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

November 14, 2023 updated by: IGM Biosciences, Inc.

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

97

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Health
      • Fitzroy, Victoria, Australia, 3065
        • St. Vincent's Hospital Melbourne
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Linear Clinical Resaerch
  • Czechia
      • Praha 10, Czechia
        • Fakultni nemocnice Kralovske Vinohrady
  • France
      • Poitiers, France, 86000
        • CHU de Poitiers
      • Villejuif, France
        • Gustave Roussy
  • Italy
      • Bologna, Italy, 40138
        • Azienda Ospedaliero Universitaria di Bologna-Ematologia Bologna
    • BG
      • Bergamo, BG, Italy
        • Asst Papa Giovanni Xxiii
    • RM
      • Roma, RM, Italy
        • Fondazione Policlinico Universitario Agostino Gemelli
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center
  • Spain
      • Barcelona, Spain
        • Hospital de La Santa Creu i Sant Pau
      • Barcelona, Spain, 08025
        • Hospital Santa Creu i Sant Pau
      • Barcelona, Spain, 8003
        • Hospital del Mar
      • Barcelona, Spain
        • Institut Catala d'Oncologia
      • Madrid, Spain, 28040
        • START-Madrid: Fundacion Jimenez Diaz
      • Madrid, Spain, 28050
        • START-Madrid: Centro Integral Oncologico Clara Campal
  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope
    • Florida
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute (DFCI)
    • New York
      • New York, New York, United States, 10065
        • MSKCC
      • New York, New York, United States, 10016
        • NYU
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutch

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1a (Dose Escalation)
Subjects will receive imvotamab via intravenous (IV) infusion weekly. No longer enrolling.
Drug: imvotamab
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion.
Experimental: Phase 1a (Q3W)
Subjects will receive imvotamab via intravenous (IV) infusion every 3 weeks. No longer enrolling.
Drug: imvotamab
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion.
Experimental: Phase 1a (Prior bi-specific)
Subjects treated with prior bi-specifics will receive imvotamab via IV infusion weekly. No longer enrolling.
Drug: imvotamab
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion.
Experimental: 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.
Drug: imvotamab
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion.
Experimental: 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.
Drug: imvotamab
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion.
Experimental: Phase 1b (Combination)
Subjects will receive imvotamab via IV infusion weekly and loncastuximab tesirine via IV infusion every 3 weeks.
Drug: imvotamab
Subjects with r/r B-cell NHL will receive IGM-2323 via IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Frequency of Adverse Events
Time Frame: Baseline through approximately 30 days after last study treatment
Percentage of Adverse Events
Baseline through approximately 30 days after last study treatment
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)
Baseline up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective 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)
Baseline up to 5 years
Duration of Response (DOR)
Time Frame: Baseline up to 5 years
measured from time of initial response until documented tumor progression
Baseline up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IGM Biosciences, Inc.

Collaborators

ADC Therapeutics S.A.

Investigators

  • Study Director: Ibrahim Qazi, IGM Biosciences, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2019

Primary Completion (Estimated)

October 1, 2024

Study Completion (Estimated)

October 1, 2024

Study Registration Dates

First Submitted

September 4, 2019

First Submitted That Met QC Criteria

September 5, 2019

First Posted (Actual)

September 10, 2019

Study Record Updates

Last Update Posted (Actual)

November 15, 2023

Last Update Submitted That Met QC Criteria

November 14, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IGM-2323-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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