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

NCT ID: NCT04553692

Last Updated: 2025-03-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

272 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-23

Study Completion Date

2025-01-20

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Solid Tumor Colorectal Cancer Non Hodgkin Lymphoma Sarcoma Chondrosarcoma Small Lymphocytic Lymphoma Chronic Lymphocytic Leukemia Acute Myeloid Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Phase 1a is non-randomized; Ph1b is randomized

Study Groups

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Ph1a: Aplitabart Single Agent Alternate Dosing Escalation

Aplitabart will be administered intravenously as a single agent on an alternate dosing schedule.

Group Type EXPERIMENTAL

Aplitabart (IGM-8444)

Intervention Type DRUG

DR5 Agonist Investigational Drug

Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion

Aplitabart will be administered intravenously in combination with FOLFIRI± bevacizumab.

Group Type EXPERIMENTAL

Aplitabart (IGM-8444)

Intervention Type DRUG

DR5 Agonist Investigational Drug

FOLFIRI

Intervention Type DRUG

Chemotherapy Regimen

Bevacizumab (and approved biosimilars)

Intervention Type DRUG

Targeted Therapy

Ph1a: Aplitabart + Birinapant Escalation and Expansion

Aplitabart will be administered intravenously in combination with Birinapant which will also be administered intravenously.

Group Type EXPERIMENTAL

Aplitabart (IGM-8444)

Intervention Type DRUG

DR5 Agonist Investigational Drug

Birinapant

Intervention Type DRUG

SMAC-mimetic Investigational Drug

Ph1a: Aplitabart + Venetoclax Escalation and Expansion

Aplitabart will be administered intravenously in combination with Venetoclax.

Group Type EXPERIMENTAL

Aplitabart (IGM-8444)

Intervention Type DRUG

DR5 Agonist Investigational Drug

Venetoclax

Intervention Type DRUG

Targeted Therapy

Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion

Aplitabart will be administered intravenously in combination with Docetaxel and Gemcitabine.

Group Type EXPERIMENTAL

Aplitabart (IGM-8444)

Intervention Type DRUG

DR5 Agonist Investigational Drug

Gemcitabine

Intervention Type DRUG

Chemotherapy

Docetaxel

Intervention Type DRUG

Chemotherapy

Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion

Aplitabart will be administered intravenously in combination with Venetoclax and Azacitidine.

Group Type EXPERIMENTAL

Aplitabart (IGM-8444)

Intervention Type DRUG

DR5 Agonist Investigational Drug

Venetoclax

Intervention Type DRUG

Targeted Therapy

Azacitidine

Intervention Type DRUG

Chemotherapy

Ph1b: Aplitabart + FOLFIRI + Bevacizumab

Aplitabart will be administered intravenously in combination with FOLFIRI + bevacizumab

Group Type EXPERIMENTAL

Aplitabart (IGM-8444)

Intervention Type DRUG

DR5 Agonist Investigational Drug

FOLFIRI

Intervention Type DRUG

Chemotherapy Regimen

Bevacizumab (and approved biosimilars)

Intervention Type DRUG

Targeted Therapy

Ph1b: FOLFIRI + Bevacizumab

Standard of Care FOLFIRI + bevacizumab will be administered intravenously

Group Type EXPERIMENTAL

FOLFIRI

Intervention Type DRUG

Chemotherapy Regimen

Bevacizumab (and approved biosimilars)

Intervention Type DRUG

Targeted Therapy

Interventions

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Aplitabart (IGM-8444)

DR5 Agonist Investigational Drug

Intervention Type DRUG

FOLFIRI

Chemotherapy Regimen

Intervention Type DRUG

Bevacizumab (and approved biosimilars)

Targeted Therapy

Intervention Type DRUG

Birinapant

SMAC-mimetic Investigational Drug

Intervention Type DRUG

Venetoclax

Targeted Therapy

Intervention Type DRUG

Gemcitabine

Chemotherapy

Intervention Type DRUG

Docetaxel

Chemotherapy

Intervention Type DRUG

Azacitidine

Chemotherapy

Intervention Type DRUG

Other Intervention Names

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Fluorouracil or 5-FU Leucovorin Irinotecan Avastin Venclexta Gemzar Taxotere Docefrez VIDAZA

