ATHENA-1: Study to Assess the Safety and Tolerability of REGN5837 in Combination With Odronextamab in Patients With Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
The primary objective of the study is:
To assess the safety, tolerability, and dose-limiting toxicities (DLTs) and to determine recommended phase 2 dose (RP2D) regimen(s) (defined as either a maximum tolerated dose (MTD) regimen or a lower dose regimen) of REGN5837 in combination with odronextamab in patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (B-NHL)
The secondary objectives of the study are:
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To evaluate the pharmacokinetics (PK) of REGN5837 when given in combination with odronextamab
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To evaluate the PK of odronextamab when given in combination with REGN5837
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To assess the immunogenicity of REGN5837 and odronextamab
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To assess the preliminary anti-tumor activity of REGN5837 in combination with odronextamab in patients with relapsed or refractory aggressive B-NHL
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Odronextamab and REGN5837 Odronextamab and REGN5837 will be administered by IV infusion using a step-up dosing schedule. |
Drug: Odronextamab
Odronextamab will be administered by IV infusion
Other Names:
Drug: REGN5837
REGN5837 will be administered by IV infusion
|
Outcome Measures
Primary Outcome Measures
- Incidence of Dose Limiting Toxicities (DLTs) of REGN5837 in combination with odronextamab [From Cycle 2, Day 15 to Cycle 4, Day 7 (each induction cycle is 21 days)]
A DLT is defined as any non-haematologic and haematologic toxicity, as defined in the protocol, unless the event is clearly attributable to the underlying disease or to an extraneous cause (including concomitant medications).
- Incidence of treatment-emergent adverse events (TEAEs) of REGN5837 in combination with odronextamab [From dose 1 of study treatment, until the date of progression, assessed up to study completion, approximatively 5 years]
Treatment-emergent adverse events (TEAEs) are defined as those AEs that newly occurred or worsened during the on-treatment period and any treatment-related serious adverse events (SAEs) that occurred during the post-treatment period.
- Severity of TEAEs of REGN5837 in combination with odronextamab [From dose 1 of study treatment, until the date of progression, assessed up to study completion, approximatively 5 years]
Treatment-emergent adverse events (TEAEs) are defined as those AEs that newly occurred or worsened during the on-treatment period and any treatment-related serious adverse events (SAEs) that occurred during the post-treatment period.
- Incidence of adverse events of special interest (AESIs) of REGN5837 in combination with odronextamab [From dose 1 of study treatment, until the date of progression, assessed up to study completion, approximatively 5 years]
An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate.
- Severity of AESIs of REGN5837 in combination with odronextamab [From dose 1 of study treatment, until the date of progression, assessed up to study completion, approximatively 5 years]
An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate.
Secondary Outcome Measures
- Concentrations of REGN5837 in the serum [Up to 90 days post last study drug administration]
- Concentrations of odronextamab in the serum [Up to 90 days post last study drug administration]
- Incidence of anti-drug antibodies (ADAs) to REGN5837 [Up to 90 days post last study drug administration]
- Incidence of ADAs to odronextamab [Up to 90 days post last study drug administration]
- Titer of ADAs to REGN5837 [Up to 90 days post last study drug administration]
- Titer of ADAs to odronextamab [Up to 90 days post last study drug administration]
- Overall response rate (ORR) according to the Lugano Classification of response [Through study completion, an average of approximately 5 years]
The ORR is defined as the proportion of patients who achieve a best overall response CR or PR during or following study treatment according to the Lugano Classification based on local investigator review.
- Complete response (CR) rate according to the Lugano Classification of response [Through study completion, an average of approximately 5 years]
The CR rate is defined as the proportion of patients who achieve a best overall response CR during or following study treatment according to the Lugano Classification based on local investigator review.
- Progression free survival (PFS) according to the Lugano Classification of response [Through study completion, an average of approximately 5 years]
PFS is defined as the time from the start of study treatment until the first date of progressive disease, or death due to any cause, whichever occurs first, based on local investigator review.
- Overall survival (OS) [Through study completion, an average of approximately 5 years]
OS is measured from the start of study treatment until death due to any cause.
- Duration of Response (DoR) according to the Lugano Classification of response [Through study completion, an average of approximately 5 years]
DOR is defined for responders (patients with a best overall response of CR or PR). It is the time from the date of the first documented CR or PR until the date of the first date of progressive disease, or death due to any cause, whichever occurs first, based on local investigator review.
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Have documented CD20+ aggressive B-NHL, with disease that has progressed after at least 2 lines of systemic therapy containing an anti-CD20 antibody and an alkylating agent.
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Measurable disease on cross sectional imaging as defined in the protocol
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Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
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Adequate bone marrow, renal and hepatic function as defined in the protocol
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During dose expansion phase of the study, participant should be willing to undergo mandatory tumor biopsies, if in the opinion of the investigator, the participants has an accessible lesion that can be biopsied without significant risk to the participant.
Key Exclusion Criteria:
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Prior treatments with allogeneic stem cell transplantation or solid organ transplantation, treatment with anti-CD20 x anti- CD3 bispecific antibody, such as odronextamab
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Diagnosis of mantle cell lymphoma (MCL)
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Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS lymphoma
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Treatment with any systemic anti-lymphoma therapy within 5 half-lives or within 14 days prior to first administration of study drug, whichever is shorter
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Standard radiotherapy within 14 days of first administration of study drug.
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Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone or corticosteroid equivalent within 72 hours of start of odronextamab
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Co-morbid conditions, as described in the protocol
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Infections, as described in the protocol
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Allergy/hypersensitivity: Known hypersensitivity to both allopurinol and rasburicase
NOTE: Other protocol defined inclusion / exclusion criteria apply
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Trial Management, Regeneron Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R5837-ONC-2019
- 2020-005084-32