A Trial to Learn if Odronextamab is Safe and Well-tolerated and How Well it Works Compared to Rituximab Combined With Different Types of Chemotherapy for Participants With Follicular Lymphoma

Follicular Lymphoma (FL) Clinical Trial

— OLYMPIA-1  

Official title:

A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Odronextamab (REGN1979), an Anti-CD20 X Anti-CD3 Bispecific Antibody Versus Investigator's Choice in Previously Untreated Participants With Follicular Lymphoma (OLYMPIA-1)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06091254
• Other study ID #: R1979-HM-2298
• Secondary ID: 2022-502660-20-0
• Status: Recruiting
• Phase: Phase 3
• Start date: December 12, 2023
• Est. completion date: April 3, 2029

Study information

• Verified date: December 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 (a type of non-Hodgkin lymphoma or NHL). This study will be made up of two parts: Part 1 (non-randomized) and Part 2 (randomized - controlled). The aim of Part 1 of the study is to see how safe and tolerable the study drug is. The aim of Part 2 of the study is to see how the study drug works compared to 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 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: 478
• Est. completion date: April 3, 2029
• Est. primary completion date: April 3, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Diagnosis of cluster of differentiation 20^+ (CD20^+) FL Grade 1-3a, stage II bulky or stage III / IV

2. Need for treatment as described in the protocol

3. Have measurable disease on cross-sectional imaging documented by diagnostic imaging Computed tomography (CT) or Magnetic resonance imaging (MRI)

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

5. Adequate bone marrow function and hepatic function

Key Exclusion Criteria:

1. Central nervous system (CNS) lymphoma or leptomeningeal lymphoma

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

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

4. Treatment with any systemic anti-lymphoma therapy

5. Infections and allergy/hypersensitivity to study drug or excipient NOTE: Other protocol defined inclusion / exclusion criteria apply

Related Conditions & MeSH terms

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

Intervention

Drug:
• Odronextamab
Administered by intravenous infusion (IV)
• Rituximab
Rituximab will be administered by IV, or subcutaneously (SC)
• Cyclophosphamide
Administered by IV as part of Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) chemotherapy, or Cyclophosphamide, Vincristine, Prednisone (CVP) chemotherapy
• Doxorubicin
Administered by IV as part of CHOP chemotherapy
• Vincristine
Administered by IV as part of CHOP, and CVP chemotherapy
• Prednisone/prednisolone
Administered orally (PO) as part of CVP chemotherapy
• Bendamustine
Administered by IV as part of chemotherapy (Rituximab-Bendamustine)

