Clinical trial NCT02651662: A Study to Learn How Safe and Tolerable Odronextamab and Cemiplimab Are in Adult Patients With B-cell Malignancies
Official title: A Phase 1 Study to Assess Safety and Tolerability of Odronextamab (REGN1979) an Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody, and Cemiplimab (REGN2810), an Anti-Programmed Death-1 Monoclonal Antibody in Patients With B-Cell Malignancies (CLIO-1)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed/Refractory Aggressive B-Cell Lymphoma
Keywords: B-Cell Non-Hodgkin Lymphoma (B-NHL)
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-01-11
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is researching a combination of 2 experimental drugs, referred to as "study drugs", called odronextamab (also known as REGN1979) and cemiplimab (also known as REGN2810). The study is focused on patients who have relapse/refractory aggressive B-cell lymphoma. The aim of the study is to see how safe and tolerable the study drugs are, and to define the recommended dose regimen for the combination with odronextamab.

This study is also looking at several other research questions, including:

* What side effects may happen from taking the study drugs
* How effective the study drugs are against the disease
* How much study drug is in the blood at different times
* Whether the body makes substances or protein called antibodies against the study drugs (that could make the drugs less effective or could lead to side effects)


Eligibility criteria: Key Inclusion Criteria:

1. Have documented CD20+ aggressive B-cell NHL that is either not responsive to or relapsed after at least 2 prior lines of systemic therapy, for whom treatment with an anti-CD20 antibody may be appropriate. In addition, prior treatments should at least contain an anti-CD20 antibody and an alkylating agent.
2. Must have at least 1 nodal lesion (≥1.5 cm), or at least one extranodal lesion with longest transverse diameter (LDi) greater than 1.0 cm, documented by diagnostic imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]).
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
4. Adequate bone marrow and hepatic function, as defined in the protocol
5. Willing and able to comply with clinic visits and study-related procedures
6. Provide signed informed consent

Key Exclusion Criteria:

1. Primary central nervous system (CNS) lymphoma, or known or suspected CNS involvement by non-primary CNS NHL
2. History of or current relevant CNS pathology, as described in the protocol
3. Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-mediated adverse events (iAEs)
4. Prior therapies, as described in the protocol
5. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection or other uncontrolled infection
6. Cytomegalovirus infection as noted by detectable levels on peripheral blood polymerase chain reaction (PCR) assay until the infection is well controlled.
7. Known hypersensitivity to both allopurinol and rasburicase
8. Pregnant or breastfeeding women
9. Women of childbearing potential, or men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose, as defined in the protocol
10. Patients prior diagnosis of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLTs) of cemiplimab in combination with odronextamab
timeFrame: Up to 28 days
measure: Incidence of treatment emergent adverse events (TEAEs) of cemiplimab in combination with odronextamab
timeFrame: Up to 18 months
measure: Severity of TEAEs of cemiplimab in combination with odronextamab
timeFrame: Up to 18 months
measure: Incidence of adverse events of special interest (AESIs) of cemiplimab in combination with odronextamab
timeFrame: Up to 18 months
measure: Severity of AESIs of cemiplimab in combination with odronextamab
timeFrame: Up to 18 months
Secondary outcomes:
measure: Odronextamab and cemiplimab concentrations in serum
timeFrame: Up to 18 months
measure: Incidence of anti-drug antibodies (ADAs) to odronextamab and cemiplimab over time
timeFrame: Up to 18 months
measure: Titer of ADAs to odronextamab and cemiplimab over time
timeFrame: Up to 18 months
measure: Incidence of neutralizing antibodies (Nabs) to odronextamab and cemiplimab over time
timeFrame: Up to 18 months
measure: Titer of Nabs to odronextamab and cemiplimab over time
timeFrame: Up to 18 months
measure: Overall response rate as assessed by investigator
timeFrame: Up to 18 months
measure: Complete response (CR) rate as assessed by investigator
timeFrame: Up to 18 months
measure: Duration of response as assessed by investigator
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: University of California Los Angeles Medical Center
state: California
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Dana Farber/Harvard Cancer Center - PO box 849168
state: Massachusetts
city: Boston
country: United States
facility: Harvard Medical School - Beth Israel Deaconess Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Cancer & Hematology Centers of Western Michigan
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: New York Presbyterian Hospital - Weill-Cornell
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Penn Medicine: University of Pennsylvania Health System
state: Pennsylvania
city: San Antonio
country: United States
facility: South Texas Oncology And Hematology
state: Texas
city: Salzburg
country: Austria
facility: Uniklinikum Salzburg (LKH) Universitatsklinik fur Innere Medizin III
city: Vienna
country: Austria
facility: Medical University Vienna
city: Heidelberg
country: Germany
facility: Regeneron Research Facility
state: Baden-Wurttemberg
city: Koln
country: Germany
facility: Universitatsklinikum Koln
state: North Rhine Westphalia
city: W rzburg
country: Germany
facility: Universitatsklinik Wurzburg, Med Klinik und Poliklinik II, Zentrum Innere Medizin
state: Wurzburg
city: Frankfurt am Main
country: Germany
facility: University Hospital Frankfurt
city: Jena
country: Germany
facility: Universitatsklinikum Jena
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig-Holstein, Campus Kiel
city: Beer Sheva
country: Israel
facility: Soroka
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Krakow
country: Poland
facility: Pratia MCM Krakow
state: Malopolska
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
state: Pomorskie
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Lodz
country: Poland
facility: Copernicus Memorial Hospital
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy Warszawa
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
state: Madrid
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Institut Catala dOncologia (ICO Hospitalet)
city: Madrid
country: Spain
facility: MD Anderson Cancer Center- Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: