 years | Phase 1 and Phase 2 |
| Incidence of ADA to linvoseltamab | Up to 5 years | Phase 1 and Phase 2 |
| Titer of ADA to linvoseltamab | Up to 5 years | Phase 1 and Phase 2 |
| 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) | Up to 5 years | 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. |
| Change in EORTC QLQ-C30 Physical Functioning (PF) | Up to 5 years | Phase 1 and Phase 2 |
| Change in EORTC QLQ-C30 Role Functioning (RF) | Up to 5 years | Phase 1 and Phase 2 |
| Change in EORTC QLQ-C30 pain | Up to 5 years | Phase 1 and Phase 2 |
| Change in EORTC QLQ-C30 fatigue | Up to 5 years | Phase 1 and Phase 2 |
| Time to definitive deterioration in EORTC QLQ-C30 GHS/QoL | Up to 5 years | Phase 1 and Phase 2 |
| Time to definitive deterioration in EORTC QLQ-C30 PF | Up to 5 years | Phase 1 and Phase 2 |
| Time to definitive deterioration in EORTC QLQ-C30 RF | Up to 5 years | Phase 1 and Phase 2 |
| Time to definitive deterioration in EORTC QLQ-C30 pain | Up to 5 years | Phase 1 and Phase 2 |
| Time to definitive deterioration in EORTC QLQ-C30 fatigue | Up to 5 years | Phase 1 and Phase 2 |
| Time to first improvement in EORTC QLQ-C30 GHS/QoL | Up to 5 years | Phase 1 and Phase 2 |
| Time to first improvement in EORTC QLQ-C30 PF | Up to 5 years | Phase 1 and Phase 2 |
| Time to first improvement in EORTC QLQ-C30 RF | Up to 5 years | Phase 1 and Phase 2 |
| Time to first improvement in EORTC QLQ-C30 pain | Up to 5 years | Phase 1 and Phase 2 |
| Time to first improvement in EORTC QLQ-C30 fatigue | Up to 5 years | Phase 1 and Phase 2 |
| Change in EORTC QLQ-Multiple Myeloma Module (MY20) Disease Symptoms (DS) | Up to 5 years | 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. |
| Change in EORTC QLQ-MY20 Treatment Side Effects (TSE) | Up to 5 years | Phase 1 and Phase 2 |
| Change in EORTC QLQ-MY20 Body Image (BI) | UP to 5 years | Phase 1 and Phase 2 |
| Change in EORTC QLQ-MY20 Future Perspective (FP) | Up to 5 years | Phase 1 and Phase 2 |
| Time to definitive deterioration in EORTC QLQ-MY20 DS | Up to 5 years | Phase 1 and Phase 2 |
| Time to definitive deterioration in EORTC QLQ-MY20 TSE | Up to 5 years | Phase 1 and Phase 2 |
| Time to definitive deterioration in EORTC QLQ-MY20 BI | Up to 5 years | Phase 1 and Phase 2 |
| Time to definitive deterioration in EORTC QLQ-MY20 FP | Up to 5 years | Phase 1 and Phase 2 |
| Time to first improvement in EORTC QLQ-MY20 DS | Up to 5 years | Phase 1 and Phase 2 |
| Time to first improvement in EORTC QLQ-MY20 TSE | Up to 5 years | Phase 1 and Phase 2 |
| Time to first improvement in EORTC QLQ-MY20 BI | Up to 5 years | Phase 1 and Phase 2 |
| Time to first improvement in EORTC QLQ-MY20 FP | Up to 5 years | Phase 1 and Phase 2 |
| Change in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS) (EQ-5D-5L VAS) | Up to 5 years | 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 to definitive deterioration in EQ-5D-5L VAS | Up to 5 years | Phase 1 and Phase 2 |
| Time to first improvement in EQ-5D-5L VAS | Up to 5 days | Phase 1 and Phase 2 |
| Patient-reported overall impact of treatment toxicity measured by Functional Assessment of Cancer Therapy (FACIT)-Item GP5 | Up to 5 years | 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). |
| Objective Response Rate (ORR) as measured by IMWG criteria as determined by the investigator | Up to 5 years | Phase 1 |
| Complete response (CR) rate as measured by IMWG criteria as determined by the investigator | Up to 5 years | Phase 1 |
| Duration of response (DOR) by IMWG criteria as determined by the investigator | Up to 5 years | Phase 1 |
| Progression Free Survival (PFS) as measured by IMWG criteria as determined by the investigator | Up to 5 years | Phase 1 |
| Achievement of Minimal Residual Disease (MRD) negative status (at 10^5) in participants in CR or better | Up to 5 years | Phase 1 |
| Overall survival (OS) | Up to 5 years | Phase 1 |
Countries
Australia, United Kingdom
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed