Relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) MedDRA version: 22.0 Level: PT Classification code 10029547 Term: Non-Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: REGN1979
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Odronextamab
Current Sponsor code: REGN1979
Other descriptive name: REGN1979
Concentration unit:
Sponsors
Regeneron Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The enrolment of all patients with B-cell malignancies is paused as of protocol amendment EU4 •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: • FL grade 1-3a cohort: Patients with FL grade 1-3a 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: Not currently enrolling patients with mantle cell lymphoma (MCL) as of Global Amendment 3 • MZL cohort: Patients with MZL that has relapsed after or is refractory to at least 2 prior lines of systemic therapy as defined in the protocol. • 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. • Patients should in the judgment of the investigator require systemic therapy for lymphoma at the time of study enrollment and deemed not appropriate for any other approved therapy with established benefit for that indication • 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 Note: Other protocol defined Inclusion criteria apply 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 193 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 288
Exclusion criteria
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 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 Exclusion criteria apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the anti-tumor activity of single agent odronextamab as measured by the ORR according to the Lugano Classification of response in malignant lymphoma 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 *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;Secondary Objective: 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 EORTC QLQ-C30, FACT-Lym, and EQ-5D-3L *3 according to Lugano Classification and as assessed by independent central review and local investigator evalua | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints for each of the 5 disease-specific cohorts include: 1: ORR according to the Lugano Classification and as assessed by local investigator evaluation 2: Complete response (CR) rate according to the Lugano Classification and as assessed by local investigator evaluation and independent central review. 3: Progression free survival (PFS) according to the Lugano Classification and as assessed by independent central review and local investigator evaluation 4: Overall survival (OS) 5: Duration of response (DOR) according to the Lugano Classification and as assessed by independent central review and local investigator evaluation 6: Disease control rate (DCR) according to the Lugano Classification and as assessed by independent central review and local investigator evaluation by independent central review and local investigator evaluation 7: Incidence and severity of treatment emergent adverse events (TEAEs) 8: Pharmacokinetics (Concentration of odronextamab; End of infusion [EOI]; Concentration at a specified time t [Ct]) 9: Immunogenicity (Anti-odronextamab antibodies) 10: Changes in scores of patient-reported outcomes as measured by EORTC QLQ-C30 11: Changes in scores of patient-reported outcomes as measured by FACT-Lym 12: Changes in scores of patient-reported outcomes as measured by EQ-5D-3L;Timepoint(s) of evaluation of this end point: #1,2, 6: First patient first dose until all patients have completed 28 weeks of study treatment or have withdrawn from the study. #3-5, 7, 10-12: First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose #8-9: 12 weeks following end of treatment | — |
Countries
Australia, Canada, France, Germany, Italy, Korea, Democratic People's Republic of, Poland, Singapore, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Regeneron Pharmaceuticals, Inc.
Outcome results
None listed