Description:
In the phase 1 portion of the study, the primary objectives are to assess the safety,
tolerability, and dose-limiting toxicities (DLTs) and to determine a recommended phase 2 dose
regimen (RP2DR) of REGN5459 as monotherapy in patients with relapsed or refractory multiple
myeloma (MM) who have exhausted all therapeutic options that are expected to provide
meaningful clinical benefit.
In the phase 2 portion of the study, the primary objective is to assess the preliminary
anti-tumor activity of REGN5459 as measured by objective response rate (ORR).
In the phase 1 and phase 2 portion, the secondary objectives of the study are:
- To assess the preliminary anti-tumor activity of REGN5459 as measured by duration of
response (DOR), progression-free survival (PFS), rate of minimal residual disease (MRD)
negative status, and overall survival (OS)
- To evaluate the pharmacokinetic (PK) properties of REGN5459
- To characterize the immunogenicity of REGN5459
- To evaluate the effects of REGN5459 on patient-reported quality of life (QoL), symptoms,
functioning and general health status
In the phase 1 portion of the study only, the secondary objective of the study is to assess
the preliminary anti-tumor activity of REGN5459 as measured by ORR.
In the phase 2 portion of the study only, the secondary objective of the study is to evaluate
the safety and tolerability of REGN5459.
Title
- Brief Title: First In Human (FIH) Study of REGN5459 in Adult Patients With Relapsed or Refractory Multiple Myeloma (MM)
- Official Title: Phase 1/2 FIH Study of REGN5459 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma
Clinical Trial IDs
- ORG STUDY ID:
R5459-ONC-1888
- SECONDARY ID:
2019-001108-39
- NCT ID:
NCT04083534
Conditions
- Relapsed Multiple Myeloma
- Refractory Multiple Myeloma
Interventions
Drug | Synonyms | Arms |
---|
REGN5459 | | REGN5459 |
Purpose
In the phase 1 portion of the study, the primary objectives are to assess the safety,
tolerability, and dose-limiting toxicities (DLTs) and to determine a recommended phase 2 dose
regimen (RP2DR) of REGN5459 as monotherapy in patients with relapsed or refractory multiple
myeloma (MM) who have exhausted all therapeutic options that are expected to provide
meaningful clinical benefit.
In the phase 2 portion of the study, the primary objective is to assess the preliminary
anti-tumor activity of REGN5459 as measured by objective response rate (ORR).
In the phase 1 and phase 2 portion, the secondary objectives of the study are:
- To assess the preliminary anti-tumor activity of REGN5459 as measured by duration of
response (DOR), progression-free survival (PFS), rate of minimal residual disease (MRD)
negative status, and overall survival (OS)
- To evaluate the pharmacokinetic (PK) properties of REGN5459
- To characterize the immunogenicity of REGN5459
- To evaluate the effects of REGN5459 on patient-reported quality of life (QoL), symptoms,
functioning and general health status
In the phase 1 portion of the study only, the secondary objective of the study is to assess
the preliminary anti-tumor activity of REGN5459 as measured by ORR.
In the phase 2 portion of the study only, the secondary objective of the study is to evaluate
the safety and tolerability of REGN5459.
Trial Arms
Name | Type | Description | Interventions |
---|
REGN5459 | Experimental | Cohorts of multiple REGN5459 dose levels | |
Eligibility Criteria
Key Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- Patients must have myeloma that is response-evaluable according to the 2016
International Myeloma Working Group (IMWG) response criteria
- Measurable disease is defined as 1 or more of the following:
1. Serum M-protein ≥1 g/dL,
2. Urine M-protein ≥200 mg/24-hour, and/or
3. Free light chain (FLC) assay with involved FLC level ≥10 mg/dL with an abnormal
serum FLC ratio
- A patient with Immunoglobulin A (IgA) myeloma but without measurable M-protein may be
enrolled if quantitative IgA levels are ≥400 mg/dL and can be followed longitudinally
- A patient with non-secretory MM may be considered for enrollment after discussion with
the sponsor that includes the feasibility of an individualized plan for response
assessment
- 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:
1. Progression on or after at least 3 lines of therapy, or intolerance of therapy,
including a proteasome inhibitor, an Immunomodulatory imide drug (IMiD), and an
anti-CD38 antibody, OR
2. Progression on or after an anti-CD38 antibody and having 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. Refractory disease is defined as
lack of response or relapse within 60 days of last treatment.
- Adequate hematologic function as measured by:
1. Platelet count > 50 x 109/L. A patient may not have received a platelet
transfusion within 7 days to meet this platelet eligibility requirement.
2. ANC > 1.0 x 109/L. A patient may not have received granulocyte colony stimulating
factor (G-CSF) within 2 days to meet this absolute neutrophil count eligibility
requirement.
