B-cell malignancies MedDRA version: 21.0 Level: PT Classification code 10003903 Term: B-cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10003917 Term: B-cell type acute leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10026945 Term: Mature B-cell type acute l
Conditions
Interventions
Product Name: REGN2810
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Cemiplimab
CAS Number: N/A
Current Sponsor code: REGN2810
Other descriptive name: anti-PD-1 monoclonal antibody
C
Sponsors
Regeneron Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1-Principal Inclusion Criteria for B-NHL and HL Treatment Arms: Hematologic malignancy defined by either: a. NHL: Documented CD20+ B-cell malignancy, with active disease that is either refractory to or relapsed after most recent prior therapy, for whom no standard of care options exist, and for whom treatment with an anti-CD20 antibody may be appropriate: i. B-NHL per WHO 2008 criteria (Campo 2011) b. Documented HL, per WHO 2008 criteria (Campo 2011), with active disease not responsive to prior therapy or relapsed after prior therapy for whom no standard of care options exist (cemiplimab single agent therapy cohorts ONLY) All patients must have at least one bi-dimensionally measurable lesion (=1.5 cm) documented by diagnostic imaging (CT, PET-CT, or MRI). Eastern Cooperative Oncology Group (ECOG) performance status =1. Note: Individual cases of patients with ECOG 2 performance status may be discussed with the medical monitor for potential enrollment. Age =18 years Adequate bone marrow function documented by: a. Platelet counts =75 x 109/L b. Hb level =9 g/dL c. ANC =1 x 109/L Adequate hepatic function: a. Total bilirubin =1.5 x ULN (=3 x ULN if liver involvement) b. Transaminases =2.5 x ULN (=5 x ULN if liver involvement) c. Alkaline phosphatase (ALP) =2.5 x ULN (=5 x ULN if liver involvement) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 86 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 86
Exclusion criteria
Exclusion criteria: 1-Principal Exclusion Criteria for B-NHL and HL Treatment Arms Primary central nervous system (CNS) lymphoma, or known or suspected CNS involvement by non-primary CNS NHL History of or current relevant CNS pathology Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for iAEs History of treatment-related iAEs from immune-modulatory agents Standard or investigational anti-neoplastic therapy (nonbiologic) within 5-times the half life or within 28 days, whichever is shorter, prior to first administration of study drug Standard radiotherapy within 14 days of first administration of study drug Treatment with alemtuzumab within 12 weeks prior to first administration of study drug(s) Treatment with rituximab, immune-modulating agents or other investigational or commercial biologic agent less than 28 days prior to first administration of study drug(s). Prior allogeneic stem cell transplantation Prior treatment with an agent that blocks the PD-1/PD-L1 pathway, unless the patient demonstrated benefit (applicable only for patients in single-agent REGN2810 therapy) Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; or other uncontrolled infection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to assess safety, tolerability and dose limiting toxicity (DLT) of: • Single-agent REGN2810 in patients with lymphoma (B-cell non-Hodgkin lymphoma [B-NHL] and Hodgkin's lymphoma [HL]) • Combination REGN1979 and REGN2810 in patients with B NHL ;Secondary Objective: The secondary objectives of the study are: • To determine a recommended dose for: o cemiplimab as a single-agent in patients with lymphoma (B-NHL and HL) o REGN1979 and cemiplimab administered in combination in patients with B-NHL. • To characterize the pharmacokinetic (PK) profile of cemiplimab when administered as a single agent and of cemiplimab and REGN1979 when administred in combination • To assess the immunogenicity of cemiplimab when administered alone and the immunogenicity of cemiplimab and REGN1979 when administred in combination • To study the preliminary antitumor activity of cemiplimab as a single agent and of the combination of cemiplimab and REGN1979 in specific indications, as measured by overall response rate, minimal residual disease (MRD) in patients with bone marrow disease at baseline, duration of response and median progression-free survival and rates at 6 and 12 months;Primary end point(s): Safety;Timepoint(s) of evaluation of this end point: From informed consent form signature until 30 day post last dose of study drug | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • PK of single agent cemiplimab , and PK of REGN1979 and cemiplimab when given in combination • Antitumor activity: o Overall response rate (ORR) as per applicable response criteria for the indication o Duration of response, and PFS at 6 and 12 months o Minimal residual disease (MRD) for patients with bone marrow involvement at baseline • Pharmacodynamic measures including: o Cytokine profiling o Peripheral blood B-cell and T-cell subsets and immune phenotyping o Analysis of PD-1 receptor occupancy of circulating T-cells o Changes in gene expression in peripheral blood o Serum immunoglobulin ;Timepoint(s) of evaluation of this end point: each of the secondary endpoints is being assessed at specific time points as outlined in protocol | — |
Countries
Germany, Spain, United States
Contacts
Public ContactClinical Trial Management
Regeneron Pharmaceuticals, Inc.
Outcome results
None listed