First in Human (FIH) Study of REGN5458 in Patients With Relapsed or Refractory Multiple Myeloma

Sponsor
Regeneron Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03761108
Collaborator
(none)
292
Enrollment
15
Locations
1
Arm
75.2
Anticipated Duration (Months)
19.5
Patients Per Site
0.3
Patients Per Site Per Month

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 a recommended phase 2 dose regimen (RP2DR) 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 as measured by objective response rate (ORR) and as determined by an Independent Review Committee (IRC)

The secondary objectives of the study are:
In the phase 1 dose escalation portion:
  • 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)

  • To evaluate the pharmacokinetic (PK) properties of REGN5458

  • To characterize the immunogenicity of REGN5458

In the phase 2:
  • 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

  • To evaluate the effects of REGN5458 on health-related quality of life (HRQoL) and patient-reported functions and symptoms

  • To evaluate the safety and tolerability of REGN5458

  • To evaluate the PK properties of REGN5458

  • To characterize the immunogenicity of REGN5458

Condition or DiseaseIntervention/TreatmentPhase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
292 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1/2 FIH Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date :
Jan 23, 2019
Anticipated Primary Completion Date :
May 1, 2025
Anticipated Study Completion Date :
May 1, 2025

Arms and Interventions

ArmIntervention/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

  1. 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

  2. Incidence and severity of treatment-emergent adverse events (TEAEs) [Up to 5 years]

    In the phase 1 portion

  3. Incidence and severity of adverse events of special interest (AESIs) [Up to 5 years]

    In the phase 1 portion

  4. 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

  1. Concentrations of REGN5458 in the serum over time [Up to 5 years]

    In the phase 1 and phase 2 portions

  2. Incidence over time of anti-drug antibodies (ADAs) to REGN5458 [Up to 5 years]

    In the phase 1 and Phase 2 portions

  3. Duration of response (DOR) using the IMWG criteria [Up to 5 years]

    In the phase 1 and Phase 2 portions

  4. Progression-free survival (PFS) as measured using the IMWG criteria [Up to 5 years]

    In the phase 1 and Phase 2 portions

  5. Rate of minimal residual disease (MRD) negative status using the IMWG criteria [Up to 5 years]

    In the phase 1 and Phase 2 portions

  6. Overall survival (OS) [Up to 5 years]

    In the phase 1 and Phase 2 portions

  7. ORR as measured using the IMWG criteria [Up to 5 years]

    In the phase 1 and Phase 2 portions As determined by the Investigator

  8. 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."

  9. 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.

  10. 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.

  11. Change in patient-reported global health status/QoL per EORTC QLQ-C30 [Baseline up to Up to 5 years]

    In the phase 2 portion

  12. Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30 [Up to 5 years]

    In the phase 2 portion

  13. Effects of REGN5458 on general health status per EQ-5D-3L [Up to 5 years]

    In the phase 2 portion

  14. Effects of REGN5458 on patient-reported functions and symptoms per EORTC QLQ-C30 [Up to 5 years]

    In the phase 2 portion

  15. Effects of REGN5458 on patient-reported functions and symptoms per QLQ-MY20 [Up to 5 years]

    In the phase 2 portion

  16. Incidence and severity of TEAEs with REGN5458 [Up to 5 years]

    In the phase 2 portion

  17. Incidence and severity of AESIs with REGN5458 [Up to 5 years]

    In the phase 2 portion

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

  • Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria

  • Patients must have myeloma that is response-evaluable according to the 2016 IMWG response criteria.

  • 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:

  1. 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

  2. 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)

  • Patients with known MM brain lesions or meningeal involvement

  • 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

  • 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

SiteCityStateCountryPostal Code
1Regeneron Study SiteMiamiFloridaUnited States33136
2Regeneron Study SiteTampaFloridaUnited States33612
3Regeneron Study SiteAtlantaGeorgiaUnited States30322
4Regeneron Study SiteIndianapolisIndianaUnited States46202
5Regeneron Study SiteLouisvilleKentuckyUnited States40207
6Regeneron Study SiteAnn ArborMichiganUnited States48109
7Regeneron Study SiteDetroitMichiganUnited States48201
8Regeneron Study SiteNew BrunswickNew JerseyUnited States08901
9Regeneron Study SiteNew YorkNew YorkUnited States10029
10Regeneron Study SiteNew YorkNew YorkUnited States10032-3729
11Regeneron Study SiteColumbusOhioUnited States43210
12Regeneron Study SiteHoustonTexasUnited States77030
13Regeneron Study SiteSeattleWashingtonUnited States98104
14Regeneron Study SiteAntwerpBelgium2060
15Regeneron Study SiteBrusselsBelgium1200

Sponsors and Collaborators

  • Regeneron Pharmaceuticals

Investigators

  • Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT03761108
Other Study ID Numbers:
  • R5458-ONC-1826
  • 2018-003188-78
First Posted:
Dec 3, 2018
Last Update Posted:
Oct 15, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Regeneron Pharmaceuticals
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 15, 2021