A Trial to Learn if Odronextamab Combined With Lenalidomide is Safe and Works Better Than Rituximab Combined With Lenalidomide in Participants With Follicular Lymphoma and Marginal Zone Lymphoma

Marginal Zone Lymphoma (MZL) Clinical Trial

— OLYMPIA-5  

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, in Combination With Lenalidomide Versus Rituximab in Combination With Lenalidomide Therapy in Relapsed/Refractory Participants With Follicular Lymphoma and Marginal Zone Lymphoma (OLYMPIA-5)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06149286
• Other study ID #: R1979-ONC-22102
• Secondary ID: 2022-503092-28-0
• Status: Recruiting
• Phase: Phase 3
• Start date: December 28, 2023
• Est. completion date: October 4, 2029

Study information

• Verified date: January 2024
• 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 patients who have one of two types of cancer: follicular lymphoma (FL) or marginal zone lymphoma (MZL) that has come back after treatment (called "relapsed"), or did not respond to treatment (called "refractory"). FL and MZL are subtypes of Non-Hodgkin 's lymphoma (NHL). This study will be made up of two parts (Part 1 not randomized, Part 2 randomized - controlled). The aim of Part 1 of the study is to see how safe and tolerable the study drug is when used in combination with lenalidomide, in participants with FL or MZL, and to determine the dose of the study drug to be used in Part 2 of this study. This combination is considered "first-in-human" as it has not been tested as a combination treatment in humans before. The aim of Part 2, of the study is to assess how the combination of odronextamab and lenalidomide works compared to the combination of rituximab and lenalidomide, (the current standard-of-care treatment for FL and/or MZL). 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 in combination with lenalidomide - 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: 470
• Est. completion date: October 4, 2029
• Est. primary completion date: October 4, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Local histologic confirmation of FL grade 1-3a or MZL (nodal, splenic, or extra nodal MZL) as assessed by the investigator.

2. Must have refractory disease or relapsed after at least 2 cycles of prior systemic chemo-immunotherapy or immunotherapy. Prior systemic therapy should have included at least one anti-cluster of differentiation 20 (CD20) monoclonal antibody and patient should meet indication for treatment.

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

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

5. Adequate hematologic and organ function.

Key Exclusion Criteria:

1. Primary central nervous system (CNS) lymphoma or known involvement (either current or prior history of CNS involvement) by non-primary CNS NHL.

2. Participants with histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma, or any histology other than FL grade 1-3a or MZL.

3. History of or current relevant CNS pathology, as described in the protocol.

4. A malignancy other than NHL unless the participant is adequately and definitively treated and is cancer free for at least 3 years, with the exception of localized prostate cancer treated with hormone therapy or local radiotherapy (ie, pellets), cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that was definitively treated.

5. 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.

6. Allergy/hypersensitivity to study drugs or excipients.

7. Active infection as defined in the protocol. Note: Other protocol-defined Inclusion/Exclusion criteria apply

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Marginal Zone Lymphoma (MZL)
• Relapsed/Refractory Follicular Lymphoma

Intervention

Drug:
• Odronextamab
Administered by intravenous (IV) infusion
• Lenalidomide
Administered orally (PO)
• Rituximab
Administered by IV infusion

