- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03720678
A Study to Evaluate Immunotherapy Combinations in Participants With Gastrointestinal Malignancies
A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Gastrointestinal Malignancies
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
New South Wales
-
Albury, New South Wales, Australia, 2640
- Border Medical Oncology
-
Camperdown, New South Wales, Australia, 2050
- Chris O'Brien Lifehouse
-
Darlinghurst, New South Wales, Australia, 2010
- The Kinghorn Cancer Centre
-
Kogarah, New South Wales, Australia, 2217
- St. George Private Hospital
-
Macquarie Park, New South Wales, Australia, 2109
- Macquarie University Hospital
-
-
Victoria
-
Frankston, Victoria, Australia, 3199
- Peninsula & South Eastern Haematology and Oncology Group
-
Malvern, Victoria, Australia, 3144
- Cabrini Hospital
-
-
-
-
Arizona
-
Tucson, Arizona, United States, 85715
- Arizona Clinical Research Center
-
-
Colorado
-
Denver, Colorado, United States, 80218
- Rocky Mountain Cancer Centers
-
-
Connecticut
-
New Haven, Connecticut, United States, 06520
- Yale Cancer Center
-
-
Maryland
-
Rockville, Maryland, United States, 20850
- Maryland Oncology Hematology
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Dana Farber Cancer Institute
-
-
Michigan
-
Farmington Hills, Michigan, United States, 48334
- Quest Research Institute
-
-
Nevada
-
Las Vegas, Nevada, United States, 89169
- Comprehensive Cancer Centers of Nevada
-
-
North Carolina
-
Huntersville, North Carolina, United States, 28078
- Carolina Biooncology Institute
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 16148
- UPMC Hillman Cancer Center
-
-
South Carolina
-
Greenville, South Carolina, United States, 29605
- Prisma Health
-
-
Texas
-
Austin, Texas, United States, 78705
- Texas Oncology - Austin Midtown
-
Dallas, Texas, United States, 75246
- Texas Oncology - Baylor Charles A. Sammons Cancer Center
-
Fort Worth, Texas, United States, 76104
- Texas Oncology - Fort Worth Cancer Center
-
San Antonio, Texas, United States, 78240
- Texas Oncology - San Antonio Medical Center
-
San Antonio, Texas, United States, 78217
- Texas Oncology - San Antonio Northeast
-
Tyler, Texas, United States, 75702
- Texas Oncology - Tyler
-
-
Virginia
-
Fairfax, Virginia, United States, 22031
- Virginia Cancer Specialists, PC
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Etrumadenant is an A2aR and A2bR antagonist.
Other Names:
Oxaliplatin, Leucovorin and 5-fluorouracil given as part of standard mFOLFOX chemotherapy regimen
|
Experimental: 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
|
Etrumadenant is an A2aR and A2bR antagonist.
Other Names:
Oxaliplatin, Leucovorin and 5-fluorouracil given as part of standard mFOLFOX chemotherapy regimen
|
Experimental: 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
|
Etrumadenant is an A2aR and A2bR antagonist.
Other Names:
Oxaliplatin, Leucovorin and 5-fluorouracil given as part of standard mFOLFOX chemotherapy regimen
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Incidence of Adverse Events (AEs)
Time Frame: From first dose date to 90 days after the last dose (Approximately 1 year)
|
From first dose date to 90 days after the last dose (Approximately 1 year)
|
Incidence of dose-limiting toxicities (DLTs) during dose escalation phase
Time Frame: From first dose date to 28 days after the first dose
|
From first dose date to 28 days after the first dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS) as determined by the Investigator according to RECIST v1.1
Time Frame: From start of treatment up to death from any cause (up to approximately 3-5 years)
|
From start of treatment up to death from any cause (up to approximately 3-5 years)
|
|
Plasma concentration of etrumadenant
Time Frame: 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)
|
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
Time Frame: From study enrolment until participation discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 3-5 years)
|
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
Time Frame: From study enrolment until disease progression or loss of clinical benefit (up to approximately 3-5 years)
|
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
Time Frame: 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)
|
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
Time Frame: 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)
|
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)
|
|
Receptor Occupancy in peripheral blood
Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (2 months), at end of treatment and 30 days after end of treatment (in total approximately 3 months). Each Cycle is 14 days.
|
Cycle 1 Day 1 through Cycle 4 Day 1 (2 months), at end of treatment and 30 days after end of treatment (in total approximately 3 months). Each Cycle is 14 days.
|
|
Immunomodulatory activity in subsets for AB928 in combination with mFOLFOX
Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (2 months), at end of treatment and 30 days after end of treatment (in total approximately 3 months). Each Cycle is 14 days.
|
Immunomodulatory activity will be assessed by aggregating data from biomarkers collected from peripheral blood samples
|
Cycle 1 Day 1 through Cycle 4 Day 1 (2 months), at end of treatment and 30 days after end of treatment (in total approximately 3 months). Each Cycle is 14 days.
