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

Trial number:
NCT03888105
Trial phase:
2
Study type:
Immunotherapy, Targeted therapy
Overall status:
Recruiting

Study start date

November, 2019

Scientific 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

Summary

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

Key

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

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; cytomegalovirus (CMV) infection as noted by detectable levels on a blood polymerase chain reaction (PCR) assay as defined in the protocol or other uncontrolled infections 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

Study design

Primary purpose: Treatment, Allocation: Non-Randomized, Intervention model: Parallel Assignment, Intervention model description: 5 cohorts The first 68 patients in the DLBCL cohort will be randomized; the remaining patients will not be randomized, Masking: None (Open Label),

Conditions

B-cell Non-Hodgkin Lymphoma (NHL)

Other study ID numbers

R1979-ONC-1625; 2017-002139-41

Choose trial site (338)

National University Hospital 119074
National University Hospital 119074 Recruiting
Singapore 119074
Farrer Park
Farrer Park Recruiting
Singapore 217562
Taipei Medical University Hospital Recruiting