Clinical trial NCT04082936: A Study of Imvotamab Monotherapy and in Combination in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin Lymphoma
Follicular Lymphoma
DLBCL
Mantle Cell Lymphoma
Marginal Zone Lymphoma
Keywords: Lymphoma
Non-Hodgkin Lymphoma
DLBCL
Follicular Lymphoma
relapsed or refractory
Lead sponsor: IGM Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: ADC Therapeutics S.A.
First posted: 2019-09-10
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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). 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.

Primary outcomes:
measure: Overall Frequency of Adverse Events
timeFrame: Baseline through approximately 30 days after last study treatment
measure: Overall Response Rate (ORR)
timeFrame: Baseline up to 5 years
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Baseline up to 5 years
measure: Duration of Response (DOR)
timeFrame: Baseline up to 5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Dana Farber Cancer Institute (DFCI)
state: Massachusetts
city: New York
country: United States
facility: NYU
state: New York
city: New York
country: United States
facility: MSKCC
state: New York
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutch
state: Washington
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital Melbourne
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Resaerch
state: Western Australia
city: Praha 10
country: Czechia
facility: Fakultní nemocnice Královské Vinohrady
city: Poitiers
country: France
facility: CHU de Poitiers
city: Villejuif
country: France
facility: Gustave Roussy
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
state: BG
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
state: RM
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria di Bologna-Ematologia Bologna
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia
city: Madrid
country: Spain
facility: START-Madrid: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: START-Madrid: Centro Integral Oncologico Clara Campal
Study officials:
affiliation: IGM Biosciences, Inc.
name: IGM Biosciences
role: STUDY_DIRECTOR
References: