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

Phase 3

Active, not recruiting

• Conditions: Diffuse Large B-cell Lymphoma (DLBCL)
• Interventions: Drug: Rituximab; Drug: Odronextamab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone/Prednisolone

• Registration Number: NCT06091865
• Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-10-13
• Study First Submitted QC: 2023-10-13
• Study First Posted: 2023-10-19
• Study Start: 2023-12-13
• Status Verified: 2025-04
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-15
• Primary Completion: 2028-03-30
• Study Completion: 2029-04-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 904

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 follicular 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Odronextamab + CHOP	Doxorubicin	Part 1, includes dose escalation (Part 1A), and randomized exploration of 2 regimens of odronextamab -cyclophosphamide, doxorubicin, vincristine, prednisone (Odro-CHOP) dose optimization (Part 1B).
Odronextamab + CHOP	Vincristine	Part 1, includes dose escalation (Part 1A), and randomized exploration of 2 regimens of odronextamab -cyclophosphamide, doxorubicin, vincristine, prednisone (Odro-CHOP) dose optimization (Part 1B).
Odronextamab + CHOP	Prednisone/Prednisolone	Part 1, includes dose escalation (Part 1A), and randomized exploration of 2 regimens of odronextamab -cyclophosphamide, doxorubicin, vincristine, prednisone (Odro-CHOP) dose optimization (Part 1B).
Rituximab + CHOP	Prednisone/Prednisolone	Part 2 is the randomized controlled portion, participants will receive either Odro-CHOP or R-CHOP.
Odronextamab + CHOP	Cyclophosphamide	Part 1, includes dose escalation (Part 1A), and randomized exploration of 2 regimens of odronextamab -cyclophosphamide, doxorubicin, vincristine, prednisone (Odro-CHOP) dose optimization (Part 1B).
Rituximab + CHOP	Rituximab	Part 2 is the randomized controlled portion, participants will receive either Odro-CHOP or R-CHOP.
Rituximab + CHOP	Cyclophosphamide	Part 2 is the randomized controlled portion, participants will receive either Odro-CHOP or R-CHOP.
Rituximab + CHOP	Doxorubicin	Part 2 is the randomized controlled portion, participants will receive either Odro-CHOP or R-CHOP.
Rituximab + CHOP	Vincristine	Part 2 is the randomized controlled portion, participants will receive either Odro-CHOP or R-CHOP.
Odronextamab + CHOP	Odronextamab	Part 1, includes dose escalation (Part 1A), and randomized exploration of 2 regimens of odronextamab -cyclophosphamide, doxorubicin, vincristine, prednisone (Odro-CHOP) dose optimization (Part 1B).

Primary Outcome Measures

Name	Time	Method
Incidence of dose limiting toxicities (DLTs)	Up to 35 days	Part 1A
Incidence of treatment emergent adverse events (TEAEs)	Up to 2 years	Part 1
Severity of TEAEs	Up to 2 years	Part 1
Progression free survival (PFS), assessed by independent central review (ICR)	Up to 5 years	Part 2

Secondary Outcome Measures

Name	Time	Method
Event-free survival (EFS) assessed by ICR	Up to 5 years	Part 2
Overall survival (OS)	Up to 5 years	Part 2
Best Overall response (BOR) as assessed by local investigators	Up to 22 weeks	Part 1 and Part 2
CR as assessed by local investigators	Up to 22 weeks	Part 1 and Part 2
Duration of response (DOR) as assessed by local investigators	Up to 5 years	Part 1 and Part 2
Odronextamab concentrations in serum when administered with CHOP	Up to 22 weeks	Part 1 and Part 2
Incidence of anti-drug antibodies (ADA) to odronextamab over the study duration	Up to 22 weeks	Part 1 and Part 2
Titer of ADA to odronextamab over the study duration	Up to 22 weeks	Part 1 and Part 2
Incidence of neutralizing antibodies (NAb) to odronextamab over the study duration	Up to 22 weeks	Part 1 and Part 2
PFS assessed by local investigator review	Up to 5 years	Part 2
EFS assessed by local investigator review	Up to 5 years	Part 2
BOR assessed by ICR	Up to 22 weeks	Part 2
DOR assessed by ICR	Up to 5 years	Part 2
Incidence of TEAEs	Up to 2 years	Part 2
Severity of TEAEs	Up to 2 years	Part 2
Measurable Residual Disease (MRD) status	Up to 22 weeks	Part 2
Duration of MRD-negativity	Up to 5 years	Part 2
Change in physical functioning as measured by European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C) 30	Up to 5 years	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.
Change in patient reported outcomes, as measured by EORTC QLQ-C30	Up to 5 years	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.
Change in patient reported outcomes, as measured by Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS)	Up to 5 years	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.
Change in patient reported outcomes, as measured by Patient Global Impression of Severity (PGIS)	Up to 5 years	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).
Change in patient reported outcomes, as measured by Patient Global Impression of Change (PGIC)	Up to 5 years	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.
Change in patient reported outcomes, as measured by EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L)	Up to 5 years	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".
Change in score of the Functional Assessment of Cancer Therapy-General (FACT-G ) GP5 item	Up to 5 years	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).
Complete response (CR) assessed by ICR	Up to 22 weeks	Part 2

Trial Locations

Locations (149)

Centrum Innowacyjnych Terapii Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie; 🇵🇱 Lublin, Poland

David Geffen School of Medicine at UCLA; 🇺🇸 Los Angeles, California, United States

University of California Irvine Medical Center; 🇺🇸 Orange, California, United States

University of California (UC) Davis; 🇺🇸 Sacramento, California, United States

Indiana University Melvin and Bren Simon Comprehensive Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

St Vincent Ascension at Peyton Manning Childrens Hospital; 🇺🇸 Indianapolis, Indiana, United States

Investigative Clinical Research of Indiana; 🇺🇸 Noblesville, Indiana, United States

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

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