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

NCT ID: NCT04082936

Last Updated: 2024-07-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-30
• Study Completion Date: 2024-02-22

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.

Conditions

Non-Hodgkin Lymphoma; Follicular Lymphoma; DLBCL; Mantle Cell Lymphoma; Marginal Zone Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1a (Dose Escalation)

Subjects will receive imvotamab via intravenous (IV) infusion weekly. No longer enrolling.

Group Type: EXPERIMENTAL

imvotamab

Intervention Type: DRUG

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

Phase 1a (Q3W)

Subjects will receive imvotamab via intravenous (IV) infusion every 3 weeks. No longer enrolling.

Group Type: EXPERIMENTAL

imvotamab

Intervention Type: DRUG

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

Phase 1a (Prior bi-specific)

Subjects treated with prior bi-specifics will receive imvotamab via IV infusion weekly. No longer enrolling.

Group Type: EXPERIMENTAL

imvotamab

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

imvotamab

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

imvotamab

Intervention Type: DRUG

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

Phase 1b (Combination)

Subjects will receive imvotamab via IV infusion weekly and loncastuximab tesirine via IV infusion every 3 weeks.

Group Type: EXPERIMENTAL

imvotamab

Intervention Type: DRUG

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

Interventions

imvotamab

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

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ADC Therapeutics S.A.

INDUSTRY

Sponsor Role: collaborator

IGM Biosciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

IGM Biosciences

Role: STUDY_DIRECTOR

IGM Biosciences, Inc.

Locations

City of Hope

Duarte, California, United States

Moffitt Cancer Center

Tampa, Florida, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Dana Farber Cancer Institute (DFCI)

Boston, Massachusetts, United States

NYU

New York, New York, United States

MSKCC

New York, New York, United States

Tennessee Oncology

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Fred Hutch

Seattle, Washington, United States

Monash Health

Clayton, Victoria, Australia

St. Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

Linear Clinical Resaerch

Nedlands, Western Australia, Australia

Fakultní nemocnice Královské Vinohrady

Prague, , Czechia

CHU de Poitiers

Poitiers, , France

Gustave Roussy

Villejuif, , France

ASST Papa Giovanni XXIII

Bergamo, BG, Italy

Fondazione Policlinico Universitario Agostino Gemelli

Roma, RM, Italy

Azienda Ospedaliero Universitaria di Bologna-Ematologia Bologna

Bologna, , Italy

Seoul National University Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hospital Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Del Mar

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Institut Catala d'Oncologia

Barcelona, , Spain

START-Madrid: Fundacion Jimenez Diaz

Madrid, , Spain

START-Madrid: Centro Integral Oncologico Clara Campal

Madrid, , Spain

Countries

United States; Australia; Czechia; France; Italy; South Korea; Spain

Other Identifiers

IGM-2323-001

Identifier Type: -

Identifier Source: org_study_id