A Study of Imvotamab Monotherapy and in Combination in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma
- Conditions
- Non-Hodgkin LymphomaFollicular LymphomaDLBCLMarginal Zone LymphomaMantle Cell Lymphoma
- Interventions
- Registration Number
- NCT04082936
- Lead Sponsor
- IGM Biosciences, Inc.
- Brief 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. 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 97
- > 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1a (Q3W) imvotamab Subjects will receive imvotamab via intravenous (IV) infusion every 3 weeks. No longer enrolling. Phase 1a (Dose Escalation) imvotamab Subjects will receive imvotamab via intravenous (IV) infusion weekly. No longer enrolling. Phase 1a (Prior bi-specific) imvotamab Subjects treated with prior bi-specifics will receive imvotamab via IV infusion weekly. No longer enrolling. Phase 2 (DLBCL) imvotamab 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. Phase 1b (Combination) imvotamab Subjects will receive imvotamab via IV infusion weekly and loncastuximab tesirine via IV infusion every 3 weeks. Phase 2 (FL) imvotamab 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.
- Primary Outcome Measures
Name Time Method 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)
Overall Frequency of Adverse Events Baseline through approximately 30 days after last study treatment Percentage of Adverse Events
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) Baseline up to 5 years measured from time of initial response until documented tumor progression
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)
Trial Locations
- Locations (26)
Linear Clinical Resaerch
🇦🇺Nedlands, Western Australia, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
City of Hope
🇺🇸Duarte, California, United States
NYU
🇺🇸New York, New York, United States
MSKCC
🇺🇸New York, New York, United States
ASST Papa Giovanni XXIII
🇮🇹Bergamo, BG, Italy
CHU de Poitiers
🇫🇷Poitiers, France
Gustave Roussy
🇫🇷Villejuif, France
Fakultní nemocnice Královské Vinohrady
🇨🇿Praha 10, Czechia
Fondazione Policlinico Universitario Agostino Gemelli
🇮🇹Roma, RM, Italy
Azienda Ospedaliero Universitaria di Bologna-Ematologia Bologna
🇮🇹Bologna, Italy
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Del Mar
🇪🇸Barcelona, Spain
Hospital Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
START-Madrid: Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Institut Catala d'Oncologia
🇪🇸Barcelona, Spain
START-Madrid: Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Dana Farber Cancer Institute (DFCI)
🇺🇸Boston, Massachusetts, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Fred Hutch
🇺🇸Seattle, Washington, United States
St. Vincent's Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia