Clinical trial NCT02290951: Study to Investigate the Safety and Tolerability of Odronextamab in Patients With CD20+ B-Cell Malignancies
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Non-Hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Keywords: Diffuse large B-cell lymphoma (DLBCL)
Follicular lymphoma (FL)
Aggressive lymphoma
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-11-14
Enrollment: 200
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety/overall frequency of adverse events (AEs)
timeFrame: Up to 24 months
measure: Safety/dose limiting toxicities (DLTs)
timeFrame: Up to 28 days
measure: Antitumor activity as measured by the objective response rate (ORR)
timeFrame: Through study completion, an average of 24 months
Secondary outcomes:
measure: Pharmacokinetics (Concentration of odronextamab)
timeFrame: Up to 10 months
measure: Incidence of anti-drug antibodies (ADA) to odronextamab
timeFrame: Over time; up to approximately 15 months
measure: Titer of ADA to odronextamab
timeFrame: Over time; up to approximately 15 months
measure: Incidence of neutralizing antibodies (NAb) to odronextamab over time
timeFrame: Over time; Up to approximately 15 months
measure: Objective response rate (ORR)
timeFrame: Through study completion, an average of 24 months
measure: Progression-free survival
timeFrame: Up to 48 months
measure: Overall Survival
timeFrame: Until death or lost to follow-up/ withdrawal, approximately up to 48 months
measure: Duration of response (DOR)
timeFrame: Until progression, approximately up to 48 months
measure: Minimal residual disease (MRD) for patients with CLL
timeFrame: Up to 24 months
measure: Duration of Complete Response (DOCR)
timeFrame: Until progression, approximately up to 48 months
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute (Massachusetts General Hospital and Beth Israel)
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Rouen
country: France
facility: Centre Henri Becquerel
state: Haute-Normandie
city: Lyon
country: France
facility: CHU Hôpital Lyon Sud
city: Villejuif
country: France
facility: Institut Gustave Roussy
state: Île-de-France
city: Wurzburg
country: Germany
facility: Universitatsklinikum Wurzburg
state: Bayern
city: Ashdod
country: Israel
facility: Assuta Ashdod University Hospital
state: HaDarom
city: Kfar Saba
country: Israel
facility: Meir Medical Center
state: HaMerkaz
city: Tel-Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
state: HaMerkaz
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
state: Yerushalayim
city: Haifa
country: Israel
facility: Rambam Health Care Campus - Hematology and Bone Marrow Transplantation Institute
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospitals NHS Trust
state: Cornwall
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Bannerji R, Arnason JE, Advani RH, Brown JR, Allan JN, Ansell SM, Barnes JA, O'Brien SM, Chavez JC, Duell J, Rosenwald A, Crombie JL, Ufkin M, Li J, Zhu M, Ambati SR, Chaudhry A, Lowy I, Topp MS. Odronextamab, a human CD20xCD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. Lancet Haematol. 2022 May;9(5):e327-e339. doi: 10.1016/S2352-3026(22)00072-2. Epub 2022 Apr 1.
citation: Zhu M, Olson K, Kirshner JR, Khaksar Toroghi M, Yan H, Haber L, Meagher C, Flink DM, Ambati SR, Davis JD, DiCioccio AT, Smith EJ, Retter MW. Translational findings for odronextamab: From preclinical research to a first-in-human study in patients with CD20+ B-cell malignancies. Clin Transl Sci. 2022 Apr;15(4):954-966. doi: 10.1111/cts.13212. Epub 2022 Jan 7.