Phase 1a/1b Study of Aplitabart (IGM-8444) Alone or in Combination in Participants With Relapsed, Refractory, or Newly Diagnosed Cancers

April 12, 2024 updated by: IGM Biosciences, Inc.

An Open-label, Multicenter, Phase 1a/1b Study of Aplitibart (IGM-8444) as a Single Agent and in Combination in Participants With Relapsed, Refractory, or Newly Diagnosed Cancers

This study is a first-in-human, Phase 1a/1b, multicenter, open-label study to determine the safety, tolerability, and pharmacokinetics of aplitabart as a single agent and in combination in participants with relapsed and/or refractory solid or hematologic cancers, as well as newly diagnosed cancers, and an open-label, randomized study of aplitabart+FOLFIRI+bevacizumab.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Participants will be enrolled in Phase 1a, which consists of two stages: a dose-escalation stage and an expansion stage. Aplitabart will be used as a single agent and in combination with numerous other agents where standard therapeutic regimens do not exist, have proven to be ineffective or intolerable, or are considered inappropriate.

Colorectal participants may be enrolled in Phase 1b, an open-label, randomized study of aplitabart+FOLFIRI+ bevacizumab.

Aplitabart will be investigated in numerous tumor types including all-comers solid tumors, colorectal carcinoma (CRC), sarcoma, non-Hodgkin's lymphoma (NHL), acute myeloid leukemia (AML), and chronic lymphocytic leukemia (CLL).

Aplitabart will be administered intravenously (IV).

An alternative dosing schedule may be evaluated.

Study Type

Interventional

Enrollment (Estimated)

430

Phase

  • 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
      • Kingswood, Australia, 2747
      • Southport, Australia, QLD 4215
      • Woodville South, Australia, 5011
        • Recruiting
        • Queen Elizabeth Hospital
        • Contact:
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
      • Wollongong, New South Wales, Australia, 2500
        • Recruiting
        • Southern Medical Day Care Centre
        • Contact:
    • Victoria
      • Melbourne, Victoria, Australia, 3052
        • Recruiting
        • Peter MacCallum Cancer Centre
        • Contact:
  • France
      • Bordeaux, France, 33076
        • Recruiting
        • Institut Bergonié
      • Dijon, France, 21000
        • Recruiting
        • Centre Georges Francois Leclerc
      • Paris, France, 75010
        • Recruiting
        • Saint Louis Hospital
      • Saint-Herblain, France, 44800
        • Recruiting
        • Institut de Cancérologie de l'Ouest
      • Villejuif, France, 94805
        • Recruiting
        • Gustave Roussy
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Recruiting
        • Seoul National University Hospital
        • Contact:
      • Seoul, Korea, Republic of, 03080
        • Recruiting
        • Asan Medical Center
        • Contact:
      • Soeul, Korea, Republic of
        • Recruiting
        • Severance Hospital - Yonsei Cancer Center
        • Contact:
          • Clinical Trial Recruitment
          • Phone Number: +82-2-2228-8137
          • Email: BEOMSH@yuhs.ac
    • Gangnam-gu
      • Seoul, Gangnam-gu, Korea, Republic of, 06351
    • Seongnam-si
      • Gyeonggi-do, Seongnam-si, Korea, Republic of, 13620
        • Recruiting
        • Seoul National University Bundang Hospital
        • Contact:
      • Gyeonggi-do, Seongnam-si, Korea, Republic of, 13620
        • Recruiting
        • Gachon University Gil Hospital
        • Contact:
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Vall d'Hebron Institut d'Oncologia
      • Madrid, Spain, 28027
        • Recruiting
        • Clinica Universidad de Navarra
      • Madrid, Spain, 28050
        • Recruiting
        • Madrid CIOCC - HM Universitario Sanchinnarro
      • Madrid, Spain, 28040
        • Recruiting
        • Madrid FJD
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic
    • California
      • Duarte, California, United States, 91010
      • Los Alamitos, California, United States, 90720
        • Recruiting
        • Cancer and Blood Specialty Clinic (CBSC)
        • Contact:
      • Los Angeles, California, United States, 90033
      • Los Angeles, California, United States, 90404
      • Orange, California, United States, 92868
        • Recruiting
        • UC Irvine Manchester Pavilion
        • Contact:
          • UCI Chao Family Comprehensive Cancer Center
          • Phone Number: 877-827-8839
          • Email: ucstudy@uci.edu
      • San Francisco, California, United States, 94143
        • Recruiting
        • UCSF
        • Contact:
    • Colorado
      • Denver, Colorado, United States, 80218
      • Denver, Colorado, United States, 80218
    • Connecticut
      • New Haven, Connecticut, United States, 06510
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic
      • Lake Mary, Florida, United States, 32746
      • Pembroke Pines, Florida, United States, 33028
        • Recruiting
        • Memorial Cancer Institute
      • Sarasota, Florida, United States, 34232
        • Recruiting
        • Florida Cancer Specialists
        • Contact:
    • Indiana
      • Fort Wayne, Indiana, United States, 46804
        • Recruiting
        • Fort Wayne Medical Oncology and Hematology
    • Kentucky
      • Louisville, Kentucky, United States, 40241
    • Louisiana
      • Jefferson, Louisiana, United States, 70121
    • Maryland
      • Columbia, Maryland, United States, 21044
    • Michigan
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
      • Minneapolis, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
    • Ohio
      • Canton, Ohio, United States, 44718
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
    • Oregon
    • Tennessee
    • Texas
      • Austin, Texas, United States, 78705
      • Dallas, Texas, United States, 75230
      • Dallas, Texas, United States, 75246
      • Fort Worth, Texas, United States, 76104
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas, MD Anderson
        • Contact:
      • San Antonio, Texas, United States, 78217
      • Tyler, Texas, United States, 75702
    • Virginia
      • Fairfax, Virginia, United States, 22031
      • Fairfax, Virginia, United States, 22031
      • Norfolk, Virginia, United States, 23502
    • Washington
      • Seattle, Washington, United States, 98109

