A Study of Imvotamab Monotherapy and in Combination in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma

Mantle Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04082936
• Other study ID #: IGM-2323-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 30, 2019
• Est. completion date: October 2024

Study information

• Verified date: November 2023
• Source: IGM Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 97
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• DLBCL
• Follicular Lymphoma
• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Mantle Cell Lymphoma
• Marginal Zone Lymphoma
• Non-Hodgkin Lymphoma

Intervention

Drug:
• imvotamab
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion.

Locations

Country	Name	City	State
Australia	Monash Health	Clayton	Victoria
Australia	St. Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Linear Clinical Resaerch	Nedlands	Western Australia
Czechia	Fakultní nemocnice Královské Vinohrady	Praha 10
France	CHU de Poitiers	Poitiers
France	Gustave Roussy	Villejuif
Italy	ASST Papa Giovanni XXIII	Bergamo	BG
Italy	Azienda Ospedaliero Universitaria di Bologna-Ematologia Bologna	Bologna
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma	RM
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Del Mar	Barcelona
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Institut Catala d'Oncologia	Barcelona
Spain	START-Madrid: Centro Integral Oncologico Clara Campal	Madrid
Spain	START-Madrid: Fundacion Jimenez Diaz	Madrid
United States	Dana Farber Cancer Institute (DFCI)	Boston	Massachusetts
United States	City of Hope	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Tennessee Oncology	Nashville	Tennessee
United States	MSKCC	New York	New York
United States	NYU	New York	New York
United States	Fred Hutch	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
IGM Biosciences, Inc.	ADC Therapeutics S.A.

Countries where clinical trial is conducted

United States,  Australia,  Czechia,  France,  Italy,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Frequency of Adverse Events	Percentage of Adverse Events	Baseline through approximately 30 days after last study treatment
Primary	Overall Response Rate (ORR)	Percentage of measurable disease in subjects who have achieved either complete response (CR) or partial response (PR)	Baseline up to 5 years
Secondary	Objective Response Rate (ORR)	Percentage of measurable disease in subjects who have achieved either complete response (CR) or partial response (PR)	Baseline up to 5 years
Secondary	Duration of Response (DOR)	measured from time of initial response until documented tumor progression	Baseline up to 5 years