A Study to Evaluate Immunotherapy Combinations in Participants With Gastrointestinal Malignancies

NCT03720678 | Completed Phase 1 FDA Drug

• 1 other identifier: ARC-3 (AB928CSP0003)
• Study Type: interventional
• Target: 44
• Locations: 2 countries
• Sites: 24

Brief Summary

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).

Conditions

GastroEsophageal Cancer; Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events (AEs)

  From first dose date to 90 days after the last dose (Approximately 1 year)

• Incidence of dose-limiting toxicities (DLTs) during dose escalation phase

  From first dose date to 28 days after the first dose

Secondary Outcomes (8)

• Plasma concentration of etrumadenant

  Recorded at baseline (prior to first dose), during the first 4 cycles of treatment (2 months), at end of treatment and 30 days post end of treatment (i.e. in total approximately 3 months)

• Percentage of participants with Objective Response as determined by Investigator according to RECIST v1.1

  From study enrolment until participation discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 3-5 years)

• Percentage of participants with Disease Control (complete response, partial response, or stable disease) for > 6 months as determined by RECIST v1.1

  From study enrolment until disease progression or loss of clinical benefit (up to approximately 3-5 years)

• Duration of Response as determined by the Investigator according to RECIST v1.1

  From the date of first occurrence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years)

• Progression Free Survival (PFS) as determined by the Investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  From start of treatment up to first occurrence of progressive disease or death from any cause, whichever occurs first (up to approximately 3-5 years)

Study Arms (3)

Dose Escalation

EXPERIMENTAL

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.

Drug: etrumadenant; Drug: mFOLFOX

Dose Expansion-GE

EXPERIMENTAL

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

Drug: etrumadenant; Drug: mFOLFOX

Dose Expansion-CRC

EXPERIMENTAL

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

Drug: etrumadenant; Drug: mFOLFOX

Interventions

etrumadenant DRUG

Etrumadenant is an A2aR and A2bR antagonist.

Also known as: AB928

Dose Escalation; Dose Expansion-CRC; Dose Expansion-GE

mFOLFOX DRUG

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

Dose Escalation; Dose Expansion-CRC; Dose Expansion-GE

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Arcus Biosciences, Inc.: lead

Study Sites (24)

Arizona Clinical Research Center

Tucson, Arizona, 85715, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Maryland Oncology Hematology

Rockville, Maryland, 20850, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

QUEST Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 16148, United States

Location

Prisma Health

Greenville, South Carolina, 29605, United States

Location

Texas Oncology - Austin Midtown

Austin, Texas, 78705, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Texas Oncology - Fort Worth Cancer Center

Fort Worth, Texas, 76104, United States

Location

Texas Oncology - San Antonio Northeast

San Antonio, Texas, 78217, United States

Location

Texas Oncology - San Antonio Medical Center

San Antonio, Texas, 78240, United States

Location

Texas Oncology - Tyler

Tyler, Texas, 75702, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Border Medical Oncology

Albury, New South Wales, 2640, Australia

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

The Kinghorn Cancer Centre

Darlinghurst, New South Wales, 2010, Australia

Location

St. George Private Hospital

Kogarah, New South Wales, 2217, Australia

Location

Macquarie University Hospital

Macquarie Park, New South Wales, 2109, Australia

Location

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, 3199, Australia

Location

Cabrini Hospital

Malvern, Victoria, 3144, Australia

Location

Related Links

• ARC-3 - Lay Summary (English Version)

MeSH Terms

Conditions

Colorectal Neoplasms

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

Study Officials

• Medical Director

  Arcus Biosciences, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+3 dose escalation

Study Record Dates

• First Submitted: October 24, 2018
• First Posted: October 25, 2018
• Study Start: November 18, 2018
• Primary Completion: January 27, 2021
• Study Completion: June 25, 2021
• Last Updated: May 24, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

AU (7); US (17)