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

• ClinicalTrials.gov Identifier: NCT04082936
• Recruitment Status: Active, not recruiting
• First Posted: September 10, 2019
• Last Update Posted: November 15, 2023
• Sponsor: IGM Biosciences, Inc.
• Collaborator: ADC Therapeutics S.A.
• Information provided by (Responsible Party): IGM Biosciences, Inc.

Tracking Information

• First Submitted Date: September 4, 2019
• First Posted Date: September 10, 2019
• Last Update Posted Date: November 15, 2023
• Actual Study Start Date: September 30, 2019
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 16, 2022)

• Overall Frequency of Adverse Events [ Time Frame: Baseline through approximately 30 days after last study treatment ]
  Percentage of Adverse Events
• 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)

Original Primary Outcome Measures (submitted: September 5, 2019)

Overall Frequency of Adverse Events [ Time Frame: Baseline through approximately 30 days after last study treatment ]

Percentage of Adverse Events

Current Secondary Outcome Measures (submitted: February 16, 2022)

• 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)
• Duration of Response (DOR) [ Time Frame: Baseline up to 5 years ]
  measured from time of initial response until documented tumor progression

Original Secondary Outcome Measures (submitted: September 5, 2019)

• Objective Response Rate (ORR) [ Time Frame: Baseline up to 1 year ]
  Percentage of measurable disease in subjects who have achieved either complete response (CR) or partial response (PR)
• Duration of Response (DOR) [ Time Frame: Baseline up to 4 years ]
  measured from time of initial response until documented tumor progression

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

Drug: imvotamab

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

Study Arms

• Experimental: Phase 1a (Dose Escalation)
  Subjects will receive imvotamab via intravenous (IV) infusion weekly. No longer enrolling.
  Intervention: Drug: imvotamab
• Experimental: Phase 1a (Q3W)
  Subjects will receive imvotamab via intravenous (IV) infusion every 3 weeks. No longer enrolling.
  Intervention: Drug: imvotamab
• Experimental: Phase 1a (Prior bi-specific)
  Subjects treated with prior bi-specifics will receive imvotamab via IV infusion weekly. No longer enrolling.
  Intervention: Drug: imvotamab
• 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.
  Intervention: Drug: imvotamab
• 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.
  Intervention: Drug: imvotamab
• Experimental: Phase 1b (Combination)
  Subjects will receive imvotamab via IV infusion weekly and loncastuximab tesirine via IV infusion every 3 weeks.
  Intervention: Drug: imvotamab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 11, 2023): 97
• Original Estimated Enrollment (submitted: September 5, 2019): 160
• Estimated Study Completion Date: October 2024
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Czechia, France, Italy, Korea, Republic of, Spain, United States

Administrative Information

• NCT Number: NCT04082936
• Other Study ID Numbers: IGM-2323-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: IGM Biosciences, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: IGM Biosciences, Inc.
• Original Study Sponsor: Same as current
• Collaborators: ADC Therapeutics S.A.

Investigators

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

• PRS Account: IGM Biosciences, Inc.
• Verification Date: November 2023