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:

  • Age ≥ 18 years at time of signing ICF
  • ECOG Performance Status of 0 or 1
  • Histologic documentation of incurable, locally advanced or metastatic tumor of the type being evaluated in individual cohorts.
  • Adequate hepatic and renal function and adequate bone marrow reserve function.
  • For combination cohorts, participants must be eligible to receive the chemotherapy or targeted agent.
  • Ph1a only: No more than three prior therapeutic regimens.
  • Ph1b only: Must be FOLFIRI naïve participants and must have received only 1 prior therapeutic regimen administered for the treatment of cancer in the advanced/metastatic setting - OR - FOLFIRI naïve participants that only received adjuvant therapy who progressed within six months after completing adjuvant therapy, and are confirmed to have locally advanced/metastatic disease

Key Exclusion Criteria:

  • Inability to comply with study and follow-up procedures.
  • Prior DR5 agonist therapy.
  • Concomitant use of agents well-known to cause liver toxicity.
  • Concomitant use of anti-cancer agents
  • Palliative radiation to bone metastases within 2 weeks prior to Day 1.
  • Major surgical procedure within 4 weeks prior to Day 1.
  • Untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Participants with a history of treated CNS metastases are eligible.
  • Prior use of any chemotherapeutic agent or small molecule inhibitors (SMI) within 2 weeks or 5 half-lives, prior to the first dose of study treatment
  • Treatment with a monoclonal antibody, or any other anticancer agent (including biologic, experimental, or hormonal therapy) investigational or otherwise, that is not chemotherapy or a SMI, within 4 weeks or five half-lives prior to first dose of study treatment.
  • Ph1b: Participants who have previously received FOLFIRI treatment in the adjuvant, advanced, or metastatic disease setting

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: Ph1b: FOLFIRI + Bevacizumab
Standard of Care FOLFIRI + bevacizumab will be administered intravenously
Drug: FOLFIRI
Chemotherapy Regimen
Other Names:
  • Leucovorin
  • Irinotecan
  • Fluorouracil or 5-FU
Drug: Bevacizumab (and approved biosimilars)
Targeted Therapy
Other Names:
  • Avastin
Experimental: Ph1a: Aplitabart Single Agent Alternate Dosing Escalation
Aplitabart will be administered intravenously as a single agent on an alternate dosing schedule.
Drug: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug
Experimental: Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion
Aplitabart will be administered intravenously in combination with FOLFIRI± bevacizumab.
Drug: FOLFIRI
Chemotherapy Regimen
Other Names:
  • Leucovorin
  • Irinotecan
  • Fluorouracil or 5-FU
Drug: Bevacizumab (and approved biosimilars)
Targeted Therapy
Other Names:
  • Avastin
Drug: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug
Experimental: Ph1a: Aplitabart + Birinapant Escalation and Expansion
Aplitabart will be administered intravenously in combination with Birinapant which will also be administered intravenously.
Drug: Birinapant
SMAC-mimetic Investigational Drug
Drug: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug
Experimental: Ph1a: Aplitabart + Venetoclax Escalation and Expansion
Aplitabart will be administered intravenously in combination with Venetoclax.
Drug: Venetoclax
Targeted Therapy
Other Names:
  • Venclexta
Drug: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug
Experimental: Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion
Aplitabart will be administered intravenously in combination with Docetaxel and Gemcitabine.
Drug: Gemcitabine
Chemotherapy
Other Names:
  • Gemzar
Drug: Docetaxel
Chemotherapy
Other Names:
  • Taxotere
  • Docefrez
Drug: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug
Experimental: Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion
Aplitabart will be administered intravenously in combination with Venetoclax and Azacitidine.
Drug: Azacitidine
Chemotherapy
Other Names:
  • VIDAZA
Drug: Venetoclax
Targeted Therapy
Other Names:
  • Venclexta
Drug: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug
Experimental: Ph1b: Aplitabart + FOLFIRI + Bevacizumab
Aplitabart will be administered intravenously in combination with FOLFIRI + bevacizumab
Drug: FOLFIRI
Chemotherapy Regimen
Other Names:
  • Leucovorin
  • Irinotecan
  • Fluorouracil or 5-FU
Drug: Bevacizumab (and approved biosimilars)
Targeted Therapy
Other Names:
  • Avastin
Drug: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ph1b: Progression-Free Survival (PFS)
Time Frame: Study duration of approximately 36 months
PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 by investigator or death, whichever occurs first.
Study duration of approximately 36 months
Ph1a: Adverse Events of aplitabart as single agent and with FOLFIRI ± bevacizumab, aplitibart with birinapant, aplitibart with venetoclax, aplitibart with venetoclax and azacitadine, and aplitibart with gemcitabine and docetaxel
Time Frame: From Cycle 1 Day 1 through 28 days after the final dose of study drug
Incidence of treatment-related AEs graded according to the NCI Common Technology Criteria for Adverse Events (CTCAE) v5.0
From Cycle 1 Day 1 through 28 days after the final dose of study drug
Ph1a: To identify the recommended expansion dose for aplitabart as single agent, with FOLFIRI ± bevacizumab, aplitibart with birinapant, aplitibart with venetoclax, aplitibart with venetoclax and azacitadine, and aplitibart with gemcitabine and docetaxel
Time Frame: 4 weeks
Relationship between aplitabart dose and safety, PK, activity, and endpoints.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ph1a and Ph1b: Duration of Response (DoR)
Time Frame: Study duration of approximately 36 months
Preliminary efficacy of duration of response (DoR)
Study duration of approximately 36 months
Ph1a and Ph1b: Overall Survival (OS)
Time Frame: Study duration of approximately 36 months
OS is defined as the time from first dose (Ph1a) or randomization (Ph1b) to death due to any cause
Study duration of approximately 36 months
Ph1a and Ph1b: Objective Response Rate (ORR)
Time Frame: Study duration of approximately 36 months
Preliminary efficacy of objective response rate (ORR)
Study duration of approximately 36 months
Ph1a: Progression-Free Survival (PFS)
Time Frame: Study duration of approximately 36 months
PFS is defined as the time from first dose (Ph1a) to the first documented disease progression per RECIST 1.1 by investigator or death, whichever occurs first.
Study duration of approximately 36 months
Ph1a and Ph1b: Area Under the Curve (AUC) of aplitabart
Time Frame: At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Area Under the Curve (AUC) of aplitabart as a single agent and in combination with the anticancer agents listed above.
At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Ph1a and Ph1b: Clearance (CL) of aplitabart
Time Frame: At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Clearance (CL) of aplitabart as a single agent and in combination with the anticancer agents listed above.
At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Ph1a and Ph1b: Volume of distribution (V) of aplitabart
Time Frame: At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Volume of distribution (V) of aplitabart as a single agent and in combination with the anticancer agents listed above.
At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Ph1a and Ph1b: Maximum Concentration (c-max) of aplitabart
Time Frame: At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Maximum Concentration of aplitabart as a single agent and in combination with the anticancer agents listed above.
At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Ph1a and Ph1b: Immunogenicity
Time Frame: through end of treatment at approximately 6 months
Immunogenicity as assessed by detection of anti-drug antibodies (ADAs) to aplitabart
through end of treatment at approximately 6 months
Ph1b: Adverse events of aplitabart + FOLFIRI + bevacizumab
Time Frame: From Cycle 1 Day 1 through 28 days after the final dose of study drug
Incidence of treatment-related AEs graded according to the NCI Common Technology Criteria for Adverse Events (CTCAE) v5.0
From Cycle 1 Day 1 through 28 days after the final dose of study drug

Collaborators and Investigators

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

Sponsor

IGM Biosciences, Inc.

Investigators

  • Study Director: Eric Humke, MD, PhD, IGM Biosciences

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 23, 2020

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

August 1, 2027

Study Registration Dates

First Submitted

September 4, 2020

First Submitted That Met QC Criteria

September 11, 2020

First Posted (Actual)

September 17, 2020

Study Record Updates

Last Update Posted (Actual)

April 16, 2024

Last Update Submitted That Met QC Criteria

April 12, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IGM-8444-001

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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