A Safety and Pharmacokinetic Study of IGM-2323 in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
This is a Phase 1/2 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 randomized 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 1 (Dose Escalation) Subjects will receive IGM-2323 via intravenous (IV) infusion weekly. |
Drug: IGM-2323
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion.
|
| Experimental: Phase 1 (Q3W) Subjects will receive IGM-2323 via intravenous (IV) infusion every 3 weeks. |
Drug: IGM-2323
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion.
|
| Experimental: Phase 1 (Prior bi-specific) Subjects treated with prior bi-specifics will receive IGM-2323 via IV infusion weekly. |
Drug: IGM-2323
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion.
|
| Experimental: Phase 2 (DLBCL) DLBCL subjects will receive IGM-2323 via IV infusion at a dose and schedule to be determined after reviewing all available response and safety data. |
Drug: IGM-2323
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion.
|
| Experimental: Phase 2 (FL) FL subjects will receive IGM-2323 via IV infusion at a dose and schedule to be determined after reviewing all available response and safety data. |
Drug: IGM-2323
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion.
|
Outcome Measures
Primary Outcome Measures
- Overall Frequency of Adverse Events [Baseline through approximately 30 days after last study treatment]
Percentage of Adverse Events
- Overall Response Rate (ORR) [Baseline up to 5 years]
Percentage of measurable disease in subjects who have achieved either complete response (CR) or partial response (PR)
Secondary Outcome Measures
- Objective Response Rate (ORR) [Baseline up to 5 years]
Percentage of measurable disease in subjects who have achieved either complete response (CR) or partial response (PR)
- Duration of Response (DOR) [Baseline up to 5 years]
measured from time of initial response until documented tumor progression
Eligibility Criteria
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). FL/MZL may be enrolled with a least 2 prior systemic regimens which must include an anti-CD20, without the need for a prior chemotherapy 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.
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope | Duarte | California | United States | 91010 |
| 2 | Dana Farber Cancer Institute (DFCI) | Boston | Massachusetts | United States | 02215 |
| 3 | NYU | New York | New York | United States | 10016 |
| 4 | MSKCC | New York | New York | United States | 10065 |
| 5 | Tennessee Oncology | Nashville | Tennessee | United States | 37203 |
| 6 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 7 | Fred Hutch | Seattle | Washington | United States | 98109 |
| 8 | Monash Health | Clayton | Victoria | Australia | 3168 |
| 9 | St. Vincent's Hospital Melbourne | Fitzroy | Victoria | Australia | 3065 |
| 10 | Linear Clinical Resaerch | Nedlands | Western Australia | Australia | 6009 |
| 11 | Seoul National University Hospital | Seoul | Korea, Republic of | 03080 | |
| 12 | Asan Medical Center | Seoul | Korea, Republic of | 05505 | |
| 13 | Samsung Medical Center | Seoul | Korea, Republic of | 06351 |
Sponsors and Collaborators
- IGM Biosciences, Inc.
Investigators
- Study Director: Ibrahim Qazi, IGM Biosciences, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IGM-2323-001