Phase 1/2 FIH Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma

The primary objectives of the study are:

Phase 1: 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 therapeutic options

Phase 2: To assess the preliminary anti-tumor activity of REGN5458

The secondary objectives of the study are:

  • To evaluate the pharmacokinetic (PK) properties of REGN5458
  • To characterize the immunogenicity of REGN5458
  • To assess the preliminary anti-tumor activity of REGN5458 (Phase 1)
  • To evaluate the safety and tolerability of REGN5458 (Phase 2)
  • To evaluate the correlation between the activity of REGN5458 and PK (Phase 2)

June 13, 2019
Cancer, Multiple Myeloma, Cancer (Hematology) - Multiple Myeloma / Plasma Cell Malignancies
William Bensinger, M.D.

Swedish Cancer Institute

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 symptomatic myeloma at the time of study entry with myeloma-related organ damage or tissue dysfunction
  • Patients must have myeloma that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chain (FLC)
  • A patient with non-secretory MM may be considered for enrollment after discussion with the sponsor that includes the feasibility of the plan for response assessment according to IMWG guidelines
  • Disease progression based on IMWG criteria
  • Patients with MM who have exhausted all therapeutic options known to provide clinical benefit, either through disease relapse or intolerance or refusal 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.
  • Adequate hematologic and hepatic function
  • Serum creatinine clearance by Cockcroft-Gault >30 mL/min

Key Exclusion Criteria:

  • Presence of plasma cell leukemia, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Patients with known MM brain lesions or meningeal involvement with MM
  • History of neurodegenerative condition or central nervous system movement disorder
  • Continuous systemic corticosteroid treatment with more than 10 mg of prednisone or equivalent per day
  • Treatment with any systemic standard or investigational anti-myeloma therapy within 5 half-lives or within 28 days prior to 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 (HBV) or hepatitis C (HCV) infection; or other uncontrolled infection
  • A severe allergic reaction is defined for this purpose as that which has met criteria for CTCAE v5 Grade 3 or Grade 4 severity (ie, characterized by bronchospasm; or life-threatening consequences; or requiring intravenous 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 unwilling to practice highly effective contraception during the study

Note: Other protocol defined inclusion / exclusion criteria apply


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