A Trial to Learn How Effective and Safe Odronextamab is Compared to Standard of Care for Adult Participants With Previously Treated Aggressive B-cell Non-Hodgkin Lymphoma

Phase 3RecruitingNCT06230224

Regeneron Pharmaceuticals216 enrolled

Overview

This study is researching an experimental drug called odronextamab, referred to as study drug. The study is focused on patients with previously treated aggressive B-cell non-Hodgkin lymphoma whose cancer has stopped responding to treatment (also known as 'refractory') or has returned (also known as 'relapsed'). The aim of the study is to see how safe, tolerable and effective the study drug is when given alone. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug versus Standard of Care (SOC) * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects) * Comparing the impact from the study drug versus SOC on quality-of-life and ability to complete routine daily activities

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

216

Conditions

B-Cell Non-Hodgkin Lymphoma (B-NHL)

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Histologically proven aggressive B-NHL, as described in the protocol. Availability of tumor tissue for submission to central laboratory is required for study enrollment. Archival tumor tissue for histological assessment prior to enrollment is allowed 2. Have primary refractory or relapse 12 months or less (≤) from initiation of frontline therapy Only patients who received 1 prior line of therapy containing an anti-Cluster of Differentiation 20 (CD20) antibody and anthracycline are allowed for enrollment 3. Have measurable disease with at least one nodal lesion with longer diameter (LDi) greater than 1.5 cm or at least one extranodal lesion with LDi greater than 1.0 cm, documented by diagnostic imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) 4. Intent to proceed to autologous stem cell transplant (ASCT), as described in the protocol 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 6. Adequate hematologic and organ function. Key Exclusion Criteria: 1. Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL, as described in the protocol 2. History of or current relevant CNS pathology, as described in the protocol 3. A malignancy other than NHL unless the participant is adequately and definitively treated and is cancer free for at least 3 years, with the exception of localized prostate cancer, cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that was definitively treated 4. Any other significant active disease or medical condition that could interfere with the conduct of the study or put the participant at significant risk, as described in the protocol 5. Wash-out period from prior anti-lymphoma treatments and infections, as described in the protocol 6. Allergy/hypersensitivity to study drug, or excipients. NOTE: Other protocol defined inclusion / exclusion criteria apply

Outcomes

Primary Outcomes

Event-free survival (EFS) as assessed by independent central review (ICR)

Time frame: Assessed up to 3 years

Secondary Outcomes

Progression free survival (PFS) as assessed by ICR

Time frame: Assessed up to 3 years

Best overall response (BOR) as assessed by ICR

Time frame: Assessed up to 6 months

Overall survival (OS)

Time frame: Assessed up to 3 years

Overall change in physical functioning as measured by scores of the physical function scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30)

The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a global health status (GHS)/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties). For the functioning scales and global health status / QoL, scores range from 1 = "very poor" to 7 = "excellent" with higher scores indicate better functioning; for the symptom scales, scores range from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden.

Time frame: Assessed up to 3 years

EFS as assessed by local investigator

Time frame: Assessed up to 3 years

PFS as assessed by local investigator

Time frame: Assessed up to 3 years

BOR as assessed by local investigator

Time frame: Assessed up to 6 months

Complete response (CR) as assessed by ICR

Time frame: Assessed up to 6 months

CR as assessed by local investigator

Time frame: Assessed up to 6 months

Duration of response (DOR) assessed by ICR

Time frame: Assessed up to 3 years

DOR assessed by local investigator

Time frame: Assessed up to 3 years

Incidence of treatment-emergent adverse events (TEAEs)

Time frame: Assessed up to 1 year

Severity of TEAEs

Time frame: Assessed up to 1 year

Odronextamab concentrations in serum

Time frame: Assessed up to 6 months

Incidence of anti-drug antibodies (ADAs) to odronextamab over the study duration

Time frame: Assessed up to 6 months

Titers of ADAs to odronextamab over the study duration

Time frame: Assessed up to 6 months

Incidence of neutralizing antibodies (NAb) to odronextamab over the study duration

Time frame: Assessed up to 6 months

Measurable residual disease (MRD) status

Time frame: Assessed up to 6 months

Overall change in patient-reported outcomes (PROs), as measured by scores of the EORTCQLQ- C30

The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties). For the functioning scales and global health status / QoL, scores range from 1 = "very poor" to 7 = "excellent" with higher scores indicate better functioning; for the symptom scales, scores range from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden.

Time frame: Assessed up to 3 years

Overall change in PROs, as measured by scores of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-LymS)

The FACT-Lym lymphoma subscale (LymS) includes 15 items to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). Higher scores are associated with a worse quality of life.

Time frame: Assessed up to 3 years

Overall change in PROs, as measured by scores of the EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L)

The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: "no problems", "slight problems", "moderate problems", "severe problems" and "extreme problems". The EQ VAS records the participant's self-rated health on a vertical visual analogue scale where the endpoints are labeled "Best imaginable health state" and "Worst imaginable health state".

Time frame: Assessed up to 3 years

Overall change in score of the Global Population item 5 (GP5) of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire

A single item GP5 of the validated FACT-G questionnaire will be used to assess from the participant perspective the overall impact of treatment side-effect. The question item is on a 5-point scale ranging from "not at all" (0) to "very much" (4).

Time frame: Assessed up to 3 years

A Trial to Learn How Effective and Safe Odronextamab is Compared to Standard of Care for Adult Participants With Previously Treated Aggressive B-cell Non-Hodgkin Lymphoma

Overview

Conditions

Interventions

Eligibility

Locations (99)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts