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.
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
Drug | Synonyms | Arms |
---|
IGM-2323 | | Part 1: Dose-Escalation Phase |
IGM-2323 | | Part 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
Name | Type | Description | Interventions |
---|
Part 1: Dose-Escalation Phase | Experimental | Subjects 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. | |
Part 2: Dose-Expansion Phase | Experimental | Subjects 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. | |
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 3
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
Last Updated
May 19, 2021