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A Study to Learn How Well Odronextamab Combined With Chemotherapy Works and How Safe it is Compared to Rituximab and Chemotherapy in Adult Participants With Previously Untreated Follicular Lymphoma (OLYMPIA-2)

Primary Purpose

Follicular Lymphoma (FL)

Status

Recruiting

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Odronextamab

Rituximab

Cyclophosphamide

Doxorubicin

Vincristine

Prednisone/Prenisolone

About this trial

This is an interventional treatment trial for Follicular Lymphoma (FL) focused on measuring Non-Hodgkin lymphomas (NHL), Relapsed or Refractory (R/R) FL, B-cells NHL (B-NHL), Untreated FL, Odronextamab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria: Have diagnosis of cluster of differentiation 20 positive (CD20+) FL grade 1-3a, stage II bulky or stage III / IV For Part 1A: previously untreated participants who have Follicular Lymphoma International Prognostic Index (FLIPI)-1 score of 3 to 5, or R/R FL who have not received R-CHOP or R-CVP. For Part 1B: previously untreated participants who have FLIPI-1 score of 3 to 5 For Part 2: previously untreated participants who have FLIPI-1 score of 0 to 5 Have measurable disease on cross sectional imaging documented by diagnostic computed tomography [CT], or magnetic resonance imaging [MRI] imaging, as described in the protocol Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Adequate bone marrow and hepatic function. Key Exclusion Criteria: Participants with central nervous system lymphoma or leptomeningeal lymphoma Participants with histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma Participants with Waldenström macroglobulinemia (WM, lymphoplasmacytic lymphoma), grade 3b follicular lymphoma, chronic lymphocytic leukemia or small lymphocytic lymphoma Recent major surgery and history or organ transplantation A malignancy other than NHL unless the participant is adequately and definitively treated and 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. Note: Other protocol-defined Inclusion/Exclusion criteria apply

Sites / Locations

Investigative Clinical Research of IndianaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Odronextamab + Chemotherapy

Rituximab + Chemotherapy

Odronextamab + Chemotherapy + Maintenance

Odronextamab + Chemotherapy + No maintenance

Arm Description

Part 1 of the study includes ordonextamab dose escalation for participants with previously untreated FL and relapsed/refractory FL (Part 1A only) followed by a randomized exploration of 2 regimens of odronextamab (O) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with the objective of dose optimization (Part 1B) in previously untreated patients with FL.

In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.

In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy [CHOP, or cyclophosphamide, vincristine, and prednisone (CVP)], followed by odronextamab monotherapy maintenance.

In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy (CHOP, or CVP) without maintenance.

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicities (DLTs) for odronextamab in combination with chemotherapy

Part 1, DLT period

Incidence of treatment-emergent adverse events (TEAEs) of odronextamab in combination with chemotherapy

Part 1, Treatment period

Severity of TEAEs of odronextamab in combination with chemotherapy

Part 1, Treatment period

Complete Response rate at 30 months (CR30) assessed by independent central review (ICR)

Part 2

Secondary Outcome Measures

Odronextamab concentrations in serum when administered with chemotherapy

Part 1, Maintenance period and Part 2, Induction period

Odronextamab concentrations in serum when administered as monotherapy

Part 1 and Part 2, Maintenance period

Incidence of anti-odronextamab antibodies (ADAs)

Part 1 and Part 2

Titers of ADAs to odronextamab

Part 1 and Part 2

Incidence of neutralizing antibodies (NAb) to odronextamab

Part 1 and Part 2

Best overall response (BOR) as assessed by the investigator

Part 1, end of Induction period and end of Maintenance period

Progression free survival (PFS) as assessed by ICR

Part 2

CR30 as assessed by local investigator

Part 2

Change from baseline in patient reported physical functioning scale scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Cancer-30 (EORTC-QLQ-C30)

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 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.

PFS as assessed by local investigator

Part 2

Event-free survival (EFS) as assessed by ICR

Part 2

EFS as assessed by local investigator

Part 2

Overall Survival (OS)

Part 2

BOR as assessed by local investigator

Part 2

BOR as assessed by ICR

Part 2

Duration of response (DOR) assessed by ICR

Part 2

DOR as assessed by local investigator

Part 2

Time to next anti-lymphoma treatment (TTNT)

Part 2

Incidence of TEAEs

Part 2

Severity of TEAEs

Part 2

Change from baseline of patient reported health related quality of life (HRQoL) as measured by EORTC-QLQ-C30

Change from baseline in cancer disease as measured by EORTC-QLQ-C30

Change from baseline in treatment related symptoms as measured by EORTC-QLQ-C30

Change from baseline in patient-reported lymphoma disease as measured by the Lymphoma Subscale of the Functional Assessment of Cancer Treatment-Lymphoma (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.

Change from baseline in treatment-related symptoms as measured by the Lymphoma Subscale of the Functional Assessment of Cancer Treatment-Lymphoma (FACT-LymS)

Change from baseline in patient-reported general health status per EuroQol-5 Dimensions-5 Levels (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".

Change from baseline in patient-reported treatment side effects burden per FACT-Lym General Population 5 (GP5) Item Score

Part 2 A single item Global Population item 5 (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).

Change from baseline in 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).

Change from baseline in 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.

Change in score of the FACT-G GP5 item in the patient population

Full Information

NCT ID

NCT06097364

First Posted

October 18, 2023

Last Updated

October 18, 2023

Sponsor

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT06097364

Brief Title

A Study to Learn How Well Odronextamab Combined With Chemotherapy Works and How Safe it is Compared to Rituximab and Chemotherapy in Adult Participants With Previously Untreated Follicular Lymphoma

Acronym

OLYMPIA-2

Official Title

A Phase 3, Open-Label, Randomized Study to Compare the Efficacy and Safety of Odronextamab (REGN1979), an Anti-CD20x Anti-CD3 Bispecific Antibody, Combined With Chemotherapy Versus Rituximab Combined With Chemotherapy in Previously Untreated Participants With Follicular Lymphoma (OLYMPIA-2)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 8, 2023 (Anticipated)

Primary Completion Date

January 10, 2030 (Anticipated)

Study Completion Date

January 10, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study is researching an experimental drug called odronextamab, referred to as study drug. The study is focused on participants with previously untreated follicular lymphoma in Part 2, as well as participants with lymphoma that has come back after treatment (called "relapsed") or did not respond to treatment (called "refractory"), in Part 1. Follicular lymphoma is a type of non-Hodgkin lymphoma or NHL. This study is made up of 3 parts: Part 1A (non-randomized), Part 1B and Part 2 (randomized - controlled). 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 to be used in Part 2 of the study. The aim of Part 2 of the study is to assess how effective the combination of the study drug with chemotherapy is in comparison with the combination of rituximab and chemotherapy (the current standard-of-care for NHL). 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 How much study drug is in your 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 your quality-of-life and ability to complete routine daily activities

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Follicular Lymphoma (FL)

Keywords

Non-Hodgkin lymphomas (NHL), Relapsed or Refractory (R/R) FL, B-cells NHL (B-NHL), Untreated FL, Odronextamab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

733 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Odronextamab + Chemotherapy

Arm Type

Experimental

Arm Description

Arm Title

Rituximab + Chemotherapy

Arm Type

Active Comparator

Arm Description

In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.

Arm Title

Odronextamab + Chemotherapy + Maintenance

Arm Type

Experimental

Arm Description

Arm Title

Odronextamab + Chemotherapy + No maintenance

Arm Type

Experimental

Arm Description

In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy (CHOP, or CVP) without maintenance.

Intervention Type

Drug

Intervention Name(s)

Odronextamab

Other Intervention Name(s)

REGN1979

Intervention Description

Administered by intravenous (IV) infusion

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

Rituxan

Intervention Description

Administered by IV infusion, or subcutaneous (SC)

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cytoxan

Intervention Description

Administered by IV infusion

Intervention Type

Drug

Intervention Name(s)

Doxorubicin

Other Intervention Name(s)

Adriamycin

Intervention Description

Administered by IV infusion

Intervention Type

Drug

Intervention Name(s)

Vincristine

Other Intervention Name(s)

Oncovin

Intervention Description

Administered by IV infusion

Intervention Type

Drug

Intervention Name(s)

Prednisone/Prenisolone

Other Intervention Name(s)

Deltasone/Omnipred

Intervention Description

Administered orally (PO)

Primary Outcome Measure Information:

Title

Incidence of dose limiting toxicities (DLTs) for odronextamab in combination with chemotherapy

Description

Part 1, DLT period

Time Frame

Up to 35 days

Title

Incidence of treatment-emergent adverse events (TEAEs) of odronextamab in combination with chemotherapy

Description

Part 1, Treatment period

Time Frame

Up to 2 years

Title

Severity of TEAEs of odronextamab in combination with chemotherapy

Description

Part 1, Treatment period

Time Frame

Up to 2 years

Title

Complete Response rate at 30 months (CR30) assessed by independent central review (ICR)

