A Study to Evaluate Immunotherapy Combinations in Participants With Gastrointestinal Malignancies

NCT ID: NCT03720678

Last Updated: 2024-05-24

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

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-18

Study Completion Date

2021-06-25

Brief Summary

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This is a Phase 1/1b, open-label, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical activity of etrumadenant (AB928) in combination with mFOLFOX in participants with advanced metastatic gastroesophageal Cancer (GEC) or colorectal cancer (CRC).

Detailed Description

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In the dose escalation phase, escalating doses of etrumadenant in combination with mFOLFOX at standard doses will be assessed in participants with advanced metastatic GEC or CRC. Eligible participants will receive oral administration of etrumadenant as well as IV infusion of mFOLFOX. The recommended dose for expansion (RDE) of etrumadenant will be determined upon completion of the dose-escalation phase.

In the dose expansion phase, etrumadenant at the RDE in combination with mFOLFOX at standard doses may be assessed in participants with advanced metastatic GEC or CRC.

Overall duration of treatment will depend on how well the treatment is tolerated. Treatment may continue until unacceptable toxicity or progressive disease or other reasons specified in the protocol.

Conditions

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GastroEsophageal Cancer Colorectal Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

3+3 dose escalation
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation

Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The RDE of etrumadenant will be determined in this part with escalating doses of etrumadenant in combination with the standard mFOLFOX chemotherapy regimen in participants with gastroesophageal or colorectal cancer.

Group Type EXPERIMENTAL

etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist.

mFOLFOX

Intervention Type DRUG

Oxaliplatin, Leucovorin and 5-fluorouracil given as part of standard mFOLFOX chemotherapy regimen

Dose Expansion-GE

The RDE of etrumadenant will be determined from the dose escalation part. Etrumadenant will be given in combination with the standard mFOLFOX chemotherapy regimen in participants with gastroesophageal cancer

Group Type EXPERIMENTAL

etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist.

mFOLFOX

Intervention Type DRUG

Oxaliplatin, Leucovorin and 5-fluorouracil given as part of standard mFOLFOX chemotherapy regimen

Dose Expansion-CRC

The RDE of etrumadenant will be determined from the dose escalation part. Etrumadenant will be given in combination with the standard mFOLFOX chemotherapy regimen in participants with colorectal cancer

Group Type EXPERIMENTAL

etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist.

mFOLFOX

Intervention Type DRUG

Oxaliplatin, Leucovorin and 5-fluorouracil given as part of standard mFOLFOX chemotherapy regimen

Interventions

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etrumadenant

Etrumadenant is an A2aR and A2bR antagonist.

Intervention Type DRUG

mFOLFOX

Oxaliplatin, Leucovorin and 5-fluorouracil given as part of standard mFOLFOX chemotherapy regimen

Intervention Type DRUG

Other Intervention Names

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AB928

Eligibility Criteria

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Inclusion Criteria

* Male or female participants ≥ 18 years
* Histologically confirmed gastroesophageal cancer or colorectal cancer that is metastatic, advanced or recurrent with progression
* Participants for whom mFOLFOX is considered appropriate therapy
* Must have at least 1 measurable lesion per RECIST v1.1.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
* Must have received standard of care, including potentially curative available therapies or interventions.
* Confirm that an archival tissue sample is available and ≤ 24 months old; if not, a new biopsy of a tumor lesion must be obtained.
* Adequate organ and marrow function
* Previously treated central nervous system metastases, meeting the following criteria:

* No evidence of progression by magnetic resonance imaging for at least 4 weeks prior to first dose.
* Neurologic symptoms returned to baseline.
* No immunosuppressive doses of systemic corticosteroids for at least 2 weeks before investigational product administration.
* No carcinomatous meningitis.

Exclusion Criteria

* Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of investigational product.
* Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of investigational product hazardous (eg interstitial lung disease, active infections requiring antibiotics, recent hospitalization with unresolved symptoms) or obscure the interpretation of toxicity determination or AEs, or concurrent medical condition requiring the use of immunosuppressive medications or immunosuppressive doses of systemic or absorbable topical corticosteroids.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 30 days after the last dose of etrumadenant in combination with mFOLFOX.
* Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy.

* Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
* Participants with asthma who require intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections will not be excluded from this study. Participants on chronic systemic corticosteroids will be excluded from the study.
* Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, breast, or prostate.
* Prior chemotherapy, targeted small-molecule therapy, or radiation therapy within 4 weeks prior to Day 1 or has not recovered (ie, ≥ Grade 1 or baseline) from AEs due to a previously administered agent, except ≤ Grade 2 alopecia or ≤ Grade 2 neuropathy and other AEs ≤ Grade 2 considered not clinically significant by the Medical Monitor and Investigator.
* Use of other investigational drugs (drugs not marketed for any indication) within 28 days of investigational product administration.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Arcus Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Arcus Biosciences, Inc.

Locations

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Arizona Clinical Research Center

Tucson, Arizona, United States

Site Status

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Site Status

Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Maryland Oncology Hematology

Rockville, Maryland, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

QUEST Research Institute

Farmington Hills, Michigan, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

Carolina BioOncology Institute

Huntersville, North Carolina, United States

Site Status

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Prisma Health

Greenville, South Carolina, United States

Site Status

Texas Oncology - Austin Midtown

Austin, Texas, United States

Site Status

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Site Status

Texas Oncology - Fort Worth Cancer Center

Fort Worth, Texas, United States

Site Status

Texas Oncology - San Antonio Northeast

San Antonio, Texas, United States

Site Status

Texas Oncology - San Antonio Medical Center

San Antonio, Texas, United States

Site Status

Texas Oncology - Tyler

Tyler, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Border Medical Oncology

Albury, New South Wales, Australia

Site Status

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Site Status

The Kinghorn Cancer Centre

Darlinghurst, New South Wales, Australia

Site Status

St. George Private Hospital

Kogarah, New South Wales, Australia

Site Status

Macquarie University Hospital

Macquarie Park, New South Wales, Australia

Site Status

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, Australia

Site Status

Cabrini Hospital

Malvern, Victoria, Australia

Site Status

Countries

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United States Australia

Related Links

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https://trials.arcusbio.com/study/?id=ARC-3

ARC-3 - Lay Summary (English Version)

Other Identifiers

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ARC-3 (AB928CSP0003)

Identifier Type: -

Identifier Source: org_study_id

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