LINKER-MM1: First in Human (FIH) Study of REGN5458 in Patients With Relapsed or Refractory Multiple Myeloma
Study Details
Study Description
Brief Summary
The primary objectives of the study are:
In the phase 1 portion of the study: To assess the safety, tolerability, and dose-limiting toxicities (DLTs) and to determine one or more recommended phase 2 dose regimens (RP2DRs) of REGN5458 as monotherapy in patients with relapsed or refractory multiple myeloma (MM).
In the phase 2 portion of the study: To assess the anti-tumor activity of REGN5458 separately in cohorts 1 and 2, as measured by objective response rate (ORR) and as determined by an Independent Review Committee (IRC) in patients who have progressed on or after 3 prior lines of therapy or who are triple-refractory (defined as refractory to a(n) proteasome inhibitor (PI), immunomodulatory imide (IMiD) drug (s), and anti-cluster of differentiation 38 (anti-CD38) monoclonal antibody).
The secondary objectives of the study are:
In the phase 1 dose escalation portion:
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To assess the preliminary anti-tumor activity of REGN5458 as determined by the investigator and measured by ORR, duration of response (DOR), progression-free survival (PFS), rate of minimal residual disease (MRD) negative status, and overall survival (OS)
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To evaluate the pharmacokinetic (PK) properties of REGN5458
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To characterize the immunogenicity of REGN5458
In the phase 2 for each cohort:
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To assess the anti-tumor activity of REGN5458 as measured by: ORR, DOR, PFS, as determined by an IRC and the investigator, rate of MRD negative status and OS
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To evaluate the effects of REGN5458 on health-related quality of life (HRQoL) and patient-reported functions and symptoms
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To evaluate the safety and tolerability of REGN5458
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To evaluate the PK properties of REGN5458
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To characterize the immunogenicity of REGN5458
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: REGN5458 Phase 1: Cohorts of multiple REGN5458 dose levels Phase 2: Until disease progression or other discontinuation criterion is met |
Drug: REGN5458
Administered by intravenous (IV) infusion
|
Outcome Measures
Primary Outcome Measures
- Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period [Up to 28 days]
In the phase 1 portion
- Incidence and severity of treatment-emergent adverse events (TEAEs) [Up to 5 years]
In the phase 1 portion
- Incidence and severity of adverse events of special interest (AESI) [Up to 5 years]
In the phase 1 portion
- Objective response rate (ORR) as measured using the International Myeloma Working Group (IMWG) criteria [Up to 5 years]
In the phase 2 portion Determined by blinded Independent Review Committee (IRC).
Secondary Outcome Measures
- Concentrations of REGN5458 in the serum over time [Up to 5 years]
In the phase 1 and phase 2 portions
- Incidence over time of anti-drug antibodies (ADAs) to REGN5458 [Up to 5 years]
In the phase 1 and Phase 2 portions
- Duration of response (DOR) using the IMWG criteria [Up to 5 years]
In the phase 1 and Phase 2 portions
- Progression-free survival (PFS) as measured using the IMWG criteria [Up to 5 years]
In the phase 1 and Phase 2 portions
- Rate of minimal residual disease (MRD) negative status using the IMWG criteria [Up to 5 years]
In the phase 1 and Phase 2 portions
- Overall survival (OS) [Up to 5 years]
In the phase 1 and Phase 2 portions
- ORR as measured using the IMWG criteria [Up to 5 years]
In the phase 1 and Phase 2 portions As determined by the Investigator
- Effects of REGN5458 on 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]
In the phase 2 portion 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."
- 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]
In the phase 2 portion 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.
- 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]
In the phase 2 portion 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.
