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
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
Drug | Synonyms | Arms |
---|
Odronextamab | REGN1979 | DLBCL |
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
Name | Type | Description | Interventions |
---|
FL | Experimental | Follicular lymphoma grade 1-3a cohort | |
DLBCL | Experimental | Diffuse large B-cell lymphoma cohort | |
MCL | Experimental | Mantle Cell Lymphoma cohort | |
MZL | Experimental | Marginal Zone Lymphoma cohort | |
Other B-NHL | Experimental | Other B-cell non-Hodgkin lymphoma cohort (excluding FL Grade 1-3a, DLBCL, MCL, MZL, Waldenström macroglobulinemia [WM]) | |
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