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 Odronextamab in Patients With Relapsed or Refractory B-cell Non-Hodgkin 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 B-cell Non-Hodgkin Lymphoma

Clinical Trial IDs

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

Conditions

  • B-cell Non-Hodgkin Lymphoma (NHL)

Interventions

DrugSynonymsArms
OdronextamabREGN1979DLBCL

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
FLExperimentalFollicular lymphoma grade 1-3a cohort
  • Odronextamab
DLBCLExperimentalDiffuse large B-cell lymphoma cohort
  • Odronextamab
MCLExperimentalMantle Cell Lymphoma cohort
  • Odronextamab
MZLExperimentalMarginal Zone Lymphoma cohort
  • Odronextamab
Other B-NHLExperimentalOther B-cell non-Hodgkin lymphoma cohort (excluding FL Grade 1-3a, DLBCL, MCL, MZL, Waldenström macroglobulinemia [WM])
  • Odronextamab

Eligibility Criteria

        Key Inclusion Criteria:

          -  For the FL grade 1-3a cohort only: Central histopathologic confirmation of the FL
             Grade 1 to 3a diagnosis must be obtained before study enrollment. Patients with FL
             grade 3b are ineligible for this cohort but may be included in the "other B-NHL"
             cohort. Follicular lymphoma subtyping is based on the World Health Organization (WHO)
             classification (Swerdlow, 2017).

          -  Disease-specific cohorts that has relapsed after or is refractory to at least 2 prior
             lines of systemic therapy as defined in the protocol

          -  DLBCL cohort: Patients with DLBCL that has relapsed after or is refractory to at least
             2 prior lines of systemic therapy as defined in the protocol

          -  MCL after BTK inhibitor therapy cohort: New enrollment is paused until further notice

          -  MZL cohort: New enrollment is paused until further notice

          -  Other B-NHL cohort: Patients with B-NHL other than FL grade 1-3a, DLBCL, MCL, or MZL
             that has relapsed after or is refractory to at least 2 prior lines of systemic therapy
             as defined in the protocol. New enrollment stopped for patients with Burkitt lymphoma
             and Burkitt-like lymphoma.

          -  Patients should in the judgment of the investigator require systemic therapy for
             lymphoma 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. Patients with a
             history of seizure within 12 months prior to study enrollment are excluded

          -  Another malignancy except B-NHL 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

          -  Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy

        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 (FL grade 1-3a/MZL)
Time Frame:From first patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study
Safety Issue:
Description:For each of the 5 disease-specific cohorts according to the Lugano Classification of response in malignant lymphoma (Cheson, 2014) and as assessed by independent central review.

Secondary Outcome Measures

Measure:ORR (FL/MZL)
Time Frame:First patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study.
Safety Issue:
Description:According to the Lugano Classification, as assessed by local investigator evaluation
Measure:ORR (DLBCL/MCL/Other B-NHL)
Time Frame:First patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study.
Safety Issue:
Description:According to the Lugano Classification, as assessed by local investigator evaluation
Measure:CR rate (FL grade 1-3a/MZL)
Time Frame:First patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study.
Safety Issue:
Description:According to the Lugano Classification and as assessed by local investigator evaluation and independent central review
Measure:CR rate (DLBCL/MCL/Other B-NHL)
Time Frame:First patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study.
Safety Issue:
Description:According to the Lugano Classification and as assessed by local investigator evaluation and independent central review
Measure:PFS
Time Frame:First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Safety Issue:
Description:According to the Lugano Classification and as assessed by independent central review and local investigator evaluation
Measure:OS
Time Frame:First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Safety Issue:
Description:
Measure:DOR
Time Frame:First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Safety Issue:
Description:According to the Lugano Classification and as assessed by independent central review and local investigator evaluation
Measure:DCR (FL grade 1-3a/MZL)
Time Frame:First patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study.
Safety Issue:
Description:According to the Lugano Classification and as assessed by independent central review and local investigator evaluation
Measure:DCR (DLBCL/MCL/Other B-NHL)
Time Frame:First patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study.
Safety Issue:
Description:According to the Lugano Classification and as assessed by independent central review and local investigator evaluation
Measure:Incidence and severity of treatment emergent adverse events (TEAEs)
Time Frame:First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Safety Issue:
Description:
Measure:Pharmacokinetics: Concentration of odronextamab
Time Frame:12 weeks following end of treatment
Safety Issue:
Description:End of infusion [EOI]; Concentration at a specified time t [Ct])
Measure:Immunogenicity: Anti-odronextamab antibodies
Time Frame:12 weeks following end of treatment
Safety Issue:
Description:
Measure:Changes in scores of patient-reported outcomes as measured by EORTC QLQ-C30
Time Frame:First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 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 FACT-Lym
Time Frame:First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Safety Issue:
Description:Composed of the FACT-G plus the 15-item Lymphoma Subscale (LymS).
Measure:Changes in scores of patient-reported outcomes as measured by EQ-5D-3L
Time Frame:First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 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 B-NHL
  • Refractory B-NHL
  • NHL
  • FL
  • DLBCL
  • MZL
  • MCL
  • bispecific antibody
  • CD20

Last Updated

July 27, 2021