Phase 1/2 Study of REGN5458 in Adult Patients With Relapsed or Refractory Multiple Myeloma
- Registration Number
- NCT03761108
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
The main purpose of this study is to learn about the safety of REGN5458 and to find out what is the best dose of REGN5458 to give to patients with multiple myeloma. An additional purpose is to look for any signs that REGN5458 can treat cancer.
The study is looking at several other research questions, including:
* Side effects that may be experienced by people receiving REGN5458
* How REGN5458 works in the body
* How much REGN5458 is present in the blood
* How REGN5458 may work to treat cancer
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 387
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Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
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Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria
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Patients must have myeloma that is response-evaluable according to the 2016 IMWG response criteria as defined in the protocol.
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Phase 1, Part 1 (Dose Escalation): Patients with MM who have exhausted all therapeutic options that are expected to provide meaningful clinical benefit, either through disease relapse, treatment refractory disease or intolerance of the therapy and including either:
a. Progression on or after at least 3 lines of therapy, or intolerance of therapy, including a proteasome inhibitor, an Immunomodulatory agent (IMiD), and an anti-CD38 antibody, OR b. Progression on or after an anti-CD38 antibody and have disease that is "double refractory" to a proteasome inhibitor and an IMiD, or intolerance of therapy. The anti-CD38 antibody may have been administered alone or in combination with another agent such as a proteasome inhibitor (PI). Refractory disease is defined as lack of response or relapse within 60 days of last treatment.
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Phase 1, Part 2 (SC Administration): Patients with MM whose disease meets the following criteria:
a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple-refractory, defined as being refractory to prior treatment with at least 1 anti-CD38 antibody, a proteasome inhibitor, and an IMiD.
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Phase 2 (Cohorts 1 and 2):
Patients with MM whose disease meets the following criteria:
a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody.
- Phase 2 (Cohort 3):
Patients with MM whose disease meets the following criteria:
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Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR
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Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody.
- Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or <25% response to therapy.
AND, for ALL patients, if they have relapsed after a BCMA-directed CAR-T cellular therapy then:
• Treatment with a CAR-T must have been associated with a response of PR or better, and
• If CAR-T cellular therapy was the most recent prior therapy, excluding corticosteroids, then treatment must have been a minimum of 60 days prior to treatment with REGN5458.
Key
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Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis, (excluding myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 2. Patients with known MM brain lesions or meningeal involvement 3. Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan (MUGA) 4. Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific antibodies and BiTEs. Note: BCMA antibody-drug conjugates are not excludedand BCMA-directed CAR-T treatment is not excluded in Phase 2 Cohort 3.
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History of allogeneic stem cell transplantation at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment
Note 1: Other protocol defined inclusion / exclusion criteria apply Note 2: US enrollment completed
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Linvoseltamab - Phase 2 - Cohort 1 Linvoseltamab Low Dose of REGN5458/linvoseltamab IV monotherapy. Linvoseltamab - Phase 2 - Cohort 2 Linvoseltamab High Dose of REGN5458/linvoseltamab IV monotherapy. Linvoseltamab - Phase 1 Linvoseltamab Phase 1 has two parts. Part 1, consists of REGN5458/linvoseltamab intravenous (IV) dose escalation and Part 2, consists of subcutaneous (SC) administration. Note: subcutaneous (SC) administration is not applicable for US. Linvoseltamab - Phase 2 - Cohort 3 Linvoseltamab Anti-interleukin (IL)-6 receptor (R) prophylactic therapy followed by high dose of IV dose of REGN5458 monotherapy. Note: Cohort 3 is not applicable for US.
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) as determined by an Independent Review Committee (IRC) Up to 5 years Phase 2, cohorts 1 and 2
ORR of IV REGN5458 as assessed by investigator in patients who have progressed Up to 5 years Phase 2, cohort 3 Note: Phase 2, Cohort 3 is not applicable for US.
Incidence and severity of adverse events of special interest (AESI) Up to 5 years Phase 1 Note: Phase 1, part 2 is not applicable for US.
Concentrations of REGN5458 in serum over time Up to 5 years Phase 1, part 2 and Phase 2, for Japanese cohort only
Incidence and severity of cytokine release syndrome (CRS) with REGN5458 Up to 5 years Phase 2, cohort 3 Note: Phase 2, Cohort 3 is not applicable for US.
Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period Up to 28 days Phase 1 and Phase 2 for Japanese cohort only
Incidence and severity of treatment-emergent adverse events (TEAEs) Up to 5 years Phase 1 Note: Phase 1, part 2 is not applicable for US.
- Secondary Outcome Measures
Name Time Method Duration of response (DOR) as determined by an IRC, measured using the IMWG criteria Up to 5 years Phase 2, cohorts 1 and 2
Incidence and severity of TEAEs with REGN5458 Up to 5 years Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
Titer of anti-drug antibodies (ADAs) to REGN5458 over time Up to 5 years Phase 1 and Phase 2 Note: Phase 1, part 2 and Phase 2, Cohort 3 is not applicable for US.
PFS as determined by an investigator, measured using the IMWG criteria Up to 5 years Phase 1 and Phase 2, cohorts 1 and 2 Note: Phase 1, part 2 is not applicable for US.
