A Study to Assess the Anti-Tumor Activity and Safety of Odronextamab in Patients With B-cell Non-Hodgkin Lymphoma That Have Been Previously Treated

B-cell Non-Hodgkin Lymphoma (NHL) Clinical Trial

— ELM-2  

Official title:

An Open-Label Study to Assess the Anti-Tumor Activity and Safety of REGN1979, an Anti CD20 x Anti-CD3 Bispecific Antibody, in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03888105
• Other study ID #: R1979-ONC-1625
• Secondary ID: 2017-002139-41
• Status: Recruiting
• Phase: Phase 2
• Start date: November 13, 2019
• Est. completion date: February 5, 2028

Study information

• Verified date: March 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

Primary objective is to assess the anti-tumor activity of single agent odronextamab as measured by the objective response rate (ORR) according to the Lugano Classification of response in malignant lymphoma (Cheson, 2014) and as assessed by independent central review in each of the following B-cell non-Hodgkin lymphoma (B-NHL) subgroups:

• In patients with follicular lymphoma (FL) grade 1-3a *1,2

• In patients with diffuse large B-cell lymphoma (DLBCL) *1,2

• In patients with mantle cell lymphoma (MCL) that has relapsed after or is refractory to a BTK inhibitor. This cohort will also include patients who have relapsed or have disease refractory to prior systemic therapy, or patients who have demonstrated intolerance to BTK inhibitor therapy, and who have progressed after other systemic therapy.

• In patients with marginal zone lymphoma (MZL) *1

• In patients with other B-NHL subtypes *1

Secondary objectives are:

• To assess the anti-tumor activity of single agent odronextamab in each of 5 disease-specific cohorts, as measured by:

• ORR according to the Lugano Classification and as assessed by local investigator evaluation

• Complete response (CR) rate according to the Lugano Classification and as assessed local by local investigator evaluation and independent central review

• Progression-free survival (PFS)*3

• Overall survival (OS)

• Duration of response (DOR)*3

• Disease control rate (DCR)*3

• To evaluate the safety and tolerability of odronextamab

• To assess the pharmacokinetics (PK) of odronextamab

• To assess the immunogenicity of odronextamab

• To assess the effect of odronextamab on patient reported outcomes, including health-related quality of life (HRQL), as measured by the validated instruments European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym), and EuroQoL 5 Dimensions 3 Levels (EQ-5D-3L)

• 1 that has relapsed after or is refractory to at least 2 prior lines of systemic therapy

• 2 including an anti-CD20 antibody and an alkylating agent

• 3 according to Lugano Classification and as assessed by independent central review and local investigator evaluation

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 512
• Est. completion date: February 5, 2028
• Est. primary completion date: December 19, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• For the FL grade 1-3a cohort only: Central histopathologic confirmation of the FL Grade 1 to 3a diagnosis must be obtained before study enrollment. Patients with FL grade 3b are ineligible for this cohort but may be included in the "other B-NHL" cohort. Follicular lymphoma subtyping is based on the World Health Organization (WHO) classification (Swerdlow, 2017).

• Disease-specific cohorts that has relapsed after or is refractory to at least 2 prior lines of systemic therapy as defined in the protocol

• DLBCL cohort: Patients with DLBCL that has relapsed after or is refractory to at least 2 prior lines of systemic therapy as defined in the protocol

• MCL after BTK inhibitor therapy cohort: New enrollment is paused until further notice

• MZL cohort: Patients with MZL that have relapsed or is refractory to at least 2 prior lines of systemic therapy.

• Other B-NHL cohort: Patients with B-NHL other than FL grade 1-3a, DLBCL, MCL, or MZL that has relapsed after or is refractory to at least 2 prior lines of systemic therapy as defined in the protocol. New enrollment stopped for patients with Burkitt lymphoma and Burkitt-like lymphoma.

• Patients should in the judgment of the investigator require systemic therapy for lymphoma at the time of study enrollment

• Measurable disease on cross sectional imaging as defined in the protocol documented by diagnostic imaging (computed tomography (CT), or magnetic resonance imaging (MRI)

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Adequate bone marrow, hepatic, and renal function as defined in the protocol

Key Exclusion Criteria:

• Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS Non-Hodgkin Lymphoma (NHL) (suspected CNS lymphoma should be evaluated by lumbar puncture, as appropriate, in addition to the mandatory head CT or MRI).

• Treatment with any systemic anti-lymphoma therapy within 5 half-lives or within 28 days prior to first administration of study drug, whichever is shorter.

• History of allogeneic stem cell transplantation

• Prior treatment with any chimeric antigen receptor T-cell (CAR-T) therapy

• Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone or anti-inflammatory equivalent within 72 hours of start of study drug

• History of neurodegenerative condition or CNS movement disorder. Patients with a history of seizure within 12 months prior to study enrollment are excluded

• Another malignancy except B-NHL in the past 5 years, with the exception of non-melanoma skin cancer that has undergone potentially curative therapy or in situ cervical carcinoma, or any other tumor that has been deemed to be effectively treated with definitive local control and with curative intent.

• Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; cytomegalovirus (CMV) infection as noted by detectable levels on a blood polymerase chain reaction (PCR) assay as defined in the protocol or other uncontrolled infections

• Known hypersensitivity to both allopurinol and rasburicase

• Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Related Conditions & MeSH terms

• B-cell Non-Hodgkin Lymphoma (NHL)
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Odronextamab
Administered by intravenous (IV) infusion

Locations

Country	Name	City	State
Australia	Border Medical Oncology, Albury Wodonga Regional Cancer Centre	East Albury
Australia	Epworth Hospital	East Melbourne
Australia	Penninsula & South Eastern Haemotology and Oncology Group	Frankston
Australia	Andrew Love Cancer Center	Geelong
Australia	Olivia Newton John Cancer Centre	Heidelberg
Australia	The Tweed Hospital	Murdoch
Australia	Royal Perth Hospital	Perth
Australia	Andrew Love Cancer Center	Tweed Heads
Canada	Cross Cancer Center	Edmonton	Alberta
Canada	QEII Health Science Center	Halifax	Nova Scotia
China	Peking Union Medical College Hospital	Beijing
China	Peking University Cancer Hospital (Beijing Cancer Hospital) (Beijing Institute for Cancer Research)	Beijing	Beijing
China	Peking University Third Hospital	Beijing
China	Sun Yat-Sen University Cancer Center (Cancer Prevention and Treatment Center, Sun Yat-sen University)	Canton
China	The First Bethune Hospital Of Jilin University	Changchun	Jilin
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Second Affiliated Hospital of Army Medical University, PLA	Chongqing
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Heilongjiang
China	Fudan University Cancer Hospital	Shanghai
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences	Tianjin
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin
China	Renmin Hospital of Wuhan University	Wuhan
China	Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Wuhan Hubei Province
China	The First Affiliated Hospital of Xi 'an Jiaotong University	Xi'an
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
France	CHU de Caen	Caen
France	Hospital Henri Mondor	Créteil
France	Hopital Huriez-CHRU Lille	Lille
France	CHU de Nantes	Nantes
France	Hopital de la Pitie Salpetriere	Paris
France	Hospital Saint-Louis	Paris
France	CHU Haut Leveque	Pessac
France	Centre Hospitalier Lyon Sud	Pierre Bénite
France	Centre Hospitalier Universitaire (CHU) de Poitiers	Poitiers
Germany	Klinikum Chemnitz gGmbH Klinik fuer Innere Medizin III	Chemnitz
Germany	University Hospital Halle Saale	Halle
Germany	Kliniken Ostalb, Stauferklinikum	Mutlangen
Germany	Klinik fur Innere Medizin II Schwarzwald Baar Klinikum	Villingen-Schwenningen
Germany	Universitätsklinikum Würzburg	Wurzburg
Italy	Policlinico Sant'Orsola Malpipghi	Bologna
Italy	Azienda Ospedaliera Careggi	Firenze
Italy	Ospedale Di Livorno Usl6	Livorno
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	Fondazione IRCCS Ca' Grande Ospedale Maggiore Policlinico	Milano
Italy	AOU Maggiore della Carita	Novara
Italy	Santa Maria Della Misericordia Hospital	Perugia
Italy	Ospedale Santa Maria delle Croci	Ravenna
Italy	SC Ematologia Dip to Oncologico e Tecnologie Avanzate_ IRCCS - Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Struttura Complessa di Ematologia e Trapianto di cellule staminali emopoietiche _ IRCCS Casa Sollievo della Sofferenza	San Giovanni Rotondo
Italy	A.O. Santa Maria	Terni
Italy	Ospedale dell'Angelo	Varese
Italy	Ospedale DellAngelo Di Mestre Umberto I	Venice
Japan	Chiba Cancer Center	Chiba
Japan	National Cancer Center Hospital	Chuo ku
Japan	National Hospital Organization National Kyushu Cancer Center	Fukuoka-shi	Hukuoka
Japan	Tokai University Hospital	Isehara-Shi
Japan	National Cancer Center Hospital East	Kashiwa-shi	Chiba-ken
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	" University Hospital Kyoto Prefectural University of Medicine"	Kyoto City	Kyoto
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama	Ehime
Japan	Japanese Red Cross Nagasaki Genbaku Hospital	Nagasaki
Japan	Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital	Nagoya	Aiti
Japan	National Hospital Organization Nagoya Medical Center	Nagoya	Aiti
Japan	Osaka Metropolitan University Hospital	Osaka City
Japan	Saitama Medical University International Medical Center	Saitama
Japan	Yamagata University Hospital	Yamagata City
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu-si
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Szpitale Pomorskie spSp. Z.o.o.	Gdynia
Poland	Malopolskie Centrum Medyczne S.C	Krakow
Poland	Regeneron Study Site	Lodz
Poland	Apteka IHiT (Instytut Hematologii I Transfuzjologii	Warszawa
Poland	Instytut im. M. Sklodowskiej-Curie	Warszawa
Poland	Uniwersytecki Szpital Kliniczny	Wroclaw
Singapore	ICON-SOC Farrer Park Hospital	Singapore
Singapore	National University Hospital	Singapore
Singapore	Raffles Cancer Center	Singapore
Singapore	Singapore General Hospital	Singapore
Spain	Hospital Clinic I Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu I Sant Pau	Barcelona
Spain	Hospital Universitario Vall De'Hebron	Barcelona
Spain	Hospital Universitario Donostia	Donostia
Spain	Institut Català d'Oncologia	L'Hospitalet de llobregat
Spain	Fundacion Jimenez Diaz University Hospital	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario Quiron Salud Madrid	Madrid
Spain	MD Anderson Cancer Center	Madrid
Spain	Hospital Costa del Sol	Marbella
Spain	Hospital Son Espases	Palma
Spain	Hospital son Llatzer	Palma de Mallorca
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Taiwan	Kaosiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	Taipei Medical University - Shuang-Ho Hospital	New Taipei City
Taiwan	China Medical University Hospital	Taichung City
Taiwan	Chi-Mei Medical Center-Liuying	Tainan
Taiwan	National Cheng Kung University Hospital	Tainan City
Taiwan	Koo Foundation Sun Yat Sen Cancer Center	Taipei City
Taiwan	Mackay Memorial Hospital	Taipei City
Taiwan	National Taiwan University Hospital	Taipei City
Taiwan	Tri-Service General Hospital	Taipei City
Taiwan	Chang Gung Memorial Hospital	Taoyuan
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Kings College Hospital	London
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	The Royal Marsden Hospital	Sutton
United Kingdom	Royal Cornwall Hospital	Truro
United States	University of Michigan	Ann Arbor	Michigan
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Tufts Cancer Center	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Simmons Comprehensive Cancer Center	Dallas	Texas
United States	Brook Army Medical Center	Fort Sam Houston	Texas
United States	John Theurer Cancer Center Hackensack University Medical Center	Hackensack	New Jersey
United States	University of Iowa Hospital and Clinics	Iowa City	Iowa
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Morristown Medical Center	Morristown	New Jersey
United States	Weill Cornell Medical College	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	University/Academic Hospital Mayo Clinic	Rochester	Minnesota
United States	SSM Saint Louis University Hospital	Saint Louis	Missouri
United States	Stony Brook Hospital	Stony Brook	New York
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Poland,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR (FL grade 1-3a/MZL)	For each of the 5 disease-specific cohorts according to the Lugano Classification of response in malignant lymphoma (Cheson, 2014) and as assessed by independent central review.	From first patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study
Primary	ORR (DLBCL/MCL/Other B-NHL)	For each of the 5 disease-specific cohorts according to the Lugano Classification of response in malignant lymphoma (Cheson, 2014) and as assessed by independent central review.	From first patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study
Secondary	ORR (FL/MZL)	According to the Lugano Classification, as assessed by local investigator evaluation	First patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study.
Secondary	ORR (DLBCL/MCL/Other B-NHL)	According to the Lugano Classification, as assessed by local investigator evaluation	First patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study.
Secondary	CR rate (FL grade 1-3a/MZL)	According to the Lugano Classification and as assessed by local investigator evaluation and independent central review	First patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study.
Secondary	CR rate (DLBCL/MCL/Other B-NHL)	According to the Lugano Classification and as assessed by local investigator evaluation and independent central review	First patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study.
Secondary	PFS	According to the Lugano Classification and as assessed by independent central review and local investigator evaluation	First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Secondary	OS		First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Secondary	DOR	According to the Lugano Classification and as assessed by independent central review and local investigator evaluation	First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Secondary	DCR (FL grade 1-3a/MZL)	According to the Lugano Classification and as assessed by independent central review and local investigator evaluation	First patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study.
Secondary	DCR (DLBCL/MCL/Other B-NHL)	According to the Lugano Classification and as assessed by independent central review and local investigator evaluation	First patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study.
Secondary	Incidence and severity of treatment emergent adverse events (TEAEs)		First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Secondary	Pharmacokinetics: Concentration of odronextamab	End of infusion [EOI]; Concentration at a specified time t [Ct])	12 weeks following end of treatment
Secondary	Incidence of anti-drug antibodies (ADA) to odronextamab over time		12 weeks following end of treatment
Secondary	Titer of anti-drug antibodies to odronextamab over time		12 weeks following end of treatment
Secondary	Incidence of neutralizing antibodies (Nab) to odronextamab over time		12 weeks following end of treatment
Secondary	Changes in scores of patient-reported outcomes as measured by EORTC QLQ-C30	EORTC QLQ-C30 is a self-reported, 30-item generic questionnaire developed to assess 15 domains: global health status scale, five functional scales (physical, role, emotional, cognitive, and social functioning) and nine symptom scales (fatigue, nausea, vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties).	First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Secondary	Changes in scores of patient-reported outcomes as measured by FACT-Lym	Composed of the FACT-G plus the 15-item Lymphoma Subscale (LymS).	First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Secondary	Changes in scores of patient-reported outcomes as measured by EQ-5D-3L	The EQ-5D-3L is a standardized instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems.	First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose

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