Non-Hodgkin LymphomaPhase 1/2NCT04082936
A Study of Imvotamab Monotherapy and in Combination in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma
A Phase 1/2 study testing imvotamab in people with Non-Hodgkin Lymphoma and Follicular Lymphoma, run by IGM Biosciences, Inc. at 26 sites in 7 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin Lymphoma, Follicular Lymphoma, DLBCL
- What is being tested?
- imvotamab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 97 participants
- Where
- 26 sitesin 7 countries
- Study dates
- 30 Sep 2019to 22 Feb 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- > 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.
Who cannot join
- 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.
Trial locations and contacts
26 sites in 7 countries.
26 sites in 7 countries
United States9 sites
Dana Farber Cancer Institute (DFCI)
Boston, Massachusetts, 02215
City of Hope
Duarte, California, 91010
MD Anderson Cancer Center
Houston, Texas, 77030
Norton Cancer Institute
Louisville, Kentucky, 40202
Tennessee Oncology
Nashville, Tennessee, 37203
NYU
New York, New York, 10016
MSKCC
New York, New York, 10065
Fred Hutch
Seattle, Washington, 98109
Moffitt Cancer Center
Tampa, Florida, 33612
Spain6 sites
Hospital Santa Creu i Sant Pau
Barcelona, 08025
Hospital Del Mar
Barcelona, 8003
Hospital de la Santa Creu i Sant Pau
Barcelona
Institut Catala d'Oncologia
Barcelona
START-Madrid: Fundacion Jimenez Diaz
Madrid, 28040
START-Madrid: Centro Integral Oncologico Clara Campal
Madrid, 28050
Australia3 sites
Monash Health
Clayton, Victoria, 3168
St. Vincent's Hospital Melbourne
Fitzroy, Victoria, 3065
Linear Clinical Resaerch
Nedlands, Western Australia, 6009
Italy3 sites
ASST Papa Giovanni XXIII
Bergamo, BG
Azienda Ospedaliero Universitaria di Bologna-Ematologia Bologna
Bologna, 40138
Fondazione Policlinico Universitario Agostino Gemelli
Roma, RM
South Korea2 sites
Seoul National University Hospital
Seoul, 03080
Samsung Medical Center
Seoul, 06351
About this study
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
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.
Read the detailed description
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.
- Conditions
- Non-Hodgkin Lymphoma, Follicular Lymphoma, DLBCL, Mantle Cell Lymphoma, Marginal Zone Lymphoma
- Being tested
- imvotamab
- Keywords
- Lymphoma, Non-Hodgkin Lymphoma, DLBCL, Follicular Lymphoma, relapsed or refractory
- Medical subject headings
- Lymphoma, Non-Hodgkin, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
imvotamabDrug
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1a (Dose Escalation) | Experimental | Subjects will receive imvotamab via intravenous (IV) infusion weekly. No longer enrolling. Receives: Drug: imvotamab |
| Phase 1a (Q3W) | Experimental | Subjects will receive imvotamab via intravenous (IV) infusion every 3 weeks. No longer enrolling. Receives: Drug: imvotamab |
| Phase 1a (Prior bi-specific) | Experimental | Subjects treated with prior bi-specifics will receive imvotamab via IV infusion weekly. No longer enrolling. Receives: Drug: imvotamab |
| Phase 2 (DLBCL) | Experimental | 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. Receives: Drug: imvotamab |
| Phase 2 (FL) | Experimental | 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. Receives: Drug: imvotamab |
| Phase 1b (Combination) | Experimental | Subjects will receive imvotamab via IV infusion weekly and loncastuximab tesirine via IV infusion every 3 weeks. Receives: Drug: imvotamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Frequency of Adverse Events
Percentage of Adverse Events
Measured: Baseline through approximately 30 days after last study treatment
Overall Response Rate (ORR)
Percentage of measurable disease in subjects who have achieved either complete response (CR) or partial response (PR)
Measured: Baseline up to 5 years
Secondary outcomes (2)
Objective Response Rate (ORR)
Percentage of measurable disease in subjects who have achieved either complete response (CR) or partial response (PR)
Measured: Baseline up to 5 years
Duration of Response (DOR)
measured from time of initial response until documented tumor progression
Measured: Baseline up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2019
- Study start30 Sep 2019
- Primary completion16 Feb 2024
- Study completion22 Feb 2024
Why it stopped: Strategic Pipeline Prioritization: Clinical development of imvotamab in autoimmune diseases prioritized.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- IGM Biosciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ADC Therapeutics S.A.
- Responsible party
- Sponsor
- Investigators
- IGM Biosciences, Study director, IGM Biosciences, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04082936
- Sponsor's protocol ID
- IGM-2323-001
- Status last verified
- Jul 2024
- First submitted
- 4 Sep 2019
- Last updated
- 24 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04082936
- Acronym / sponsor ID
- IGM-2323-001
- Conditions
- Non-Hodgkin Lymphoma, Follicular Lymphoma, DLBCL, Mantle Cell Lymphoma, Marginal Zone Lymphoma
- Keywords
- Lymphoma, Non-Hodgkin Lymphoma, DLBCL, Follicular Lymphoma, relapsed or refractory
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Strategic Pipeline Prioritization: Clinical development of imvotamab in autoimmune diseases prioritized.
- Enrolment
- 97 participants (actual)
- Lead sponsor
- IGM Biosciences, Inc.Industry (pharma, biotech, devices)
- Collaborators
- ADC Therapeutics S.A.
- Study start
- 30 Sep 2019 (actual)
- Primary completion
- 16 Feb 2024 (actual)
- Study completion
- 22 Feb 2024 (actual)
- First posted
- 10 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Phase 1a (Dose Escalation) | Experimental | Drug: imvotamabSubjects will receive imvotamab via intravenous (IV) infusion weekly. No longer enrolling. |
| Phase 1a (Q3W) | Experimental | Drug: imvotamabSubjects will receive imvotamab via intravenous (IV) infusion every 3 weeks. No longer enrolling. |
| Phase 1a (Prior bi-specific) | Experimental | Drug: imvotamabSubjects treated with prior bi-specifics will receive imvotamab via IV infusion weekly. No longer enrolling. |
| Phase 2 (DLBCL) | Experimental | Drug: imvotamabDLBCL 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. |
| Phase 2 (FL) | Experimental | Drug: imvotamabFL 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. |
| Phase 1b (Combination) | Experimental | Drug: imvotamabSubjects will receive imvotamab via IV infusion weekly and loncastuximab tesirine via IV infusion every 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- > 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
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| imvotamabSubjects with r/r B-cell NHL will receive IGM-2323 via IV infusion. | Drug | Phase 1a (Dose Escalation), Phase 1a (Prior bi-specific), Phase 1a (Q3W), Phase 1b (Combination), Phase 2 (DLBCL), Phase 2 (FL) |
Primary outcome
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)
2 secondary outcomes
Objective Response Rate (ORR)
Time frame: Baseline up to 5 years
Duration of Response (DOR)
Time frame: Baseline up to 5 years
Results and safety
The study was stopped early (reason given: Strategic Pipeline Prioritization: Clinical development of imvotamab in autoimmune diseases prioritized.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
IGM Biosciences study director
IGM Biosciences, Inc.
26 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing imvotamab in people with Non-Hodgkin Lymphoma and Follicular Lymphoma, run by IGM Biosciences, Inc. at 26 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, Spain, Australia, Italy, France and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Strategic Pipeline Prioritization: Clinical development of imvotamab in autoimmune diseases prioritized.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Frequency of Adverse Events (time frame: Baseline through approximately 30 days after last study treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2024.