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

Follicular Lymphoma (FL) Clinical Trial

— 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06097364
• Other study ID #: R1979-ONC-2075
• Secondary ID: 2022-502113-28-0
• Status: Recruiting
• Phase: Phase 3
• Start date: November 14, 2023
• Est. completion date: January 24, 2030

Study information

• Verified date: September 2023
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 733
• Est. completion date: January 24, 2030
• Est. primary completion date: January 24, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Have diagnosis of cluster of differentiation 20 positive (CD20+) FL grade 1-3a, stage II bulky or stage III / IV

1. 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.

2. For Part 1B: previously untreated participants who have FLIPI-1 score of 3 to 5

3. For Part 2: previously untreated participants who have FLIPI-1 score of 0 to 5

2. Have measurable disease on cross sectional imaging documented by diagnostic computed tomography [CT], or magnetic resonance imaging [MRI] imaging, as described in the protocol

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

4. Adequate bone marrow and hepatic function.

Key Exclusion Criteria:

1. Participants with central nervous system lymphoma or leptomeningeal lymphoma

2. Participants with histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma

3. Participants with Waldenström macroglobulinemia (WM, lymphoplasmacytic lymphoma), grade 3b follicular lymphoma, chronic lymphocytic leukemia or small lymphocytic lymphoma

4. Recent major surgery and history or organ transplantation

5. 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

Related Conditions & MeSH terms

• Follicular Lymphoma (FL)
• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• Odronextamab
Administered by intravenous (IV) infusion
• Rituximab
Administered by IV infusion, or subcutaneous (SC)
• Cyclophosphamide
Administered by IV infusion
• Doxorubicin
Administered by IV infusion
• Vincristine
Administered by IV infusion
• Prednisone/Prenisolone
Administered orally (PO)

Locations

Country	Name	City	State
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Belgium	Hopital Universitaire de Bruxelles - Site Bordet	Brussels
Belgium	University Hospital Ghent	Ghent	East Flanders
Belgium	AZ Groeninge	Kortrijk	West Flanders
Belgium	Vzw - Vitaz	Sint-Niklaas	East Flanders
Belgium	CHR Verviers	Verviers	Liege
Chile	Clinica Universidad de los Andes	Santiago
Chile	Immunocel	Santiago	Santiago Metropolitan Region
Chile	Pontificia Universidad Catolica de Chile	Santiago	Region Metropolitana
Italy	Instituto Scientifico Romagnolo	Meldola	Forli-Cesena
Italy	Universita degli Studi di Napoli Federico II	Naples	Campania
Italy	Azienda Unita Sanitaria Locale	Ravenna	Emilia-Romagna
Poland	Pratia Onkologia Katowice	Katowice	Silesia
Spain	Clinica Universidad de Navarra - Sede Madrid	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Hospital Universitario Quironsalud Madrid	Madrid
Spain	Hosptial Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturas
Spain	Clinica Universidad de Navarra - Sede Pamplona	Pamplona	Navarre
Spain	Consorci Corporacio Sanitaria Parc Tauli	Sabadell	Barcelona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitari Mutua Terrassa	Terrassa
Spain	Hospital Universitario de Toledo	Toledo
Spain	Instituto Valenciano de Oncologia	Valencia
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	Taipei Municipal Wan Fang Hospital	Taipei
Thailand	Chulalongkorn University	Bangkok
Thailand	Srinagrind Hopsital	Khon Kaen
Turkey	Sakayra University Training and Research Hospital	Adapazari	Sakarya
Turkey	Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital	Ankara
Turkey	Gazi University	Ankara
Turkey	Istanbul University	Istanbul
Turkey	VKV American Hospital	Istanbul
Turkey	Erciyes University	Kayseri
Turkey	Tekirdag Namik Kemal University Hospital	Tekirdag
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Aberdeenshire
United Kingdom	Royal Cornwall Hospital NHS Trust	Truro	Cornwall
United States	Henry Ford Hospital	Detroit	Michigan
United States	Cancer and Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	Center for Oncology and Blood Disorders	Houston	Texas
United States	University of Kentucky	Lexington	Kentucky
United States	Investigative Clinical Research of Indiana	Noblesville	Indiana
United States	Community Cancer Trials of Utah	Ogden	Utah
United States	ProHealth Care Inc	Waukesha	Wisconsin
United States	Clinical Research Alliance, Inc.	Westbury	New York

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Chile,  Italy,  Poland,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicities (DLTs) for odronextamab in combination with chemotherapy	Part 1, DLT period	Up to 35 days
Primary	Incidence of treatment-emergent adverse events (TEAEs) of odronextamab in combination with chemotherapy	Part 1, Treatment period	Up to 2 years
Primary	Severity of TEAEs of odronextamab in combination with chemotherapy	Part 1, Treatment period	Up to 2 years
Primary	Complete Response rate at 30 months (CR30) assessed by independent central review (ICR)	Part 2	Up to 30 months
Secondary	Odronextamab concentrations in serum when administered with chemotherapy	Part 1, Maintenance period and Part 2, Induction period	Up to 30 months
Secondary	Odronextamab concentrations in serum when administered as monotherapy	Part 1 and Part 2, Maintenance period	Up to 30 months
Secondary	Incidence of anti-odronextamab antibodies (ADAs)	Part 1 and Part 2	Up to 30 months
Secondary	Titers of ADAs to odronextamab	Part 1 and Part 2	Up to 30 months
Secondary	Incidence of neutralizing antibodies (NAb) to odronextamab	Part 1 and Part 2	Up to 30 months
Secondary	Best overall response (BOR) as assessed by the investigator	Part 1, end of Induction period and end of Maintenance period	Up to 30 months
Secondary	Progression free survival (PFS) as assessed by ICR	Part 2	Up to 5 years
Secondary	CR30 as assessed by local investigator	Part 2	Up to 30 months
Secondary	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.	Up to 5 years
Secondary	PFS as assessed by local investigator	Part 2	Up to 5 years
Secondary	Event-free survival (EFS) as assessed by ICR	Part 2	Up to 5 years
Secondary	EFS as assessed by local investigator	Part 2	Up to 5 years
Secondary	Overall Survival (OS)	Part 2	Up to 5 years
Secondary	BOR as assessed by local investigator	Part 2	Up to 30 months
Secondary	BOR as assessed by ICR	Part 2	Up to 30 months
Secondary	Duration of response (DOR) assessed by ICR	Part 2	Up to 5 years
Secondary	DOR as assessed by local investigator	Part 2	Up to 5 years
Secondary	Time to next anti-lymphoma treatment (TTNT)	Part 2	Up to 5 years
Secondary	Incidence of TEAEs	Part 2	Up to 2 years
Secondary	Severity of TEAEs	Part 2	Up to 2 years
Secondary	Change from baseline of patient reported health related quality of life (HRQoL) as measured by 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.	Up to 5 years
Secondary	Change from baseline in cancer disease as measured by 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.	Up to 5 years
Secondary	Change from baseline in treatment related symptoms as measured by 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.	Up to 5 years
Secondary	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.	Up to 5 years
Secondary	Change from baseline in treatment-related symptoms 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.	Up to 5 years
Secondary	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".	Up to 5 years
Secondary	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).	Up to 5 years
Secondary	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).	Up to 5 years
Secondary	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.	Up to 5 years
Secondary	Change in score of the FACT-G GP5 item in the patient population	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).	Up to 5 years