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ELM-1: Study to Investigate the Safety and Tolerability of Odronextamab in Patients With CD20+ B-Cell Malignancies

Sponsor
Regeneron Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT02290951
Collaborator
(none)
298
Enrollment
11
Locations
3
Arms
127.2
Anticipated Duration (Months)
27.1
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Odronextamab multiple dose levels
 Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
298 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Jan 9, 2015
Anticipated Primary Completion Date :
Aug 16, 2025
Anticipated Study Completion Date :
Aug 16, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part A

DLBCL post CAR-T

Drug: Odronextamab multiple dose levels
Administered by intravenous (IV) infusion or subcutaneous (SC) injection
Other Names:
  • REGN1979

    		•
    Experimental: 1N Part B

    FL

    Drug: Odronextamab multiple dose levels
    Administered by intravenous (IV) infusion or subcutaneous (SC) injection
    Other Names:
  • REGN1979

    		•
    Experimental: 2N Part B

    DLBCL

    Drug: Odronextamab multiple dose levels
    Administered by intravenous (IV) infusion or subcutaneous (SC) injection
    Other Names:
  • REGN1979

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Safety/overall frequency of adverse events (AEs) [Up to 24 months]

      Part A and B

    2. Safety/dose limiting toxicities (DLTs) [Up to 28 days]

      Part A and B

    3. 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

    1. Pharmacokinetics (Concentration of odronextamab) [Up to 10 months]

      Peak plasma concentration (Cmax) of odronextamab Part A and B

    2. Incidence of anti-drug antibodies (ADA) to odronextamab over time [Up to 15 months]

      Part A and B

    3. Titer of ADA to odronextamab over time [Up to 15 months]

      Part A and B

    4. Incidence of neutralizing antibodies (NAb) to odronextamab over time [Up to 15 months]

      Part A and B

    5. 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)

    6. Progression-free survival [Up to 48 months]

      Part A and B

    7. Overall Survival [Until death or lost to follow-up/ withdrawal, approximately up to 48 months]

      Part A and B

    8. Duration of response (DOR) [Until progression, approximately up to 48 months]

      Part A and B

    9. Minimal residual disease (MRD) for patients with CLL [Up to 24 months]

      Part A

    10. Duration of Complete Response (DOCR) [Until progression, approximately up to 48 months]

      Part B

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. Patients with B-NHL must have had prior treatment with an anti-CD20 antibody therapy.

    • 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

    1. 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.

    2. Eastern Cooperative Oncology Group (ECOG) performance status ≤1

    3. Life expectancy of at least 6 months

    4. Adequate bone marrow function as described in the protocol

    5. Adequate organ function as described in the protocol

    6. 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.

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

    8. 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

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

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

    3. 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.

    4. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California, Irvine Orange California United States 92868
    2 Stanford University Stanford California United States 94305
    3 Moffitt Cancer Center Tampa Florida United States 33612
    4 Dana Farber Cancer Institute (Massachusetts General Hospital and Beth Israel) Boston Massachusetts United States 02215
    5 Mayo Clinic Rochester Minnesota United States 55905
    6 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08901
    7 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    8 Weill Cornell Medical College New York New York United States 10065
    9 Centre Hospitalier Lyon-Sud Hospices Civils de Lyon Pierre Benite Cedex France 69495
    10 CHU Hôpital Lyon Sud Lyon France
    11 Universitatsklinikum Wurzburg Wurzburg Germany

    Sponsors and Collaborators

    • Regeneron Pharmaceuticals

    Investigators

    • Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Regeneron Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02290951
    Other Study ID Numbers:
    • R1979-HM-1333
    • 2015-004491-30
    First Posted:
    Nov 14, 2014
    Last Update Posted:
    Apr 29, 2022
    Last Verified:
    Apr 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Regeneron Pharmaceuticals
    Diffuse large B-cell lymphoma (DLBCL)
    Follicular lymphoma (FL)
    Aggressive lymphoma
    Additional relevant MeSH terms:
    Lymphoma
    Leukemia, Lymphocytic, Chronic, B-Cell

    Study Results

    No Results Posted as of Apr 29, 2022