Locations

Country	Name	City	State
Australia	Icon Cancer Care, Wesley Clinic	Auchenflower	Queensland
Australia	Epworth Freemasons Hospital	East Melbourne	Victoria
Austria	Krankenhaus der Elisabethinen Linz GmbH	Linz
Chile	Inmunocel	Las Condes
Czechia	Fakultni Nemocnice Hradec Kralove	Hradec Kralove 5
Israel	Assuta Ashdod Medical Center	Ashdod
Israel	Bnai Zion Medical Center	Haifa
Israel	Sharett Institute Of Oncology, Hadassah Univ Hospital - Ein Karem, Hadassah Medical Organization	Jerusalem
Israel	Western Galilee Hospital	Nahariya
Israel	Rabin Medical Center	Petah Tikva
Israel	The Chaim Sheba Medical Center At Tel Hashomer, Sackler School Of Medicine, Tel Aviv University	Ramat-Gan
Israel	The Tel Aviv Sourasky Medical Center	Tel-Aviv
Italy	FPO-IRCCS Candiolo Cancer Institute	Candiolo
Italy	IRCCS - Azienda Ospedaliera Universitaria - IST San Martino	Genova
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS	Meldola
Italy	AOU maggiore della Carita'	Novara
Italy	Azienda Unita Sanitaria Locale di Ravenna - Ospedale S. Maria delle Croci di Ravenna	Ravenna
Poland	Pratia Onkologia Katowice	Katowice
Poland	Pratia MCM Krakow	Krakow	Malopolskie
Poland	Centrum Medyczne Pratia Poznan	Skorzewo
Spain	Complejo Hospitalario Universitario A Coruna	A Coruna
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital HM Sanchinarro	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Hospital Universitari Son Espases	Palma de Mallorca
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Hospital Universitario de Navarra	Pamplona
Spain	University Hospital Quironsalud Madrid	Pozuelo de Alarcon
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Marques De Valdecilla	Santander
Spain	Hospital Universitario Virgen de Valme	Sevilla
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Complejo Hospitalario de Toledo (CHT) Hospital Virgen de la Salud (HVS) Hospital Universitario de Toledo	Toledo
Spain	Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)	Valencia
Switzerland	Kantonsspital Baden AG (KSB)	Baden
Switzerland	University Hospital Basel	Basel
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	Kantonsspital Winterthur (KSW)	Winterthur
Taiwan	Kaohsiung Medical University-Kaohsiung Medical University	Kaohsiung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital	Taoyuan
Turkey	Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital	Ankara
Turkey	Gazi University Medical Faculty	Ankara
Turkey	American Hospital	Istanbul
Turkey	Istanbul University Capa Faculty of Medicine	Istanbul
Turkey	Erciyes University Medical Faculty	Kayseri
Turkey	Sakarya University Training and Research Hospital	Sakarya
Turkey	Namik Kemal Universitesi	Tekirdag
United Kingdom	Beatson West of Scotland Cancer Centre - Greater Glasgow Health Board	Glasgow
United Kingdom	Norfolk and Norwich University Hospital - Norfolk and Norwich University Hospitals NHS Foundation Trust	Norwich	Norfolk
United Kingdom	Derriford Hospital - University Hospitals Plymouth NHS Trust	Plymouth	Devon
United Kingdom	Royal Cornwall Hospital NHS Trust	Truro
United States	University of North Carolina Medical Center - UNC Hospitals Radiation Oncology Clinic	Chapel Hill	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Center for Oncology and Blood Disorders (COBD)	Houston	Texas
United States	Icahn School of Medicine at Mount Sinai (ISMMS) - The Mount Sinai Hospital (MSH)	New York	New York
United States	Investigative Clinical Research of Indiana, LLC	Noblesville	Indiana
United States	University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center	Orange	California
United States	Stony Brook University Hospital	Stony Brook	New York
United States	The University of Texas Health Science Center at Tyler D/B/A UT Health East Texas HOPE Cancer Center	Tyler	Texas
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,  Austria,  Chile,  Czechia,  Israel,  Italy,  Poland,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicities (DLTs) for odronextamab	Part 1	Up to 35 days
Primary	Incidence of treatment-emergent adverse events (TEAEs) of odronextamab	Part 1	Up to 2 years
Primary	Severity of TEAEs of odronextamab	Part 1	Up to 2 years
Primary	Complete Response at 30 months (CR30) as assessed by independent central review	Part 2	Up to 30 months
Secondary	Concentrations of odronextamab in serum	Part 1	Up to 30 months
Secondary	Incidence of anti-odronextamab antibodies (ADAs)	Part 1	Up to 30 months
Secondary	Titer of ADAs	Part 1	Up to 30 months
Secondary	Incidence of neutralizing antibodies (NAbs) to odronextamab	Part 1	Up to 30 months
Secondary	Objective response as assessed by the investigator	Part 1	Up to 30 months
Secondary	Progression-free survival (PFS) as assessed by independent central review	Part 2	Up to 5 years
Secondary	Event-free survival (EFS) as assessed by independent central review	Part 2	Up to 5 years
Secondary	CR30 as assessed by local investigator	Part 2	Up to 30 months
Secondary	Overall mean change from baseline in physical function [European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 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	Overall survival (OS)	Part 2	Up to 5 years
Secondary	PFS as assessed by the local investigator	Part 2	Up to 5 years
Secondary	EFS as assessed by the local investigator	Part 2	Up to 5 years
Secondary	Objective response assessed by local investigator	Part 2	Up to 30 months
Secondary	Objective response assessed by independent central review	Part 2	Up to 30 months
Secondary	Duration of response (DOR) assessed by independent central review	Part 2	Up to 5 years
Secondary	DOR 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	Odronextamab concentrations in serum during the induction period	Part 2	Up to 30 months
Secondary	Odronextamab concentrations in serum during the maintenance period	Part 2	Up to 30 months
Secondary	Incidence of ADAs to odronextamab over time	Part 2	Up to 30 months
Secondary	Titer of ADAs to odronextamab over time	Part 2	Up to 30 months
Secondary	Incidence of NAbs to odronextamab over time	Part 2	Up to 30 months
Secondary	Overall mean changes in scores of patient reported outcomes (PROs), as measured by the validated instruments EORTCQLQ- 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	Overall mean changes in scores of PROs, as measured by the validated instruments Functional Assessment of Cancer Therapy-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	Overall mean changes in scores of PROs, as measured by the validated instruments 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	Overall mean changes in scores of PROs, as measured by the validated instruments 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	Overall mean changes in scores of PROs, as measured by the validated instruments 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".	Up to 5 years
Secondary	Overall mean changes in scores PROs, as measured by the validated Functional Assessment of Cancer - General (FACT-G) global population 5 (GP5) question	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 in score of the GP5 item in the participant 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