A Study to Assess the Anti-Tumor Activity and Safety of Odronextamab in Patients With B-cell Non-Hodgkin Lymphoma That Have Been Previously Treated (ELM-2)

• ClinicalTrials.gov Identifier: NCT03888105
• Recruitment Status: Recruiting
• First Posted: March 25, 2019
• Last Update Posted: April 8, 2024
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: March 14, 2019
• First Posted Date: March 25, 2019
• Last Update Posted Date: April 8, 2024
• Actual Study Start Date: November 13, 2019
• Estimated Primary Completion Date: December 19, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 29, 2021)

• 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[ Time Frame: From first patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study ]
  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.
• ORR (DLBCL/MCL/Other B-NHL) [ Time Frame: From first patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study ]
  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.

Original Primary Outcome Measures (submitted: March 20, 2019)

ORR [ Time Frame: From first dose until 194 weeks following the first dose ]

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.

Current Secondary Outcome Measures (submitted: May 4, 2022)

• 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(FL/MZL) [ Time Frame: First patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study. ]
  According to the Lugano Classification, as assessed by local investigator evaluation
• 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B-NHL) [ Time Frame: First patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study. ]
  According to the Lugano Classification, as assessed by local investigator evaluation
• 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. ]
  According to the Lugano Classification and as assessed by local investigator evaluation and independent central review
• 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. ]
  According to the Lugano Classification and as assessed by local investigator evaluation and independent central review
• 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 ]
  According to the Lugano Classification and as assessed by independent central review and local investigator evaluation
• 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 ]
• 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 ]
  According to the Lugano Classification and as assessed by independent central review and local investigator evaluation
• 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. ]
  According to the Lugano Classification and as assessed by independent central review and local investigator evaluation
• 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. ]
  According to the Lugano Classification and as assessed by independent central review and local investigator evaluation
• 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 ]
• Pharmacokinetics: Concentration of odronextamab [ Time Frame: 12 weeks following end of treatment ]
  End of infusion [EOI]; Concentration at a specified time t [Ct])
• Incidence of anti-drug antibodies (ADA) to odronextamab over time [ Time Frame: 12 weeks following end of treatment ]
• Titer of anti-drug antibodies to odronextamab over time [ Time Frame: 12 weeks following end of treatment ]
• Incidence of neutralizing antibodies (Nab) to odronextamab over time [ Time Frame: 12 weeks following end of treatment ]
• 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 ]
  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).
• 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 ]
  Composed of the FACT-G plus the 15-item Lymphoma Subscale (LymS).
• 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 ]
  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.

Original Secondary Outcome Measures (submitted: March 20, 2019)

• ORR [ Time Frame: From first dose until 194 weeks following the first dose ]
  According to the Lugano Classification, as assessed by local investigator evaluation
• CR rate [ Time Frame: From first dose until 194 weeks following the first dose ]
  According to the Lugano Classification, as assessed by independent central review
• CR rate [ Time Frame: From first dose until 194 weeks following the first dose ]
  According to the Lugano Classification, as assessed by local investigator evaluation
• PFS [ Time Frame: From first dose until 194 weeks following the first dose ]
  According to the Lugano Classification, as assessed by independent central review
• PFS [ Time Frame: From first dose until 194 weeks following the first dose ]
  According to the Lugano Classification, as assessed by local investigator evaluation
• OS [ Time Frame: From first dose until 194 weeks following the first dose ]
• DOR [ Time Frame: From first dose until 194 weeks following the first dose ]
  According to the Lugano Classification, as assessed by independent central review
• DOR [ Time Frame: From first dose until 194 weeks following the first dose ]
  According to the Lugano Classification, as assessed by local investigator evaluation
• DCR [ Time Frame: From first dose until 194 weeks following the first dose ]
  According to the Lugano Classification, as assessed by independent central review
• DCR [ Time Frame: From first dose until 194 weeks following the first dose ]
  According to the Lugano Classification, as assessed by local investigator evaluation
• DDC [ Time Frame: From first dose until 194 weeks following the first dose ]
  According to the Lugano Classification, as assessed by independent central review
• DDC [ Time Frame: From first dose until 194 weeks following the first dose ]
  According to the Lugano Classification, as assessed by local investigator evaluation
• Incidence and severity of treatment emergent adverse events (TEAEs) [ Time Frame: From first dose until 194 weeks following the first dose ]
• 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 ]
  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).
• 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 ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Assess the Anti-Tumor Activity and Safety of Odronextamab in Patients With B-cell Non-Hodgkin Lymphoma That Have Been Previously Treated
• 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

Brief 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

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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)
Primary Purpose: Treatment

• Condition: B-cell Non-Hodgkin Lymphoma (NHL)

Intervention

Drug: Odronextamab

Administered by intravenous (IV) infusion

Other Name: REGN1979

Study Arms

• Experimental: FL
  Follicular lymphoma grade 1-3a cohort
  Intervention: Drug: Odronextamab
• Experimental: DLBCL
  Diffuse large B-cell lymphoma cohort
  Intervention: Drug: Odronextamab
• Experimental: MCL
  Mantle Cell Lymphoma cohort
  Intervention: Drug: Odronextamab
• Experimental: MZL
  Marginal Zone Lymphoma cohort
  Intervention: Drug: Odronextamab
• Experimental: Other B-NHL
  Other B-cell non-Hodgkin lymphoma cohort (excluding FL Grade 1-3a, DLBCL, MCL, MZL, Waldenström macroglobulinemia [WM]); Patients with a current diagnosis of mixed histology of B-NHL with an aggressive component (such as concurrent FL and DLBCL) will be allowed
  Intervention: Drug: Odronextamab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 29, 2021): 512
• Original Estimated Enrollment (submitted: March 20, 2019): 112
• Estimated Study Completion Date: February 5, 2028
• Estimated Primary Completion Date: December 19, 2025 (Final data collection date for primary outcome measure)

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: Patients with MZL that have relapsed or is refractory to at least 2 prior lines of systemic therapy.
• 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; 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

• Listed Location Countries: Australia, Canada, China, France, Germany, Italy, Japan, Korea, Republic of, Poland, Singapore, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT03888105
• Other Study ID Numbers: R1979-ONC-1625; 2017-002139-41 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency [EMA], Pharmaceuticals and Medical Devices Agency [PMDA], etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• URL: https://vivli.org/

• Current Responsible Party: Regeneron Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Regeneron Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: March 2024