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

NCT04553692 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: IGM-8444-001
• Study Type: interventional
• Target: 272
• Locations: 5 countries
• Sites: 58

Brief Summary

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.

Conditions

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

Keywords

Relapsed and/or Refractory; Metastatic Cancer; Advanced Tumors; Hematological cancer; Newly diagnosed

Outcome Measures

Primary Outcomes (3)

• 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

• 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

Secondary Outcomes (10)

• Ph1a and Ph1b: Area Under the Curve (AUC) of aplitabart

  At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months

• Ph1a and Ph1b: Clearance (CL) of aplitabart

  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

  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

  At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months

• Ph1a and Ph1b: Immunogenicity

  through end of treatment at approximately 6 months

Study Arms (8)

Ph1a: Aplitabart Single Agent Alternate Dosing Escalation

EXPERIMENTAL

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

Drug: Aplitabart (IGM-8444)

Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion

EXPERIMENTAL

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

Drug: Aplitabart (IGM-8444); Drug: FOLFIRI; Drug: Bevacizumab (and approved biosimilars)

Ph1a: Aplitabart + Birinapant Escalation and Expansion

EXPERIMENTAL

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

Drug: Aplitabart (IGM-8444); Drug: Birinapant

Ph1a: Aplitabart + Venetoclax Escalation and Expansion

EXPERIMENTAL

Aplitabart will be administered intravenously in combination with Venetoclax.

Drug: Aplitabart (IGM-8444); Drug: Venetoclax

Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion

EXPERIMENTAL

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

Drug: Aplitabart (IGM-8444); Drug: Gemcitabine; Drug: Docetaxel

Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion

EXPERIMENTAL

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

Drug: Aplitabart (IGM-8444); Drug: Venetoclax; Drug: Azacitidine

Ph1b: Aplitabart + FOLFIRI + Bevacizumab

EXPERIMENTAL

Aplitabart will be administered intravenously in combination with FOLFIRI + bevacizumab

Drug: Aplitabart (IGM-8444); Drug: FOLFIRI; Drug: Bevacizumab (and approved biosimilars)

Ph1b: FOLFIRI + Bevacizumab

EXPERIMENTAL

Standard of Care FOLFIRI + bevacizumab will be administered intravenously

Drug: FOLFIRI; Drug: Bevacizumab (and approved biosimilars)

Interventions

Aplitabart (IGM-8444) DRUG

DR5 Agonist Investigational Drug

Ph1a: Aplitabart + Birinapant Escalation and Expansion; Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion; Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion; Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion; Ph1a: Aplitabart + Venetoclax Escalation and Expansion; Ph1a: Aplitabart Single Agent Alternate Dosing Escalation; Ph1b: Aplitabart + FOLFIRI + Bevacizumab

FOLFIRI DRUG

Chemotherapy Regimen

Also known as: Fluorouracil or 5-FU, Leucovorin, Irinotecan

Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion; Ph1b: Aplitabart + FOLFIRI + Bevacizumab; Ph1b: FOLFIRI + Bevacizumab

Bevacizumab (and approved biosimilars) DRUG

Targeted Therapy

Also known as: Avastin

Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion; Ph1b: Aplitabart + FOLFIRI + Bevacizumab; Ph1b: FOLFIRI + Bevacizumab

Birinapant DRUG

SMAC-mimetic Investigational Drug

Ph1a: Aplitabart + Birinapant Escalation and Expansion

Venetoclax DRUG

Targeted Therapy

Also known as: Venclexta

Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion; Ph1a: Aplitabart + Venetoclax Escalation and Expansion

Gemcitabine DRUG

Chemotherapy

Also known as: Gemzar

Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion

Docetaxel DRUG

Chemotherapy

Also known as: Taxotere, Docefrez

Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion

Azacitidine DRUG

Chemotherapy

Also known as: VIDAZA

Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• IGM Biosciences, Inc.: lead

Study Sites (58)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Cancer and Blood Specialty Clinic (CBSC)

Los Alamitos, California, 90720, United States

Location

USC Norris

Los Angeles, California, 90033, United States

Location

UCLA

Los Angeles, California, 90404, United States

Location

UC Irvine Manchester Pavilion

Orange, California, 92868, United States

Location

UCSF

San Francisco, California, 94143, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

SCRI at Healthone

Denver, Colorado, 80218, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

FL Cancer Specialists - Lake Mary

Lake Mary, Florida, 32746, United States

Location

Memorial Cancer Institute

Pembroke Pines, Florida, 33028, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, 46804, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40241, United States

Location

Ochsner Cancer

Jefferson, Louisiana, 70121, United States

Location

Maryland Oncology Hematology, PA - Columbia

Columbia, Maryland, 21044, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Minnesota Oncology - Minneapolis Clinic

Minneapolis, Minnesota, 55404, United States

Location

Mayo Clinic

Minneapolis, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Gabrail Cancer Research

Canton, Ohio, 44718, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

SCRI - Tennessee

Nashville, Tennessee, 37203, United States

Location

Texas Oncology - Austin

Austin, Texas, 78705, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

US Oncology - Dallas

Dallas, Texas, 75246, United States

Location

US Oncology- Texas Oncology - Fort Worth

Fort Worth, Texas, 76104, United States

Location

The University of Texas, MD Anderson

Houston, Texas, 77030, United States

Location

Texas Oncology - San Antonio Northeast

San Antonio, Texas, 78217, United States

Location

Texas Oncology - Tyler

Tyler, Texas, 75702, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

US Oncology- Virginia Oncology - Norfolk

Norfolk, Virginia, 23502, United States

Location

Seattle Cancer Alliance - Fred Hutch

Seattle, Washington, 98109, United States

Location

Westmead

Westmead, New South Wales, 2145, Australia

Location

Southern Medical Day Care Centre

Wollongong, New South Wales, 2500, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3052, Australia

Location

Napean Cancer Care

Kingswood, 2747, Australia

Location

Tasman Health

Southport, QLD 4215, Australia

Location

Queen Elizabeth Hospital

Woodville South, 5011, Australia

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Centre Georges Francois Leclerc

Dijon, 21000, France

Location

Saint Louis Hospital

Paris, 75010, France

Location

Institut de Cancérologie de l'Ouest

Saint-Herblain, 44800, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Samsung Medical Center

Seoul, Gangnam-gu, 06351, South Korea

Location

Gachon University Gil Hospital

Gyeonggi-do, Seongnam-si, 13620, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, Seongnam-si, 13620, South Korea

Location

Asan Medical Center

Seoul, 03080, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital - Yonsei Cancer Center

Soeul, South Korea

Location

Vall d'Hebron Institut d'Oncologia

Barcelona, 08035, Spain

Location

Clinica Universidad de Navarra

Madrid, 28027, Spain

Location

Madrid FJD

Madrid, 28040, Spain

Location

Madrid CIOCC - HM Universitario Sanchinnarro

Madrid, 28050, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Lymphoma, Non-Hodgkin; Sarcoma; Chondrosarcoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Acute; Neoplasm Metastasis

Interventions

IFL protocol; Fluorouracil; Leucovorin; Irinotecan; Bevacizumab; birinapant; venetoclax; Gemcitabine; Docetaxel; Azacitidine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Aza Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Eric Humke, MD, PhD

  IGM Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Phase 1a is non-randomized; Ph1b is randomized
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2020
• First Posted: September 17, 2020
• Study Start: September 23, 2020
• Primary Completion: January 20, 2025
• Study Completion: January 20, 2025
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4); US (37); AU (6); FR (5); KR (6)