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Clinical Trial 20113

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT03761108

Phase: Phase I
Prinicipal Investigator: Jason Brayer

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Overview

Study Title

Phase 1/2 FIH Study of Regn5458 (Anti-BCMA X Anti-CD3 Bispecific Antibody) in Patients with Relapsed or Refractory Multiple Myeloma

Summary

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) who have exhausted all therapeutic options that are expected to provide meaningful clinical benefit. The determination of the RP2DR will be based on the review of non-clinical and all clinical data, including that pertaining to safety, pharmacokinetics (PK), PK/PD (pharmacokinetic/pharmacodynamic) relationships, and efficacy. In the Phase 2 portion of the study: To assess the preliminary anti-tumor activity of REGN5458 as measured by objective response rate (ORR)

Objective

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) (defined as either a maximum tolerated dose regimen [MTDR] or biologically effective dose regimen [BEDR]) of REGN5458 as monotherapy in patients with relapsed or refractory multiple myeloma (MM) who have exhausted therapeutic options. In the Phase 2 portion of the study: To assess the preliminary anti-tumor activity of REGN5458

Treatments

Therapies

Medications

REGN5458 ()

Inclusion Criteria

Inclusion Criteria

  • Eastern Cooperative Oncology Group (ECOG) performance status greater than or equal to 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 must have measurable serum or urine markers as defined by the 2016 IMWG response criteria. Phase 2: patients must have measurable serum or urine markers as defined by the 2016 IMWG response criteria. Up to 20 patients are to be enrolled with measurable extra-medullary plasmacytomas. All other patients must not have measurable extra-medullary plasmacytomas.
  • 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:
  • 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
  • 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 have had prior exposure to bortezomib, lenalidomide, carfilzomib, a CD38 monoclonal antibody and pomalidomide (ie, penta-exposed). Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or less than 25% response to therapy
  • Adequate hematologic and hepatic function
  • Serum creatinine clearance by Cockcroft-Gault >30 mL/min
  • If previously treated with CAR T therapy or any gene therapy products, patient must have recovered from the toxicities of this therapy.
  • Other criteria apply

  • Exclusion Criteria

    Exclusion Criteria:

  • Diagnosis of plasma cell leukemia, amyloid light-chain 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
  • History of neurodegenerative condition, central nervous system (CNS) movement disorder, or patient with a history of seizure within 12 months prior to study enrollment are excluded.
  • Continuous systemic corticosteroid treatment with more than 10 mg of prednisone or anti-inflammatory equivalent within 72 hours of start of study drug
  • Treatment with any systemic standard or investigational anti-myeloma therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter.
  • 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
  • A severe allergic reaction is defined for this purpose as that which has met criteria for common terminology criteria for adverse events (CTCAE) v5.0 grade 3 or grade 4 severity (ie, characterized by bronchospasm; or life-threatening consequences; or requiring intravenous (IV) intervention, other urgent intervention, or hospitalization for clinical sequelae) or that has required an emergency room visit.
  • History of allogeneic stem cell transplantation at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment
  • Known hypersensitivity to both allopurinol and rasburicase
  • Pregnant or breastfeeding women
  • Women of childbearing potential and men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose.
  • Note: Other protocol defined inclusion / exclusion criteria apply

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