Incidence over time of anti-drug antibodies (ADAs) to REGN5458 Up to 5 years Phase 1 and Phase 2 Note: Phase 1, part 2 and Phase 2, Cohort 3 is not applicable for US.
Rate of MRD negative status status Up to 5 years Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
Effects of REGN5458 on patient-reported functions and symptoms per EORTC QLQ-C30 Up to 5 years Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
Concentrations of REGN5458 in the serum over time Up to 5 years Phase 1 part 1 and Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
ORR as determined by the investigator, measured using the IMWG criteria Up to 5 years Phase 1 and Phase 2, cohorts 1 and 2 Note: Phase 1, part 2 is not applicable for US.
Incidence of neutralizing antibodies (Nab) to REGN5458 over time Up to 5 years Phase 1 and Phase 2 Note: Phase 1, part 2 and Phase 2, Cohort 3 is not applicable for US.
Overall survival (OS) Up to 5 years Phase 1 and Phase 2 Note: Phase 1, part 2 and Phase 2, Cohort 3 is not applicable for US.
Effects of REGN5458 on patient-reported functions and symptoms per QLQ-MY20 Up to 5 years Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
DOR as determined by an investigator, measured using the International Myeloma Working Group (IMWG) criteria Up to 5 years Phase 1 and Phase 2, cohorts 1 and 2 Note: Phase 1, part 2 is not applicable for US.
Progression-free survival (PFS) as determined by an IRC, measured using the IMWG criteria Up to 5 years Phase 2, cohorts 1 and 2
Rate of minimal residual disease (MRD) negative status using the IMWG criteria Up to 5 years Phase 1 Note: Phase 1, part 2 is not applicable for US.
ORR as measured as determined by blinded IRC, as measured using the IMWG criteria Up to 5 years Phase 1, part 1 dose level 7 (DL7)
Effects of REGN5458 on health-related quality of life (HRQoL) and patient-reported symptoms and functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Up to 5 years 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."
Note: Phase 2, Cohort 3 is not applicable for US.Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per Quality of Life Questionnaire-Multiple Myeloma module 20 [QLQ-MY20]) Up to 5 years 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.
Note: Phase 2, Cohort 3 is not applicable for US.Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30 Up to 5 years Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
Effects of REGN5458 on general health status per EQ-5D-3L Up to 5 years Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
Incidence and severity of AESIs with REGN5458 Up to 5 years Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per EuroQoL-5 Dimension-3 Level Scale [EQ-5D-3L]) Up to 5 years Phase 2
The EQ-5D-3L is a self-administered generic standardized health status measure, consisting of an EQ-5D descriptive system and an EQ visual analog scale. The EQ-5D-3L descriptive system assesses 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 3-level scale: no problems, some problems, and extreme problems. The EQ visual analog scale component is a vertical visual analog scale used by patients to rate their health.
Note: Phase 2, Cohort 3 is not applicable for US.Change in patient-reported global health status/QoL per EORTC QLQ-C30 Baseline up to Up to 5 years Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
Trial Locations
- Locations (41)
Indiana University_Michigan Street
🇺🇸Indianapolis, Indiana, United States
Keio University Hospital
🇯🇵Tokyo, Japan
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Moffitt Cancer Center - McKinley Drive
🇺🇸Tampa, Florida, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
C. S. Mott_University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Barbara Ann Karmanos Cancer Center
🇺🇸Detroit, Michigan, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Ohio State University James Cancer Hospital
🇺🇸Columbus, Ohio, United States
Oregon Health and Science University (OHSU) Marquam Hill Campus
🇺🇸Portland, Oregon, United States
University of Texas MD Anderson Clinic
🇺🇸Houston, Texas, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
ZNA Psychiatrisch Ziekenhuis Stuivenberg
🇧🇪Antwerp, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
Universitatsklinikum Essen
🇩🇪Essen, North Rhine-Westphalia, Germany
Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR
🇩🇪Mainz, Rheinland-Pfalz, Germany
Universitatsklinikum Wurzburg
🇩🇪Würzburg, Germany
Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
🇯🇵Nagoya, Aichi, Japan
Nagoya City University Hospital
🇯🇵Nagoya, Aichi, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Chiba-ken, Japan
Gunma University Hospital
🇯🇵Maebashi, Gunma, Japan
Ibaraki Prefectural Central Hospital
🇯🇵Kasama-shi, Ibaraki, Japan
University Hospital Kyoto Prefectural Univ of Medicine
🇯🇵Kyoto City, Kyoto, Japan
Saitama Medical University International Medical Center
🇯🇵Hidaka, Saitama, Japan
Tokushima Prefectural Central Hospital
🇯🇵Tokushima-shi, Tokushima, Japan
Japanese Red Cross Medical Center. 4-1-22 Hiroo
🇯🇵Shibuya-ku, Tokyo, Japan
Japanese Red Cross Medical Center
🇯🇵Shibuya-ku, Tokyo, Japan
Center for Hematologic Malignancy
🇰🇷Goyang, Gyeonggi-do, Korea, Republic of
Seoul National University Cancer Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Yonsei University College of Medicine, Severance Hospital
🇰🇷Seoul, Korea, Republic of
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Catalonia, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Universitary Hospital La Princesa
🇪🇸Madrid, Salamanca, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Salamanca
🇪🇸Salamanca, Spain
Royal Marsden Hospital
🇬🇧Sutton, Surrey, United Kingdom