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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IGM Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eric Humke, MD, PhD

Role: STUDY_DIRECTOR

IGM Biosciences

Locations

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Mayo Clinic

Phoenix, Arizona, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Cancer and Blood Specialty Clinic (CBSC)

Los Alamitos, California, United States

Site Status

USC Norris

Los Angeles, California, United States

Site Status

UCLA

Los Angeles, California, United States

Site Status

UC Irvine Manchester Pavilion

Orange, California, United States

Site Status

UCSF

San Francisco, California, United States

Site Status

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Site Status

SCRI at Healthone

Denver, Colorado, United States

Site Status

Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

FL Cancer Specialists - Lake Mary

Lake Mary, Florida, United States

Site Status

Memorial Cancer Institute

Pembroke Pines, Florida, United States

Site Status

Florida Cancer Specialists

Sarasota, Florida, United States

Site Status

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, United States

Site Status

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status

Ochsner Cancer

Jefferson, Louisiana, United States

Site Status

Maryland Oncology Hematology, PA - Columbia

Columbia, Maryland, United States

Site Status

START Midwest

Grand Rapids, Michigan, United States

Site Status

Minnesota Oncology - Minneapolis Clinic

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Minneapolis, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Gabrail Cancer Research

Canton, Ohio, United States

Site Status

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

Providence Portland Medical Center

Portland, Oregon, United States

Site Status

SCRI - Tennessee

Nashville, Tennessee, United States

Site Status

Texas Oncology - Austin

Austin, Texas, United States

Site Status

Mary Crowley Cancer Research

Dallas, Texas, United States

Site Status

US Oncology - Dallas

Dallas, Texas, United States

Site Status

US Oncology- Texas Oncology - Fort Worth

Fort Worth, Texas, United States

Site Status

The University of Texas, MD Anderson

Houston, Texas, United States

Site Status

Texas Oncology - San Antonio Northeast

San Antonio, Texas, United States

Site Status

Texas Oncology - Tyler

Tyler, Texas, United States

Site Status

Inova Schar Cancer Institute

Fairfax, Virginia, United States

Site Status

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status

US Oncology- Virginia Oncology - Norfolk

Norfolk, Virginia, United States

Site Status

Seattle Cancer Alliance - Fred Hutch

Seattle, Washington, United States

Site Status

Westmead

Westmead, New South Wales, Australia

Site Status

Southern Medical Day Care Centre

Wollongong, New South Wales, Australia

Site Status

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status

Napean Cancer Care

Kingswood, , Australia

Site Status

Tasman Health

Southport, , Australia

Site Status

Queen Elizabeth Hospital

Woodville South, , Australia

Site Status

Institut Bergonié

Bordeaux, , France

Site Status

Centre Georges Francois Leclerc

Dijon, , France

Site Status

Saint Louis Hospital

Paris, , France

Site Status

Institut de Cancérologie de l'Ouest

Saint-Herblain, , France

Site Status

Gustave Roussy

Villejuif, , France

Site Status

Samsung Medical Center

Seoul, Gangnam-gu, South Korea

Site Status

Gachon University Gil Hospital

Gyeonggi-do, Seongnam-si, South Korea

Site Status

Seoul National University Bundang Hospital

Gyeonggi-do, Seongnam-si, South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital - Yonsei Cancer Center

Soeul, , South Korea

Site Status

Vall d'Hebron Institut d'Oncologia

Barcelona, , Spain

Site Status

Clinica Universidad de Navarra

Madrid, , Spain

Site Status

Madrid FJD

Madrid, , Spain

Site Status

Madrid CIOCC - HM Universitario Sanchinnarro

Madrid, , Spain

Site Status

Countries

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United States Australia France South Korea Spain

Other Identifiers

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IGM-8444-001

Identifier Type: -

Identifier Source: org_study_id

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