Description

Part 2

Time Frame

Up to 30 months

Secondary Outcome Measure Information:

Title

Odronextamab concentrations in serum when administered with chemotherapy

Description

Part 1, Maintenance period and Part 2, Induction period

Time Frame

Up to 30 months

Title

Odronextamab concentrations in serum when administered as monotherapy

Description

Part 1 and Part 2, Maintenance period

Time Frame

Up to 30 months

Title

Incidence of anti-odronextamab antibodies (ADAs)

Description

Part 1 and Part 2

Time Frame

Up to 30 months

Title

Titers of ADAs to odronextamab

Description

Part 1 and Part 2

Time Frame

Up to 30 months

Title

Incidence of neutralizing antibodies (NAb) to odronextamab

Description

Part 1 and Part 2

Time Frame

Up to 30 months

Title

Best overall response (BOR) as assessed by the investigator

Description

Part 1, end of Induction period and end of Maintenance period

Time Frame

Up to 30 months

Title

Progression free survival (PFS) as assessed by ICR

Description

Part 2

Time Frame

Up to 5 years

Title

CR30 as assessed by local investigator

Description

Part 2

Time Frame

Up to 30 months

Title

Change from baseline in patient reported physical functioning scale scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Cancer-30 (EORTC-QLQ-C30)

Description

Time Frame

Up to 5 years

Title

PFS as assessed by local investigator

Description

Part 2

Time Frame

Up to 5 years

Title

Event-free survival (EFS) as assessed by ICR

Description

Part 2

Time Frame

Up to 5 years

Title

EFS as assessed by local investigator

Description

Part 2

Time Frame

Up to 5 years

Title

Overall Survival (OS)

Description

Part 2

Time Frame

Up to 5 years

Title

BOR as assessed by local investigator

Description

Part 2

Time Frame

Up to 30 months

Title

BOR as assessed by ICR

Description

Part 2

Time Frame

Up to 30 months

Title

Duration of response (DOR) assessed by ICR

Description

Part 2

Time Frame

Up to 5 years

Title

DOR as assessed by local investigator

Description

Part 2

Time Frame

Up to 5 years

Title

Time to next anti-lymphoma treatment (TTNT)

Description

Part 2

Time Frame

Up to 5 years

Title

Incidence of TEAEs

Description

Part 2

Time Frame

Up to 2 years

Title

Severity of TEAEs

Description

Part 2

Time Frame

Up to 2 years

Title

Change from baseline of patient reported health related quality of life (HRQoL) as measured by EORTC-QLQ-C30

Description

Time Frame

Up to 5 years

Title

Change from baseline in cancer disease as measured by EORTC-QLQ-C30

Description

Time Frame

Up to 5 years

Title

Change from baseline in treatment related symptoms as measured by EORTC-QLQ-C30

Description

Time Frame

Up to 5 years

Title

Change from baseline in patient-reported lymphoma disease as measured by the Lymphoma Subscale of the Functional Assessment of Cancer Treatment-Lymphoma (FACT-LymS)

Description

Time Frame

Up to 5 years

Title

Change from baseline in treatment-related symptoms as measured by the Lymphoma Subscale of the Functional Assessment of Cancer Treatment-Lymphoma (FACT-LymS)

Description

Time Frame

Up to 5 years

Title

Change from baseline in patient-reported general health status per EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)

Description

Time Frame

Up to 5 years

Title

Change from baseline in patient-reported treatment side effects burden per FACT-Lym General Population 5 (GP5) Item Score

Description

Time Frame

Up to 5 years

Title

Change from baseline in Patient Global Impression of Severity (PGIS)

Description

Time Frame

Up to 5 years

Title

Change from baseline in Patient Global Impression of Change (PGIC)

Description

Time Frame

Up to 5 years

Title

Change in score of the FACT-G GP5 item in the patient population

Description

Time Frame

Up to 5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Clinical Trials Administrator

Phone

844-734-6643

clinicaltrials@regeneron.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trial Management

Organizational Affiliation

Regeneron Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Investigative Clinical Research of Indiana

City

Noblesville

State/Province

Indiana

ZIP/Postal Code

46062

Country

United States

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

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 made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.

IPD Sharing Access Criteria

Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

IPD Sharing URL

https://vivli.org/

Learn more about this trial

A Study to Learn How Well Odronextamab Combined With Chemotherapy Works and How Safe it is Compared to Rituximab and Chemotherapy in Adult Participants With Previously Untreated Follicular Lymphoma

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