A Study to Compare How Well Odronextamab Combined With Chemotherapy Works and How Safe it is Against Rituximab Combined With Chemotherapy, in Adult Patients With Previously Untreated Diffuse Large B-cell Lymphoma

Phase 3RecruitingNCT06091865

Regeneron Pharmaceuticals904 enrolled

Overview

This study is researching an experimental drug called odronextamab, referred to as study drug, when used in combination with chemotherapy. The study is focused on patients with Diffuse Large B-cell Lymphoma (DLBCL) that have not been treated before (called "previously untreated"). Patients with DLBCL that have come back after treatment (called "relapsed"), or have not responded to treatment (called "refractory"), can also participate in this study. This study will be made up of Part 1A, Part 1B, and Part 2.The aim of Part 1A and Part 1B of the study is to see how safe and tolerable the study drug in combination with chemotherapy is and to determine the dose and schedule of the study drug to be combined with chemotherapy in Part 2 of the study. The aim of Part 2 of the study is to see how effective the combination of the study drug with chemotherapy is in comparison with the combination of rituximab (the comparator drug), and chemotherapy, the current standard of care treatment approved for DLBCL. Standard of care means the usual medication expected and used when receiving treatment for a condition. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug when combined with chemotherapy * 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) * The impact from the study drug on quality of life and ability to complete routine daily activities

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

904

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Previously untreated participants for lymphoma with documented Cluster of Differentiation 20+ (CD20+) DLBCL, as described in the protocol OR relapsed or refractory DLBCL, for whom next available standard of care therapy is not available or deemed ineligible according to the investigator (Part 1A only) 2. Measurable disease with at least one nodal lesion or at least one extranodal lesion, as described in the protocol 3. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 4. Life expectancy ≥ 12 months 5. International Prognostic Index (IPI) of 3 to 5 (part 1 only) and ≥2 (part 2) for untreated DLBCL only 6. Adequate hematologic and organ function, as defined in the protocol. Key Exclusion Criteria: 1. Primary Central Nervous System (CNS) lymphoma or known involvement by non-primary CNS NHL and history or current relevant CNS pathology 2. Another active malignancy, significant active disease or medical condition, as described in the protocol 3. Peripheral neuropathy Grade ≥3 4. Treatment with any systemic anti-lymphoma therapy, except for participants with Relapsed/Refractory (R/R) DLBCL and participants with DLBCL transformed from an indolent lymphoma after treatment with systemic anti-lymphoma therapy. 5. Any other therapy or investigational treatment within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the start of study treatment 6. Recent major surgery, prior organ transplantation, or standard radiotherapy, as described in the protocol 7. Allergy/hypersensitivity to study drugs, as described in the protocol 8. Infections such as any active infection (bacterial, viral, fungal, mycobacterial, parasitic or other), active Coronavirus Disease (COVID-19) infection, uncontrolled infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV), Cytomegalovirus (CMV) infection, as described in the protocol. Note: Other protocol-defined Inclusion/ Exclusion criteria apply

Outcomes

Primary Outcomes

Incidence of Dose Limiting Toxicities (DLTs)

Part 1A

Time frame: Up to 35 days

Incidence of Treatment Emergent Adverse Events (TEAEs)

Part 1

Time frame: Up to 2 years

Severity of TEAEs

Part 1

Time frame: Up to 2 years

Progression Free Survival (PFS), assessed by Independent Central Review (ICR)

Part 2

Time frame: Up to 5 years

Secondary Outcomes

Event-Free Survival (EFS) assessed by ICR

Part 2

Time frame: Up to 5 years

Complete Response (CR) assessed by ICR

Part 2

Time frame: Up to 22 weeks

Overall Survival (OS)

Part 2

Time frame: Up to 5 years

Best Overall Response (BOR) as assessed by local investigators

Part 1 and Part 2

Time frame: Up to 22 weeks

CR as assessed by local investigators

Part 1 and Part 2

Time frame: Up to 22 weeks

Duration of Response (DOR) as assessed by local investigators

Part 1 and Part 2

Time frame: Up to 5 years

Odronextamab concentrations in serum when administered with CHOP

Part 1 and Part 2

Time frame: Up to 22 weeks

Occurrence of Anti-Drug Antibodies (ADA) to odronextamab

Part 1 and Part 2

Time frame: Up to 22 weeks

Magnitude of ADA to odronextamab

Part 1 and Part 2

Time frame: Up to 22 weeks

PFS assessed by local investigator review

Part 2

Time frame: Up to 5 years

EFS assessed by local investigator review

Part 2

Time frame: Up to 5 years

BOR assessed by ICR

Part 2

Time frame: Up to 22 weeks

DOR assessed by ICR

Part 2

Time frame: Up to 5 years

Incidence of TEAEs

Part 2

Time frame: Up to 2 years

Severity of TEAEs

Part 2

Time frame: Up to 2 years

Minimal Residual Disease (MRD) status

Part 2

Time frame: Up to 22 weeks

Change in physical functioning as measured by European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C) 30

Part 2 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: Up to 5 years

Change in patient reported outcomes, as measured by EORTC QLQ-C30

Time frame: Up to 5 years

Change in patient reported outcomes, as measured by Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS)

Part 2 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: Up to 5 years

Change in patient reported outcomes, as measured by Patient Global Impression of Severity (PGIS)

Part 2 The PGIS includes a single-item to assess how a patient perceives the overall severity of cancer symptoms over the past 7 days. Patients will choose the response that best describes the severity of their overall cancer symptoms with options on a 5-point scale ranging from 1 (No symptoms) to 4 (Very Severe).

Time frame: Up to 5 years

Change in patient reported outcomes, as measured by Patient Global Impression of Change (PGIC)

Part 2 The PGIC item includes a single-item to assess how a patient perceives their overall change in health status since the start of study treatment. Patients will choose from response options on a 7-point scale ranging from 1 (Much Better) to 7 (Much worse); 1- Much Better, 2-Moderately Better, 3-A Little Better, 4-About the Same, 5-A Little Worse, 6-Moderately Worse, 7-Much Worse.

Time frame: Up to 5 years

Change in patient reported outcomes, as measured by EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L)

Part 2 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: Up to 5 years

Change in score of the Functional Assessment of Cancer Therapy-General (FACT-G ) GP5 item

Part 2 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: Up to 5 years

A Study to Compare How Well Odronextamab Combined With Chemotherapy Works and How Safe it is Against Rituximab Combined With Chemotherapy, in Adult Patients With Previously Untreated Diffuse Large B-cell Lymphoma

Overview

Conditions

Interventions

Eligibility

Locations (185)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts