A Study to Learn How Safe and Tolerable Odronextamab and Cemiplimab Are in Adult Patients With B-cell Malignancies (CLIO-1)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 1

Conditions: Relapsed/Refractory Aggressive B-Cell Lymphoma

Treatments: Drug: cemiplimab; Drug: odronextamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02651662

2015-001697-17 (EudraCT Number)

2023-508209-25-00 (Registry Identifier)

R1979-ONC-1504

Details and patient eligibility

About

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)

Enrollment: 62 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

62 participants in 2 patient groups

Dose escalation phase

Experimental group

Description:

Safety assessment of odronextamab in combination with cemiplimab and selection of recommended phase 2 dose (RP2D) regimen(s) for the combination of odronextamab and cemiplimab.

Treatment:

Drug: odronextamab

Drug: cemiplimab

Dose expansion phase

Experimental group

Description:

RP2D administration of the combination treatment.

Treatment:

Drug: odronextamab

Drug: cemiplimab