Locations

Country	Name	City	State
Australia	Epworth Freemasons Hospital	East Melbourne	Victoria
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Belgium	Institut Jules Bordet, Hopital Universitaire de Bruxelles (HUB) Site Bordet	Brussels
Belgium	Universitair Ziekenhuis (UZ) Gent/ Ghent University Hospital	Gent	Oost-Vlaanderen
Belgium	CHU UCL Namur	Yvoir
Czechia	Fakultni Nemocnice Hradec Kralove	Hradec Kralove 5
France	Hopital Victor Dupouy Argenteuil	Argenteuil	Île De France
France	Policlinique Bordeaux Nord	Bordeaux Cedex	Gironde
France	Centre Hospitalier Metropole Savoie	Chambery	Savoie
France	Hopital Saint Vincent de Paul	Lille cedex	Nord
France	Nantes University Hospital	Nantes
France	Hopital Saint Antoine	Paris
France	Hopital Saint Louis	Paris	Cedex 10
France	CHU Bordeaux - GH Sud Haut-Leveque Francois Magendie Center	Pessac	Gironde
France	Chu Pontchaillou	Rennes
France	Centre Henri Becquerel	Rouen	Normandie
France	CHU Tours - Hopital Bretonneau	Tours	Centre-Val De Loire
Italy	FPO-IRCCS Candiolo Cancer Institute	Candiolo	Torino
Italy	Ospedale Policlinico San Martino IRCCS	Genova
Italy	Irccs Irst Meldola	Meldola (fc)	Forli-Cesena
Italy	IRCSS San Gerardo dei Tintori	Monza	Monza E Brianza
Italy	AOU Maggiore della Carita	Novara
Italy	Ospedale Santa Maria Delle Croci	Ravenna
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital (PNUH)	Busan
Korea, Republic of	Yeungnam University Medical Center	Daegu
Korea, Republic of	Gachon University Gil Medical Center	Seongnam-si	Gyeonggi-do
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University Of Korea St. Vincent's Hospital	Suwon
Korea, Republic of	Ulsan University Hospital	Ulsan
Malaysia	Hospital Ampang	Ampang	Selangor
Malaysia	Hospital Sultanah Aminah	Johor Bahru	Johor
Malaysia	Hospital Queen Elizabeth	Kota Kinabalu	Sabah
Poland	Pratia Onkologia Katowice	Katowice
Poland	Pratia McM Krakow	Krakow	Malopolska
Poland	Centrum Medyczne Pratia Poznan	Poznan	Wielkopolska
Spain	University Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Hospital HM Sanchinarro	Madrid
Spain	Hospital Universiterio Ramon Y Cajal	Madrid
Spain	Hospital Son Espases	Palma	Balearic Islands
Spain	Hospital Universitario Quironsalud Madrid	Pozuelo de Alarcón	Madrid
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hosptial Universitario Marques de Valdecilla	Santander	Cantabria
Spain	Hospital Universitario Virgen del Rocio	Seville
Spain	Hospital Universitario Doctor Peset	Valencia
Taiwan	National Taiwan University Hospital	Taipei City
Taiwan	Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital	Taoyuan City
Thailand	Chulalongkorn University	Bangkok	Krung Thep Maha Nakhon [Bangko]
Thailand	Siriraj Institute of Clinical Research (SICRES)	Bangkok
Thailand	Chiang Mai University	Chiang Mai
Turkey	Gazi University	Ankara
Turkey	Sakarya University Training and Research Hospital	Sakarya
Turkey	Namik Kemal Universitesi	Tekirdag	Suleymanpasa
Turkey	Ankara Research Hospital	Yenimahalle	Ankara
United Kingdom	University Hospitals Plymouth NHS Trust	Plymouth	Devon
United States	IU Simon Cancer Center	Indianapolis	Indiana
United States	Stony Brook University Medical Center- Cancer Center	Stony Brook	New York
United States	Prohealth Care, Inc	Waukesha	Wisconsin
United States	Clinical Research Alliance	Westbury	New York

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Czechia,  France,  Italy,  Korea, Republic of,  Malaysia,  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 lenalidomide	Part 1	Up to 35 days
Primary	Incidence of treatment emergent adverse events (TEAEs) for odronextamab in combination with lenalidomide	Part 1	Up to 2 years
Primary	Severity of TEAEs for odronextamab in combination with lenalidomide	Part 1	Up to 2 years
Primary	Progression-free survival (PFS) as assessed by independent central review (ICR) in participants with R/R FL and participants with indolent lymphoma	Part 2	Up to 5 years
Secondary	Odronextamab concentrations in serum	Part 1 and Part 2	Up to 30 months
Secondary	Incidence of anti-odronextamab antibodies (ADA) to odronextamab over time	Part 1 and Part 2	Up to 30 months
Secondary	Titer of ADAs to odronextamab over time	Part 1 and Part 2	Up to 30 months
Secondary	Incidence of neutralizing antibodies (NAbs) to odronextamab over time	Part 1 and Part 2	Up to 30 months
Secondary	Best overall response (BOR) as assessed by investigator review	Part 1 and Part 2	Up to 30 months
Secondary	Duration of response (DOR) as assessed by investigator review	Part 1 and Part 2	Up to 5 years
Secondary	PFS as assessed by investigator review	Part 1 and Part 2	Up to 5 years
Secondary	Complete response (CR) as assessed by ICR	Part 2	Up to 30 months
Secondary	BOR as assessed by ICR	Part 2	Up to 30 months
Secondary	Overall survival (OS)	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 review	Part 2	Up to 5 years
Secondary	DOR as assessed by ICR	Part 2	Up to 5 years
Secondary	Time to next anti-lymphoma treatment (TTNT)	Part 2	Up to 5 years
Secondary	Incidence of TEAEs for odronextamab in combination with lenalidomide versus R2	Part 2	Up to 2 years
Secondary	Severity of TEAEs for odronextamab in combination with lenalidomide versus R2	Part 2	Up to 2 years
Secondary	Overall change from baseline in patient reported outcomes (PROs) as measured by scores of European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQC30)	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 change from baseline in PROs as measured by scores of 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.	Up to 5 years
Secondary	Overall change from baseline in PROs as measured by scores of Patient Global Impression on 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 change from baseline in PROs as measured by scores of Patient Global Impression on 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 change from baseline in PROs as measured by scores of 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	Overall change from first assessment to end of treatment in score of the global population item 5 (GP5) items of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire	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).	Up to 5 years