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Medical Director, Arcus Biosciences, Inc.
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ARC-3 (AB928CSP0003)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan [SAP], Clinical Study Report [CSR]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.
For more information, please visit our website.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Colorectal Cancer
-
University of California, San FranciscoCompletedStage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC... and other conditionsUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminatedRectal Cancer | Colon Cancer | Cancer Survivor | Colorectal Adenocarcinoma | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC v8 | Stage I Colorectal Cancer AJCC v8 | Stage II Colorectal Cancer AJCC v8 | Stage... and other conditionsUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedStage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC... and other conditionsUnited States
-
M.D. Anderson Cancer CenterRecruitingColorectal Adenocarcinoma | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC v8 | Stage... and other conditionsUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedCancer Survivor | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC v8 | Stage I Colorectal Cancer AJCC v8 | Stage II Colorectal Cancer AJCC v8 | Stage IIA Colorectal Cancer AJCC v8 | Stage IIB Colorectal... and other conditionsUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...United States Department of DefenseActive, not recruitingColorectal Adenoma | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC v8 | Stage 0 Colorectal Cancer AJCC v8 | Stage I Colorectal Cancer AJCC v8 | Stage II Colorectal Cancer AJCC v8 | Stage IIA Colorectal... and other conditionsUnited States
-
City of Hope Medical CenterRecruitingColorectal Neoplasms | Colorectal Cancer | Colorectal Adenocarcinoma | Colorectal Cancer Stage II | Colorectal Cancer Stage III | Colorectal Cancer Stage IV | Colorectal Neoplasms Malignant | Colorectal Cancer Stage IUnited States, Japan, Italy, Spain
-
University of Roma La SapienzaCompletedColorectal Cancer Stage II | Colorectal Cancer Stage III | Colorectal Cancer Stage IV | Colorectal Cancer Stage 0 | Colorectal Cancer Stage IItaly
-
University of Southern CaliforniaNational Cancer Institute (NCI); AmgenTerminatedStage IV Colorectal Cancer AJCC v7 | Stage IVA Colorectal Cancer AJCC v7 | Stage IVB Colorectal Cancer AJCC v7 | Colorectal Adenocarcinoma | RAS Wild Type | Stage III Colorectal Cancer AJCC v7 | Stage IIIA Colorectal Cancer AJCC v7 | Stage IIIB Colorectal Cancer AJCC v7 | Stage IIIC Colorectal Cancer...United States
Clinical Trials on etrumadenant
-
Arcus Biosciences, Inc.Gilead SciencesCompletedHealthy ParticipantsUnited States
-
Washington University School of MedicineArcus Biosciences, Inc.Active, not recruitingNon Small Cell Lung Cancer | Non-small Cell Lung Cancer | Non-small Cell CarcinomaUnited States
-
Arcus Biosciences, Inc.Gilead SciencesCompleted
-
Arcus Biosciences, Inc.CompletedMelanoma | Renal Cell Carcinoma | Breast Cancer | Colorectal Cancer | Ovarian Cancer | Squamous Cell Carcinoma of the Head and Neck | Bladder Cancer | Endometrial Cancer | Non-small Cell Lung Cancer | Castration-resistant Prostate Cancer | Merkel Cell Carcinoma | GastroEsophageal CancerUnited States, Australia
-
Memorial Sloan Kettering Cancer CenterRecruitingSarcoma | Soft Tissue Sarcoma | Sarcoma,Soft Tissue | Dedifferentiated Liposarcoma | Recurrent Dedifferentiated Liposarcoma | Metastatic Dedifferentiated Liposarcoma | Unresectable Dedifferentiated LiposarcomaUnited States
-
Arcus Biosciences, Inc.Gilead SciencesActive, not recruitingLung Cancer | Non Small Cell Lung Cancer | Squamous Non Small Cell Lung Cancer | Nonsquamous Non Small Cell Lung CancerUnited States, Taiwan, Korea, Republic of, Australia, Singapore, Hong Kong, Canada
-
Surface OncologyArcus Biosciences, Inc.CompletedProstate Cancer | Metastatic Castration-resistant Prostate CancerUnited States
-
Jennifer ChoeArcus Biosciences, Inc.WithdrawnHead and Neck Cancer | Squamous Cell Carcinoma of Head and Neck | Oropharynx Cancer | Oral Cavity Cancer | Oropharynx Squamous Cell Carcinoma | Pharynx Cancer | Larynx Cancer | Hypopharynx Cancer | Oral Cavity Squamous Cell Carcinoma | Hypopharynx Squamous Cell CarcinomaUnited States
-
Weill Medical College of Cornell UniversityArcus Biosciences, Inc.Recruiting
-
Ono Pharma USA IncCompletedMultiple SclerosisUnited States, Belgium, Canada, Czech Republic, Germany, Greece, Japan, Poland, Russian Federation, Spain, Ukraine