Study to Investigate the Safety and Tolerability of Odronextamab in Patients With CD20+ B-Cell Malignancies

Chronic Lymphocytic Leukemia Clinical Trial

— ELM-1  

Official title:

An Open-Label, Multi-Center Phase 1 Study to Investigate the Safety and Tolerability of REGN1979, an Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody, in Patients With CD20+ B-Cell Malignancies Previously Treated With CD20-Directed Antibody Therapy (ELM-1)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02290951
• Other study ID #: R1979-HM-1333
• Secondary ID: 2015-004491-30
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 9, 2015
• Est. completion date: December 2, 2025

Study information

• Verified date: September 2023
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study has two parts with distinct study objectives and study design. In part A, odronextamab is studied as an intravenous (IV) administration with a dose escalation and a dose expansion phase for B-NHL and CLL. The dose escalation phase for B-NHL and the CLL study are closed at the time of protocol amendment 17. In part B, odronextamab is studied as a subcutaneous (SC) administration with a dose finding and a dose expansion phase for B-NHL.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: December 2, 2025
• Est. primary completion date: December 2, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Have documented CD20+ B-cell malignancy, with active disease not responsive to prior therapy, for whom no standard of care options exists, and for whom treatment with an anti-CD20 antibody may be appropriate:

• Part A (IV administration) B-NHL confirmed by National Cancer Institute (NCI) working group criteria

• Part B (SC administration): Confirmed diagnosis of B-NHL requiring therapy as defined by WHO classification 2017

2. Patients with B-NHL must have had prior treatment with an anti-CD20 antibody therapy. Patients with CLL (Part A only) are not required to have received prior treatment with an anti-CD20 antibody therapy as defined in the protocol.

• For the inclusion in the disease-specific expansion cohort enrolling DLBCL patients after failure of CAR-T therapy, the patient must have recovered from the toxicities of the lymphodepletion therapy and CAR-T infusion.

• For inclusion in Part B, patients must have FL grade 1-3a or DLBCL (with or without prior CAR-T) per the criteria above, and:

• Patients with FL grade 1-3a and DLBCL must have received at least 2 prior lines of systemic therapy, including an anti-CD20 antibody and an alkylating agent

3. All patients must have at least one bi-dimensionally measurable lesion =1.5 cm) documented by CT or MRI scan, if CT scan is not feasible.

4. Eastern Cooperative Oncology Group (ECOG) performance status =1

5. Life expectancy of at least 6 months

6. Adequate bone marrow function as described in the protocol

7. Adequate organ function as described in the protocol

8. Willingness to undergo mandatory tumor biopsy pretreatment, if in the opinion of the investigator, the patient has an accessible lesion that can be biopsied without significant risk to the patient.

9. Willing and able to comply with clinic visits and study-related procedures

10. Provide signed informed consent or legally acceptable representative

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 such as

• Epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis, or

• Evidence for presence of inflammatory lesions and/or vasculitis on cerebral MRI

3. Standard anti-lymphoma chemotherapy (non-biologic) or radiotherapy within 28 days prior to first administration of study drug

4. Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or cytomegalovirus (CMV) infection [(as noted by detectable levels on a blood polymerase chain reaction (PCR) assay)].

1. Patients with hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus deoxyribonucleic acid (DNA) that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted upon consultation with the physician managing the infection.

2. Patients who show detectable levels of CMV at screening will need to be treated with appropriate antiviral therapy and demonstrate at least 2 undetectable levels of CMV by PCR assay (at least 7 days apart) before being re-considered for eligibility.

5. Patients who have received a live vaccination within 28 days of first dose of study treatment

Note: Other protocol Inclusion/Exclusion criteria apply

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Non-Hodgkin Lymphoma

Intervention

Drug:
• Odronextamab multiple dose levels
Administered by intravenous (IV) infusion
• Odronextamab multiple dose levels
Administered by subcutaneous (SC) injection

Locations

Country	Name	City	State
France	CHU Hôpital Lyon Sud	Lyon
France	Centre Henri Becquerel	Rouen	Haute-Normandie
France	Institut Gustave Roussy	Villejuif	Île-de-France
Germany	Universitatsklinikum Wurzburg	Wurzburg	Bayern
Israel	Assuta Ashdod University Hospital	Ashdod	HaDarom
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Rambam Health Care Campus - Hematology and Bone Marrow Transplantation Institute	Haifa
Israel	Hadassah Medical Center	Jerusalem	Yerushalayim
Israel	Meir Medical Center	Kfar Saba	HaMerkaz
Israel	The Chaim Sheba Medical Center	Tel-Hashomer	HaMerkaz
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Royal Cornwall Hospitals NHS Trust	Truro	Cornwall
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute (Massachusetts General Hospital and Beth Israel)	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	University of California, Irvine	Orange	California
United States	Mayo Clinic	Rochester	Minnesota
United States	Stanford University	Stanford	California
United States	H. Lee Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  Germany,  Israel,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety/overall frequency of adverse events (AEs)	Part A and B	Up to 24 months
Primary	Safety/dose limiting toxicities (DLTs)	Part A and B	Up to 28 days
Primary	Antitumor activity as measured by the objective response rate (ORR)	Expansion Cohorts: • Diffuse large B-cell lymphoma (DLBCL) after failure of CAR-T therapy; Part A	Through study completion, an average of 24 months
Secondary	Pharmacokinetics (Concentration of odronextamab)	Peak plasma concentration (Cmax) of odronextamab; Part A and B	Up to 10 months
Secondary	Incidence of anti-drug antibodies (ADA) to odronextamab	Part A and B	Over time; up to approximately 15 months
Secondary	Titer of ADA to odronextamab	Part A and B	Over time; up to approximately 15 months
Secondary	Incidence of neutralizing antibodies (NAb) to odronextamab over time	Part A and B	Over time; Up to approximately 15 months
Secondary	Objective response rate (ORR)	For dose escalation portion and expansion cohorts: Aggressive lymphoma expansion cohort 2; FL grade 1-3a expansion cohorts 1 and 2 (Part A); For dose escalation and dose expansion cohorts: FL grade 1-3a; DLBCL; DLBCL post CAR T failure (Part B)	Through study completion, an average of 24 months
Secondary	Progression-free survival	Part A and B	Up to 48 months
Secondary	Overall Survival	Part A and B	Until death or lost to follow-up/ withdrawal, approximately up to 48 months
Secondary	Duration of response (DOR)	Part A and B	Until progression, approximately up to 48 months
Secondary	Minimal residual disease (MRD) for patients with CLL	Part A	Up to 24 months
Secondary	Duration of Complete Response (DOCR)	Part B	Until progression, approximately up to 48 months