Clinical Trials /

Assess the Anti-Tumor Activity and Safety of Odronextamab in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

NCT03888105

Description:

Primary objective is to assess the anti-tumor activity of single agent odronextamab as measured by the objective response rate (ORR) according to the Lugano Classification of response in malignant lymphoma (Cheson, 2014) and as assessed by independent central review in each of the following B-cell non-Hodgkin lymphoma (B-NHL) subgroups: - In patients with follicular lymphoma (FL) grade 1-3a *1,2 - In patients with diffuse large B-cell lymphoma (DLBCL) *1,2 - In patients with mantle cell lymphoma (MCL) that has relapsed after or is refractory to a BTK inhibitor. This cohort will also include patients who have relapsed or have disease refractory to prior systemic therapy, or patients who have demonstrated intolerance to BTK inhibitor therapy, and who have progressed after other systemic therapy. - In patients with marginal zone lymphoma (MZL) *1 - In patients with other B-NHL subtypes *1 Secondary objectives are: - To assess the anti-tumor activity of single agent odronextamab in each of 5 disease-specific cohorts, as measured by: - ORR according to the Lugano Classification and as assessed by local investigator evaluation - Complete response (CR) rate according to the Lugano Classification and as assessed local by local investigator evaluation and independent central review - Progression-free survival (PFS)*3 - Overall survival (OS) - Duration of response (DOR)*3 - Disease control rate (DCR)*3 - To evaluate the safety and tolerability of odronextamab - To assess the pharmacokinetics (PK) of odronextamab - To assess the immunogenicity of odronextamab - To assess the effect of odronextamab on patient reported outcomes, including health-related quality of life (HRQL), as measured by the validated instruments European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym), and EuroQoL 5 Dimensions 3 Levels (EQ-5D-3L) - 1 that has relapsed after or is refractory to at least 2 prior lines of systemic therapy - 2 including an anti-CD20 antibody and an alkylating agent - 3 according to Lugano Classification and as assessed by independent central review and local investigator evaluation

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Assess the Anti-Tumor Activity and Safety of REGN1979 in Patients With Relapsed or Refractory Follicular Lymphoma
  • Official Title: An Open-Label Study to Assess the Anti-Tumor Activity and Safety of REGN1979, an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Patients With Relapsed or Refractory Follicular Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: R1979-ONC-1625
  • SECONDARY ID: 2017-002139-41
  • NCT ID: NCT03888105

Conditions

  • Follicular Lymphoma

Interventions

DrugSynonymsArms
REGN1979REGN1979

Purpose

The primary objective of this study is to assess the anti-tumor activity of single agent REGN1979, as measured by objective response rate (ORR) according to the Lugano Classification of response in malignant lymphoma (Cheson, 2014) by independent central review, in patients with follicular lymphoma (FL) that has relapsed or is refractory to at least 2 prior lines of systemic therapy, including an anti-CD20 antibody and an alkylating agent. The secondary objectives in this study are: - To assess the anti-tumor activity of single agent REGN1979 in patients with relapsed or refractory FL, as measured by: - ORR according to the Lugano Classification (Cheson, 2014) as assessed by local investigator evaluation - Complete response (CR) rate according to the Lugano Classification as assessed by independent central review and local investigator evaluation - Progression-free survival (PFS) according to Lugano Classification as assessed by independent central review and local investigator evaluation - Overall survival (OS) - Duration of response (DOR) according to the Lugano Classification as assessed by independent central review and local investigator evaluation - Disease control rate (DCR) according to the Lugano Classification as assessed by independent central review and local investigator evaluation - Duration of disease control (DDC) according to the Lugano Classification as assessed by independent central review and local investigator evaluation - To evaluate the safety and tolerability of REGN1979 - To assess the pharmacokinetics (PK) of REGN1979 - To assess the immunogenicity of REGN1979 - To assess the effect of REGN1979 on quality of life as measured by the validated instruments European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and EuroQoL 5 Dimensions 3 Levels (EQ-5D-3L)

Trial Arms

NameTypeDescriptionInterventions
REGN1979Experimental
  • REGN1979

Eligibility Criteria

        Key Inclusion Criteria:

          -  Central histopathologic confirmation of the FL Grade 1 to 3a diagnosis must be
             obtained before study enrollment. Patients with FL grade 3b are ineligible. Follicular
             lymphoma subtyping is based on the World Health Organization (WHO) classification
             (Swerdlow, 2017).

          -  Disease must have relapsed or must be refractory to ≥2 prior lines of systemic
             therapy, including an anti-CD20 antibody and an alkylating agent. Patients should in
             the opinion of the investigator require therapy for FL at the time of study
             enrollment.

          -  Measurable disease on cross sectional imaging as defined in the protocol documented by
             diagnostic imaging (computed tomography (CT), or magnetic resonance imaging (MRI))

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Adequate bone marrow, hepatic, and renal function as defined in the protocol

        Key Exclusion Criteria:

          -  Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS
             Non-Hodgkin Lymphoma (NHL) (suspected CNS lymphoma should be evaluated by lumbar
             puncture, as appropriate, in addition to the mandatory head CT or MRI).

          -  Treatment with any systemic anti-lymphoma therapy within 5 half-lives or within 28
             days prior to first administration of study drug, whichever is shorter.

          -  History of allogeneic stem cell transplantation

          -  Prior treatment with any chimeric antigen receptor T-cell (CAR-T) therapy

          -  Continuous systemic corticosteroid treatment with more than 10 mg per day of
             prednisone or anti-inflammatory equivalent within 72 hours of start of study drug

          -  History of neurodegenerative condition or CNS movement disorder

          -  History of uncontrolled seizure disorder, defined as any seizure within 12 months
             prior to study enrollment

          -  Another malignancy except FL in the past 5 years, with the exception of non-melanoma
             skin cancer that has undergone potentially curative therapy or in situ cervical
             carcinoma, or any other tumor that has been deemed to be effectively treated with
             definitive local control and with curative intent.

          -  Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or
             hepatitis C infection; or other uncontrolled infection as defined in the protocol

          -  Known hypersensitivity to both allopurinol and rasburicase

        Note: Other protocol defined Inclusion/Exclusion criteria apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:ORR
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:As measured by the Lugano Classification of response in malignant lymphoma (Cheson, 2014) and according to independent central review, in patients with FL that has relapsed or is refractory to at least 2 prior lines of systemic therapy, including an anti-CD20 antibody and an alkylating agent.

Secondary Outcome Measures

Measure:ORR
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:According to the Lugano Classification, as assessed by local investigator evaluation
Measure:CR rate
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:According to the Lugano Classification, as assessed by independent central review
Measure:CR rate
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:According to the Lugano Classification, as assessed by local investigator evaluation
Measure:PFS
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:According to the Lugano Classification, as assessed by independent central review
Measure:PFS
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:According to the Lugano Classification, as assessed by local investigator evaluation
Measure:OS
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:
Measure:DOR
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:According to the Lugano Classification, as assessed by independent central review
Measure:DOR
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:According to the Lugano Classification, as assessed by local investigator evaluation
Measure:DCR
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:According to the Lugano Classification, as assessed by independent central review
Measure:DCR
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:According to the Lugano Classification, as assessed by local investigator evaluation
Measure:DDC
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:According to the Lugano Classification, as assessed by independent central review
Measure:DDC
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:According to the Lugano Classification, as assessed by local investigator evaluation
Measure:Incidence and severity of treatment emergent adverse events (TEAEs)
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:
Measure:Changes in scores of patient-reported outcomes as measured by EORTC QLQ-C30
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:EORTC QLQ-C30 is a self-reported, 30-item generic questionnaire developed to assess 15 domains: global health status scale, five functional scales (physical, role, emotional, cognitive, and social functioning) and nine symptom scales (fatigue, nausea, vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties).
Measure:Changes in scores of patient-reported outcomes as measured by EQ-5D-3L
Time Frame:From first dose until 194 weeks following the first dose
Safety Issue:
Description:The EQ-5D-3L is a standardized instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Regeneron Pharmaceuticals

Trial Keywords

  • Relapsed
  • Refractory

Last Updated

November 22, 2019