- Change in patient-reported global health status/QoL per EORTC QLQ-C30 [Baseline up to Up to 5 years]
In the phase 2 portion
- Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30 [Up to 5 years]
In the phase 2 portion
- Effects of REGN5458 on general health status per EQ-5D-3L [Up to 5 years]
In the phase 2 portion
- Effects of REGN5458 on patient-reported functions and symptoms per EORTC QLQ-C30 [Up to 5 years]
In the phase 2 portion
- Effects of REGN5458 on patient-reported functions and symptoms per QLQ-MY20 [Up to 5 years]
In the phase 2 portion
- Incidence and severity of TEAEs with REGN5458 [Up to 5 years]
In the phase 2 portion
- Incidence and severity of AESIs with REGN5458 [Up to 5 years]
In the phase 2 portion
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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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 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:
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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
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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. Refractory disease is defined as lack of response or relapse within 60 days of last treatment.
Phase 2:
- 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. In addition, patients must be penta-exposed (ie, having prior exposure to 2 PIs, 2 IMiDs [lenalidomide and pomalidomide], and 1 anti-CD38 monoclonal antibody).
Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or less than 25% response to therapy.
Key Exclusion Criteria:
-
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)
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Patients with known MM brain lesions or meningeal involvement
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Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific antibodies and BiTEs, and BCMA CAR T cells. Note: BCMA antibody-drug conjugates are not excluded
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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: Other protocol defined inclusion / exclusion criteria apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Miami Hospital/Sylvester Comprehensive | Miami | Florida | United States | 33136 |
| 2 | Moffitt Cancer Center | Tampa | Florida | United States | 33612 |
| 3 | Winship Cancer Institute of Emory University | Atlanta | Georgia | United States | 30322 |
| 4 | Indiana University Melvin and Bren Simon Comprehensive Cancer Center | Indianapolis | Indiana | United States | 46202 |
| 5 | Norton Cancer Institute | Louisville | Kentucky | United States | 40207 |
| 6 | University of Michigan Health System | Ann Arbor | Michigan | United States | 48109 |
| 7 | Barbara Ann Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 8 | Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey | United States | 08901 |
| 9 | The Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
| 10 | Columbia University Medical Center, Herbert Irving Pavilion | New York | New York | United States | 10032-3729 |
| 11 | The Ohio State University, James Cancer Hospital | Columbus | Ohio | United States | 43210 |
| 12 | Oregon Health Science University OHSU | Portland | Oregon | United States | 97239 |
| 13 | University of Texas MD Anderson Clinic | Houston | Texas | United States | 77030 |
| 14 | Swedish Cancer Institute | Seattle | Washington | United States | 98104 |
| 15 | Ziekenhuis Netwerk Antwerpen (ZNA)- Stuivenberg | Antwerp | Belgium | 2060 | |
| 16 | Cliniques Universitaires Saint-Luc | Brussels | Belgium | 1200 | |
| 17 | Universitaetsklinikum Essen | Essen | Germany | 45147 | |
| 18 | University Medicine Mainz | Mainz | Germany | 55131 | |
| 19 | Universitatsklinikum Wurzburg | Würzburg | Germany | 6 97080 | |
| 20 | National Cancer Center | Goyang-si | Gyeonggi-do | Korea, Republic of | 10408 |
| 21 | Soul National University Hospital Jongno-gu | Seoul | Korea, Republic of | 03080 | |
| 22 | Severance Hospital, Yonsei University Health System Seodaemun-gu | Seoul | Korea, Republic of | 03722 | |
| 23 | Seoul St.Mary's Hospital, The Catholic University of Korea Seocho-gu | Seoul | Korea, Republic of | 06591 | |
| 24 | Hospital Universitario Sant Pau, Carrer de Sant Antoni Maria Claret, 167 | Barcelona | Spain | 08025 | |
| 25 | Hospital Universitario Ramon y Cajal M-607, km 9.100 | Madrid | Spain | 28034 | |
| 26 | Hospital 12 de Octubre Avda de Cordoba, s/n | Madrid | Spain | 28041 | |
| 27 | Hospital Universitario de Salamanca Paseo de San Vicente 58-182 | Salamanca | Spain | 37007 |
Sponsors and Collaborators
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Trial Management, Regeneron Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R5458-ONC-1826
- 2018-003188-78