A Study of Imvotamab Monotherapy and in Combination in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04082936 |
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Recruitment Status :
Active, not recruiting
First Posted : September 10, 2019
Last Update Posted : November 15, 2023
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This is a Phase 1/2 study of imvotamab in adult subjects with relapsed or refractory B-cell Non-Hodgkin Lymphoma. This study will consist of a dose-escalation stage, a combination stage, and a randomized dose-expansion stage where subjects will be enrolled into indication-specific expansion cohorts. imvotamab 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 |
|---|---|---|
| Non-Hodgkin Lymphoma Follicular Lymphoma DLBCL Mantle Cell Lymphoma Marginal Zone Lymphoma | Drug: imvotamab | Phase 1 Phase 2 |
Imvotamab 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. Imvotamab is able to eliminate CD20-positive lymphoma cells by engaging T-cells and lymphoma cells, leading to T-cell dependent cellular cytotoxicity. Additionally, imvotamab 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 imvotamab 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).
For the combination stage, imvotamab will be combined with loncastuximab tesirine, a CD19-targeting antibody drug conjugate.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 97 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1/2 Open-label, Multicenter Study Evaluating the Safety and Pharmacokinetics of Imvotamab (IGM-2323) as a Single Agent and in Combination in Subjects With Relapsed/Refractory Non-Hodgkin Lymphomas |
| Actual Study Start Date : | September 30, 2019 |
| Estimated Primary Completion Date : | October 2024 |
| Estimated Study Completion Date : | October 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Phase 1a (Dose Escalation)
Subjects will receive imvotamab via intravenous (IV) infusion weekly. No longer enrolling.
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Drug: imvotamab
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion. |
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Experimental: Phase 1a (Q3W)
Subjects will receive imvotamab via intravenous (IV) infusion every 3 weeks. No longer enrolling.
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Drug: imvotamab
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion. |
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Experimental: Phase 1a (Prior bi-specific)
Subjects treated with prior bi-specifics will receive imvotamab via IV infusion weekly. No longer enrolling.
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Drug: imvotamab
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion. |
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Experimental: Phase 2 (DLBCL)
DLBCL subjects will receive imvotamab via IV infusion at a dose and schedule to be determined after reviewing all available response and safety data. No longer enrolling.
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Drug: imvotamab
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion. |
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Experimental: Phase 2 (FL)
FL subjects will receive imvotamab via IV infusion at a dose and schedule to be determined after reviewing all available response and safety data. No longer enrolling.
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Drug: imvotamab
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion. |
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Experimental: Phase 1b (Combination)
Subjects will receive imvotamab via IV infusion weekly and loncastuximab tesirine via IV infusion every 3 weeks.
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Drug: imvotamab
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion. |
- Overall Frequency of Adverse Events [ Time Frame: Baseline through approximately 30 days after last study treatment ]Percentage of Adverse Events
- Overall Response Rate (ORR) [ Time Frame: Baseline up to 5 years ]Percentage of measurable disease in subjects who have achieved either complete response (CR) or partial response (PR)
- Objective Response Rate (ORR) [ Time Frame: 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) [ Time Frame: Baseline up to 5 years ]measured from time of initial response until documented tumor progression
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 imvotamab 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 imvotamab, and prior CAR-T therapy only allowed with Medical Monitor approval.
- Concurrent serious co-morbidities that could limit patients full participation and compliance.
- Prior CD-targeting bispecific antibodies.
- Prior loncastuximab tesirine.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04082936
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| Study Director: | Ibrahim Qazi | IGM Biosciences, Inc. |
| Responsible Party: | IGM Biosciences, Inc. |
| ClinicalTrials.gov Identifier: | NCT04082936 |
| Other Study ID Numbers: |
IGM-2323-001 |
| First Posted: | September 10, 2019 Key Record Dates |
| Last Update Posted: | November 15, 2023 |
| Last Verified: | November 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Lymphoma Non-Hodgkin Lymphoma DLBCL Follicular Lymphoma relapsed or refractory |
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Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphoma, Mantle-Cell Lymphoma, B-Cell, Marginal Zone Neoplasms by Histologic Type |
Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, B-Cell |