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

• ClinicalTrials.gov Identifier: NCT02290951
• Recruitment Status: Active, not recruiting
• First Posted: November 14, 2014
• Last Update Posted: September 7, 2023
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: November 7, 2014
• First Posted Date: November 14, 2014
• Last Update Posted Date: September 7, 2023
• Actual Study Start Date: January 9, 2015
• Estimated Primary Completion Date: December 2, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 22, 2022)

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

• Original Primary Outcome Measures (submitted: November 11, 2014): Safety/overall frequency of adverse events [ Time Frame: Day 1 to 1 year ]

Current Secondary Outcome Measures (submitted: September 7, 2022)

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

Original Secondary Outcome Measures (submitted: November 11, 2014)

• Pharmacokinetics (Concentration of REGN1979) [ Time Frame: Day 1 to 1 year ]
  Peak plasma concentration (Cmax) of REGN1979
• Immunogenicity (Anti-REGN1979 antibodies) [ Time Frame: Day 1 to 1 year ]
  Anti-REGN1979 antibodies
• Overall response rate (ORR) [ Time Frame: Day 1 to 1 year ]
• Progression-free survival [ Time Frame: Day 1 to 1 year ]
• Overall Survival [ Time Frame: Day 1 to 1 year ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-Hodgkin Lymphoma
• Chronic Lymphocytic Leukemia

Intervention

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

Study Arms

• Experimental: Part A
  DLBCL post CAR-T
  Intervention: Drug: Odronextamab multiple dose levels
• Experimental: 1N Part B
  FL
  Intervention: Drug: Odronextamab multiple dose levels
• Experimental: 2N Part B
  DLBCL
  Intervention: Drug: Odronextamab multiple dose levels

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 5, 2023): 200
• Original Estimated Enrollment (submitted: November 11, 2014): 150
• Estimated Study Completion Date: December 2, 2025
• Estimated Primary Completion Date: December 2, 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Israel, United Kingdom, United States

Administrative Information

• NCT Number: NCT02290951
• Other Study ID Numbers: R1979-HM-1333; 2015-004491-30 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Regeneron Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Regeneron Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: September 2023