We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase I Study of IGM-8444 Alone and in Combination in Subjects With Relapsed, Refractory, or Newly Diagnosed Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04553692
Recruitment Status : Recruiting
First Posted : September 17, 2020
Last Update Posted : September 27, 2022
Sponsor:
Information provided by (Responsible Party):
IGM Biosciences, Inc.

Brief Summary:
This study is a first-in-human, Phase 1, multicenter, open-label study to determine the safety, tolerability and pharmacokinetics of IGM-8444 as a single agent and in combination in subjects with relapsed and/or refractory solid or hematologic cancers, as well as newly diagnosed cancers

Condition or disease Intervention/treatment Phase
Solid Tumor Colorectal Cancer Non Hodgkin Lymphoma Sarcoma Chondrosarcoma Small Lymphocytic Lymphoma Chronic Lymphocytic Leukemia Acute Myeloid Leukemia Drug: IGM-8444 Drug: FOLFIRI Drug: Bevacizumab (and approved biosimilars) Drug: Birinapant Drug: Venetoclax Drug: Gemcitabine Drug: Docetaxel Drug: Azacitidine Phase 1

Detailed Description:

Patients will be enrolled in two stages: a dose-escalation stage and an expansion stage. IGM-8444 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.

IGM-8444 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).

IGM-8444 will be administered intravenously (IV).

An alternative dosing schedule may be evaluated.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multicenter, Phase I Study of IGM-8444 as a Single Agent and in Combination in Subjects With Relapsed, Refractory, or Newly Diagnosed Cancers
Actual Study Start Date : September 23, 2020
Estimated Primary Completion Date : August 2025
Estimated Study Completion Date : October 2025


Arm Intervention/treatment
Experimental: IGM-8444 Single Agent Alternate Dosing Escalation
IGM-8444 will be administered intravenously as a single agent on an alternate dosing schedule.
Drug: IGM-8444
DR5 Agonist Investigational Drug

Experimental: IGM-8444 Single Agent Expansion
IGM-8444 will be administered intravenously as a single agent in disease specific cohorts.
Drug: IGM-8444
DR5 Agonist Investigational Drug

Experimental: IGM-8444 + FOLFIRI ± bevacizumab Escalation and Expansion
IGM-8444 will be administered intravenously in combination with FOLFIRI.
Drug: IGM-8444
DR5 Agonist Investigational Drug

Drug: FOLFIRI
Chemotherapy Regimen
Other Names:
  • Fluorouracil or 5-FU
  • Leucovorin
  • Irinotecan

Drug: Bevacizumab (and approved biosimilars)
Targeted Therapy
Other Name: Avastin

Experimental: IGM-8444 + Birinapant Escalation and Expansion
IGM-8444 will be administered intravenously in combination with Birinapant which will also be administered intravenously.
Drug: IGM-8444
DR5 Agonist Investigational Drug

Drug: Birinapant
SMAC-mimetic Investigational Drug

Experimental: IGM-8444 + Venetoclax Escalation and Expansion
IGM-8444 will be administered intravenously in combination with Venetoclax.
Drug: IGM-8444
DR5 Agonist Investigational Drug

Drug: Venetoclax
Targeted Therapy
Other Name: Venclexta

Experimental: IGM-8444 + Docetaxel + Gemcitabine Escalation and Expansion
IGM-8444 will be administered intravenously in combination with Docetaxel and Gemcitabine.
Drug: IGM-8444
DR5 Agonist Investigational Drug

Drug: Gemcitabine
Chemotherapy
Other Name: Gemzar

Drug: Docetaxel
Chemotherapy
Other Names:
  • Taxotere
  • Docefrez

Experimental: IGM-8444 + Venetoclax + Azacitidine Escalation and Expansion
IGM-8444 will be administered intravenously in combination with Venetoclax and Azacitidine.
Drug: IGM-8444
DR5 Agonist Investigational Drug

Drug: Venetoclax
Targeted Therapy
Other Name: Venclexta

Drug: Azacitidine
Chemotherapy
Other Name: VIDAZA




Primary Outcome Measures :
  1. Adverse Events of IGM-8444 as single agent and with FOLFIRI ± bevacizumab, IGM-8444 with birinapant, IGM-8444 with venetoclax, IGM-8444 with venetoclax and azacitadine, and IGM-8444 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

  2. To identify the recommended expansion dose for IGM-8444 as single agent, with FOLFIRI ± bevacizumab, IGM-8444 with birinapant, IGM-8444 with venetoclax, IGM-8444 with venetoclax and azacitadine, and IGM-8444 with gemcitabine and docetaxel [ Time Frame: 4 weeks ]
    Relationship between IGM-8444 dose and safety, PK, activity, and endpoints.