3. Hemoglobin > 8.0 g/dL
- Adequate hepatic function, defined as:
1. Total bilirubin ≤1.5 x ULN
2. Transaminase (ALT, AST) ≤2.5 x ULN
3. Alkaline phosphatase ≤2.5 x ULN
- Patients with Gilbert syndrome do not need to meet this total bilirubin requirement
provided that the total bilirubin is unchanged from the baseline value.
d. Serum creatinine clearance by Cockcroft-Gault >30 mL/min
- A patient with a creatinine clearance by Cockcroft-Gault who does not meet eligibility
criteria may be considered for enrollment if a measured creatinine clearance (based on
24-hour urine collection or other reliable method) is >30 mL/min
- Life expectancy of at least 6 months
Key Exclusion Criteria:
- Patients with known MM brain lesions or meningeal involvement
- History of neurodegenerative condition or central nervous system (CNS) movement
disorder, or patients with a history of seizure within 12 months before study
enrollment are excluded
- Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan
(MUGA)
- Prior treatment with any anti-BCMA antibody (including antibody-drug conjugate or
bispecific antibody) or BCMA-directed CAR T therapy
- Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus
(HBV) or hepatitis C virus (HCV) infection; or other uncontrolled infection
1. Patients with HIV who have controlled infection (undetectable viral load and CD4
count above 350 cells/microliter either spontaneously or on a stable antiviral
regimen) are permitted.
2. Patients with hepatitis B (Hepatitis B Surface Antigen Test positive [HepBsAg+])
who have controlled infection (serum HBV DNA polymerase chain reaction [PCR] that
is below the limit of detection AND receiving anti-viral therapy for hepatitis B)
are permitted.
3. Patients who are HCV antibody-positive (HCV Ab+) who have controlled infection
(undetectable HCV RNA by polymerase chain reaction (PCR) either spontaneously or
in response to a successful prior course of anti-HCV therapy) are permitted.
- History of allogeneic stem cell transplantation at any time, or autologous stem cell
transplantation within 12 weeks of the start of study treatment
NOTE: Other protocol defined Inclusion/Exclusion Criteria apply.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period |
Time Frame: | Up to 35 Days |
Safety Issue: | |
Description: | Phase 1 |
Secondary Outcome Measures
Measure: | Concentrations of REGN5459 in the serum over time |
Time Frame: | Up to 12 Weeks After the Last Dose |
Safety Issue: | |
Description: | Phase 1 and phase 2 |
Measure: | Incidence over time of anti-drug antibodies (ADAs) to REGN5459 |
Time Frame: | Up to 12 Weeks After the Last Dose |
Safety Issue: | |
Description: | Phase 1 and phase 2 |
Measure: | Duration of response (DOR) using the IMWG criteria |
Time Frame: | Up to Approximately 104 Weeks |
Safety Issue: | |
Description: | Phase 1 and phase 2 |
Measure: | Progression-free survival (PFS) as measured using the IMWG criteria |
Time Frame: | Up to Approximately 104 Weeks |
Safety Issue: | |
Description: | Phase 1 and phase 2 |
Measure: | Rate of minimal residual disease (MRD) negative status using the IMWG criteria |
Time Frame: | Up to Approximately 104 Weeks |
Safety Issue: | |
Description: | Phase 1 and phase 2 |
Measure: | Overall survival (OS) |
Time Frame: | Up to Approximately 104 Weeks |
Safety Issue: | |
Description: | Phase 1 and phase 2 |
Measure: | Patient-reported Quality of Life (QOL) per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) |
Time Frame: | Up to 12 Weeks After the Last Dose |
Safety Issue: | |
Description: | Phase 1 and 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." |
Measure: | Patient-reported QOL per EORTC Quality of Life Questionnaire-Multiple Myeloma module 20 (EORTC QLQ-MY20) |
Time Frame: | Up to 12 Weeks After the Last Dose |
Safety Issue: | |
Description: | Phase 1 and 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. |
Measure: | Patient-reported QOL per EuroQoL-5 Dimension-3 Level Scale (EQ-5D-3L) |
Time Frame: | Up to 12 Weeks After the Last Dose |
Safety Issue: | |
Description: | Phase 1 and 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. |
Measure: | Change in patient-reported global health status/QOL per EORTC QLQ-C30 |
Time Frame: | Baseline up to 12 Weeks After the Last Dose |
Safety Issue: | |
Description: | Phase 1 and 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." |
Measure: | Time to definitive deterioration in patient-reported global health status/QOL per EORTC QLQ-C30 |
Time Frame: | Up to 12 Weeks After the Last Dose |
Safety Issue: | |
Description: | Phase 1 and 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." |
Measure: | Change in patient-reported general health status per EQ-5D-3L |
Time Frame: | Baseline up to 12 Weeks After the Last Dose |
Safety Issue: | |
Description: | Phase 1 and 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. |
Measure: | ORR as measured using the IMWG criteria |
Time Frame: | Up to Approximately 104 Weeks |
Safety Issue: | |
Description: | Phase 1 Only |
Measure: | Incidence and severity of TEAEs during REGN5459 treatment period |
Time Frame: | Up to 12 Weeks After the Last Dose |
Safety Issue: | |
Description: | Phase 2 Only |
Measure: | Incidence and severity of AESI during REGN5459 treatment period |
Time Frame: | Up to 12 Weeks After the Last Dose |
Safety Issue: | |
Description: | Phase 2 Only |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Regeneron Pharmaceuticals |
Last Updated
June 15, 2021