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

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: Terminated
• Conditions: Sarcoma; Acute Myeloid Leukemia; Colorectal Cancer; Solid Tumor; Chronic Lymphocytic Leukemia; Non Hodgkin Lymphoma; Chondrosarcoma; Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: Gemcitabine; Drug: Azacitidine; Drug: FOLFIRI; Drug: Bevacizumab (and approved biosimilars); Drug: Birinapant; Drug: Venetoclax; Drug: Docetaxel; Drug: Aplitabart (IGM-8444)

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 (Actual): 272
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Kingswood, Australia, 2747
    • Napean Cancer Care
  • Southport, Australia, QLD 4215
    • Tasman Health
  • Woodville South, Australia, 5011
    • Queen Elizabeth Hospital
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead
    • Wollongong, New South Wales, Australia, 2500
      • Southern Medical Day Care Centre
  • Victoria
    • Melbourne, Victoria, Australia, 3052
      • Peter MacCallum Cancer Centre
• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Dijon, France, 21000
    • Centre Georges Francois Leclerc
  • Paris, France, 75010
    • Saint Louis Hospital
  • Saint-Herblain, France, 44800
    • Institut de cancerologie de l'ouest
  • Villejuif, France, 94805
    • Gustave Roussy
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03080
    • Asan Medical Center
  • Soeul, Korea, Republic of
    • Severance Hospital - Yonsei Cancer Center
  • Gangnam-gu
    • Seoul, Gangnam-gu, Korea, Republic of, 06351
      • Samsung Medical Center
  • Seongnam-si
    • Gyeonggi-do, Seongnam-si, Korea, Republic of, 13620
      • Gachon University Gil Hospital
    • Gyeonggi-do, Seongnam-si, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
• Spain
  • Barcelona, Spain, 08035
    • Vall d'Hebron Institut d'Oncologia
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra
  • Madrid, Spain, 28040
    • Madrid FJD
  • Madrid, Spain, 28050
    • Madrid CIOCC - HM Universitario Sanchinnarro
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Los Alamitos, California, United States, 90720
      • Cancer and Blood Specialty Clinic (CBSC)
    • Los Angeles, California, United States, 90404
      • UCLA
    • Los Angeles, California, United States, 90033
      • USC Norris
    • Orange, California, United States, 92868
      • UC Irvine Manchester Pavilion
    • San Francisco, California, United States, 94143
      • UCSF
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers
    • Denver, Colorado, United States, 80218
      • SCRI at HealthOne
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Lake Mary, Florida, United States, 32746
      • FL Cancer Specialists - Lake Mary
    • Pembroke Pines, Florida, United States, 33028
      • Memorial Cancer Institute
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology and Hematology
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • Norton Cancer Institute
  • Louisiana
    • Jefferson, Louisiana, United States, 70121
      • Ochsner Cancer
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology, PA - Columbia
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Start Midwest
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology - Minneapolis Clinic
    • Minneapolis, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI - Tennessee
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology - Austin
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
    • Dallas, Texas, United States, 75246
      • US Oncology - Dallas
    • Fort Worth, Texas, United States, 76104
      • US Oncology- Texas Oncology - Fort Worth
    • Houston, Texas, United States, 77030
      • The University of Texas, MD Anderson
    • San Antonio, Texas, United States, 78217
      • Texas Oncology - San Antonio Northeast
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
    • Norfolk, Virginia, United States, 23502
      • US Oncology- Virginia Oncology - Norfolk
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Alliance - Fred Hutch

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

8

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)	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	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	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)	Preliminary efficacy of duration of response (DoR)	Study duration of approximately 36 months
Ph1a and Ph1b: Overall Survival (OS)	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)	Preliminary efficacy of objective response rate (ORR)	Study duration of approximately 36 months
Ph1a: Progression-Free Survival (PFS)	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	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	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	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	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	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	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

• Sponsor: IGM Biosciences, Inc.
• Investigators: Study Director: Eric Humke, MD, PhD, IGM Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2020
• Primary Completion (Actual): January 20, 2025
• Study Completion (Actual): January 20, 2025

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): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Metastatic Cancer; Newly diagnosed; Relapsed and/or Refractory; Advanced Tumors; Hematological cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Sarcoma; Neoplasms, Connective and Soft Tissue; Leukemia, Lymphoid; Neoplasms, Connective Tissue; Leukemia; Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Chondrosarcoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Micronutrients; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Protective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antidotes; Vitamin B Complex; Vitamins; Docetaxel; Bevacizumab; Irinotecan; Gemcitabine; Venetoclax; Fluorouracil; Azacitidine; Leucovorin
• Other Study ID Numbers: IGM-8444-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No