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

Phase 1

Active, not recruiting

• Conditions: Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia
• Interventions: Drug: Odronextamab multiple dose levels

• Registration Number: NCT02290951
• Lead Sponsor: Regeneron Pharmaceuticals

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-11-07
• Study First Submitted QC: 2014-11-11
• Study First Posted: 2014-11-14
• Study Start: 2015-01-09
• Status Verified: 2024-10
• Last Update Submitted: 2024-11-04
• Last Update Posted: 2024-11-05
• Primary Completion: 2025-09-30
• Study Completion: 2025-09-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 200

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2N Part B	Odronextamab multiple dose levels	DLBCL
Part A	Odronextamab multiple dose levels	DLBCL post CAR-T
1N Part B	Odronextamab multiple dose levels	FL

Primary Outcome Measures

Name	Time	Method
Safety/overall frequency of adverse events (AEs)	Up to 24 months	Part A and B
Safety/dose limiting toxicities (DLTs)	Up to 28 days	Part A and B
Antitumor activity as measured by the objective response rate (ORR)	Through study completion, an average of 24 months	Expansion Cohorts: • Diffuse large B-cell lymphoma (DLBCL) after failure of CAR-T therapy; Part A

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (Concentration of odronextamab)	Up to 10 months	Peak plasma concentration (Cmax) of odronextamab; Part A and B
Titer of ADA to odronextamab	Over time; up to approximately 15 months	Part A and B
Incidence of neutralizing antibodies (NAb) to odronextamab over time	Over time; Up to approximately 15 months	Part A and B
Incidence of anti-drug antibodies (ADA) to odronextamab	Over time; up to approximately 15 months	Part A and B
Objective response rate (ORR)	Through study completion, an average of 24 months	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)
Progression-free survival	Up to 48 months	Part A and B
Overall Survival	Until death or lost to follow-up/ withdrawal, approximately up to 48 months	Part A and B
Duration of response (DOR)	Until progression, approximately up to 48 months	Part A and B
Minimal residual disease (MRD) for patients with CLL	Up to 24 months	Part A
Duration of Complete Response (DOCR)	Until progression, approximately up to 48 months	Part B

Trial Locations

Locations (22)

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

Institut Gustave Roussy; 🇫🇷 Villejuif, Île-de-France, France

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Weill Cornell Medical College; 🇺🇸 New York, New York, United States

Dana Farber Cancer Institute (Massachusetts General Hospital and Beth Israel); 🇺🇸 Boston, Massachusetts, United States

Hadassah Medical Center; 🇮🇱 Jerusalem, Yerushalayim, Israel

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Universitatsklinikum Wurzburg; 🇩🇪 Wurzburg, Bayern, Germany

CHU Hôpital Lyon Sud; 🇫🇷 Lyon, France

Meir Medical Center; 🇮🇱 Kfar Saba, HaMerkaz, Israel

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

Centre Henri Becquerel; 🇫🇷 Rouen, Haute-Normandie, France

Lady Davis Carmel Medical Center; 🇮🇱 Haifa, Israel

Stanford University; 🇺🇸 Stanford, California, United States

University of California, Irvine; 🇺🇸 Orange, California, United States

H. Lee Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

The Chaim Sheba Medical Center; 🇮🇱 Tel-Hashomer, HaMerkaz, Israel

Rambam Health Care Campus - Hematology and Bone Marrow Transplantation Institute; 🇮🇱 Haifa, Israel

Assuta Ashdod University Hospital; 🇮🇱 Ashdod, HaDarom, Israel

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Royal Cornwall Hospitals NHS Trust; 🇬🇧 Truro, Cornwall, United Kingdom