Secondary Outcome Measures :
  1. Area Under the Curve (AUC) of IGM-8444 [ 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 IGM-8444 as a single agent and in combination with the anticancer agents listed above.

  2. Clearance (CL) of IGM-8444 [ Time Frame: At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months ]
    Clearance (CL) of IGM-8444 as a single agent and in combination with the anticancer agents listed above.

  3. Volume of distribution (V) of IGM-8444 [ Time Frame: At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months ]
    Volume of distribution (V) of IGM-8444 as a single agent and in combination with the anticancer agents listed above.

  4. Immunogenicity [ Time Frame: through end of treatment at approximately 6 months ]
    Immunogenicity as assessed by detection of anti-drug antibodies (ADAs) to IGM-8444

  5. Objective Response Rate (ORR) [ Time Frame: Study duration of approximately 36 months ]
    Preliminary efficacy of objective response rate (ORR)

  6. Duration of Response (DoR) [ Time Frame: Study duration of approximately 36 months ]
    Preliminary efficacy of duration of response (DoR)

  7. Progression-Free Survival (PFS) [ Time Frame: Study duration of approximately 36 months ]
    Preliminary efficacy of progression-free survival (PFS)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Age ≥ 18 years at time of signing ICF
  • ECOG Performance Status of 0 or 1
  • 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.
  • 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, patients must be eligible to receive the chemotherapy or targeted agent.
  • No more than three prior therapeutic regimens

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). Patients with a history of treated CNS metastases are eligible.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04553692


Contacts
Layout table for location contacts
Contact: Clinical Trials 650 265 6428 clinicaltrials@igmbio.com

Locations
Layout table for location information
United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: Clinical Trials       clinicaltrials@igmbio.com   
United States, Colorado
SCRI at Healthone Recruiting
Denver, Colorado, United States, 80218
Contact: Clinical Trials       clinicaltrials@igmbio.com   
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06510
Contact: Clinical Trials       clinicaltrials@igmbio.com   
United States, Florida
Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: Clinical Trials       clinicaltrials@igmbio.com   
United States, Kentucky
Norton Cancer Institute Recruiting
Louisville, Kentucky, United States, 40241
Contact: Clinical Trials       clinicaltrials@igmbio.com   
United States, Oklahoma
Stephenson Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Clinical Trials       clinicaltrials@igmbio.com   
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Clinical Trials       clinicaltrials@igmbio.com   
United States, Tennessee
SCRI - Tennessee Recruiting
Nashville, Tennessee, United States, 37203
Contact: Clinical Trials       clinicaltrials@igmbio.com   
United States, Texas
Mary Crowley Cancer Research Recruiting
Dallas, Texas, United States, 75230
Contact: Clinical Trials       clinicaltrials@igmbio.com   
The University of Texas, MD Anderson Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Trials       clinicaltrials@igmbio.com   
Sponsors and Collaborators
IGM Biosciences, Inc.
Investigators
Layout table for investigator information
Study Director: Eric Humke, MD, PhD IGM Biosciences
Layout table for additonal information
Responsible Party: IGM Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT04553692    
Other Study ID Numbers: IGM-8444-001
First Posted: September 17, 2020    Key Record Dates
Last Update Posted: September 27, 2022
Last Verified: September 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by IGM Biosciences, Inc.:
Relapsed and/or Refractory
Metastatic Cancer
Advanced Tumors
Hematological cancer
Newly diagnosed
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Chondrosarcoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Sarcoma
Neoplasms, Connective and Soft Tissue
Leukemia, Lymphoid
Leukemia, B-Cell
Neoplasms, Connective Tissue
Leucovorin
Gemcitabine
Bevacizumab
Docetaxel
Fluorouracil
Irinotecan
Azacitidine
Venetoclax
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors