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A Safety and Pharmacokinetic Study of IGM-2323 in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma

NCT04082936

Description:

This is a Phase 1 study of IGM-2323 in adult subjects with relapsed or refractory B-cell Non-Hodgkin Lymphoma. This study will consist of a dose-escalation stage and a dose-expansion stage where subjects will be enrolled into indication-specific expansion cohorts. IGM-2323 will be administered intravenously (IV). Additional CD20-positive NHL histologies (e.g. MZL and MCL), may be allowed with Medical Monitor approval during the Dose-Escalation Phase of the study.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Safety and Pharmacokinetic Study of IGM-2323 in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma
  • Official Title: A Phase 1 Open-label, Multicenter Study Evaluating the Safety and Pharmacokinetics of Escalating Doses of IGM-2323 in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: IGM-2323-001
  • NCT ID: NCT04082936

Conditions

  • Non-Hodgkin Lymphoma
  • Follicular Lymphoma
  • DLBCL
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma

Interventions

DrugSynonymsArms
IGM-2323Part 1: Dose-Escalation Phase
IGM-2323Part 2: Dose-Expansion Phase

Purpose

This is a Phase 1 study of IGM-2323 in adult subjects with relapsed or refractory B-cell Non-Hodgkin Lymphoma. This study will consist of a dose-escalation stage and a dose-expansion stage where subjects will be enrolled into indication-specific expansion cohorts. IGM-2323 will be administered intravenously (IV). Additional CD20-positive NHL histologies (e.g. MZL and MCL), may be allowed with Medical Monitor approval during the Dose-Escalation Phase of the study.

Detailed Description

      IGM-2323 is an engineered bispecific IgM antibody for the treatment of patients with
      CD20-positive cancers. It contains ten high affinity binding domains for CD20, and one
      binding domain for CD3. IGM-2323 is able to eliminate CD20-positive lymphoma cells by
      engaging T-cells and lymphoma cells, leading to T-cell dependent cellular cytotoxicity.
      Additionally, IGM-2323 is also able to eliminate lymphoma cells by recruiting complement to
      the surface of lymphoma cells, leading to complement dependent cytotoxicity.

      In our preclinical studies, we observed activity against rituximab resistant cells carrying
      low levels of CD20. We have also observed much lower cytokine release with IGM-2323 relative
      to comparable IgG format bispecific T-cell engaging antibodies, which is expected to result
      in reduced risk of the serious adverse effects from cytokine release syndrome (CRS).
    

Trial Arms

NameTypeDescriptionInterventions
Part 1: Dose-Escalation PhaseExperimentalSubjects will receive IGM-2323 via intravenous (IV) infusion on Days 1, 8, and 15, of 21-day cycles. Subjects will be treated with 4 cycles (3 weeks each). Subjects benefiting from therapy can receive up to 8 cycles or longer with good response. Dose escalation will be guided by the observed incidence of DLTs at each dose level.
  • IGM-2323
Part 2: Dose-Expansion PhaseExperimentalSubjects will receive IGM-2323 via intravenous (IV) infusion at a RP2D dose and schedule to be determined after reviewing all available response and safety data.
  • IGM-2323

Eligibility Criteria

        Key Inclusion Criteria:

          -  > 18 years of age: ECOG PS 0 or 1

          -  Relapsed or Refractory Follicular Lymphoma (FL), and Diffuse Large B-cell Lymphoma
             (DLBCL), Mantle cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL) in dose escalation

          -  Relapsed or refractory to at least two prior systemic treatment regimens (must include
             anti-CD20 chemo-immunotherapy regimen).

          -  At least one bi-dimensionally measurable lesion (>1.5cm in it's longest dimension by
             computerized tomography (CT scan)

          -  Good organ function

          -  Not eligible for autologous stem cell transplant (DLBCL subjects), due to
             chemoresistant disease, medically unfit (organ function), or unwilling.

        Key Exclusion Criteria:

          -  Prior allogeneic transplant

          -  ASCT within 100 days prior to the first IGM-2323 administration.

          -  Prior treatment with CD3 engaging bispecific antibodies.

          -  Lack of response to prior treatment with CAR-T therapy, subjects with less than 6
             months from prior CAR-T therapy to first dose of IGM-2323, and prior CAR-T therapy
             only allowed with Medical Monitor approval.

          -  Concurrent serious co-morbidities that could limit patients' full participation and
             compliance
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Frequency of Adverse Events
Time Frame:Baseline through approximately 30 days after last study treatment
Safety Issue:
Description:Percentage of Adverse Events

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Baseline up to 1 year
Safety Issue:
Description:Percentage of measurable disease in subjects who have achieved either complete response (CR) or partial response (PR)
Measure:Duration of Response (DOR)
Time Frame:Baseline up to 4 years
Safety Issue:
Description:measured from time of initial response until documented tumor progression

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:IGM Biosciences, Inc.

Trial Keywords

  • Lymphoma
  • Non-Hodgkin Lymphoma
  • DLBCL
  • Follicular Lymphoma
  • relapsed or refractory

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