GastroEsophageal CancerPhase 1NCT03720678
A Study to Evaluate Immunotherapy Combinations in Participants With Gastrointestinal Malignancies
A Phase 1 study testing etrumadenant and mFOLFOX in people with GastroEsophageal Cancer and Colorectal Cancer, run by Arcus Biosciences, Inc. at 24 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GastroEsophageal Cancer, Colorectal Cancer
- What is being tested?
- etrumadenant and mFOLFOX
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 24 sitesin 2 countries
- Study dates
- 18 Nov 2018to 25 Jun 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
24 sites in 2 countries.
24 sites in 2 countries
United States17 sites
Texas Oncology - Austin Midtown
Austin, Texas, 78705
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
Rocky Mountain Cancer Centers
Denver, Colorado, 80218
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
QUEST Research Institute
Farmington Hills, Michigan, 48334
Texas Oncology - Fort Worth Cancer Center
Fort Worth, Texas, 76104
Prisma Health
Greenville, South Carolina, 29605
Carolina BioOncology Institute
Huntersville, North Carolina, 28078
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
Yale Cancer Center
New Haven, Connecticut, 06520
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 16148
Maryland Oncology Hematology
Rockville, Maryland, 20850
Texas Oncology - San Antonio Northeast
San Antonio, Texas, 78217
Texas Oncology - San Antonio Medical Center
San Antonio, Texas, 78240
Arizona Clinical Research Center
Tucson, Arizona, 85715
Texas Oncology - Tyler
Tyler, Texas, 75702
Australia7 sites
Border Medical Oncology
Albury, New South Wales, 2640
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
The Kinghorn Cancer Centre
Darlinghurst, New South Wales, 2010
Peninsula & South Eastern Haematology and Oncology Group
Frankston, Victoria, 3199
St. George Private Hospital
Kogarah, New South Wales, 2217
Macquarie University Hospital
Macquarie Park, New South Wales, 2109
Cabrini Hospital
Malvern, Victoria, 3144
About this study
Official title: A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Gastrointestinal Malignancies
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).
Read the 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.
- Conditions
- GastroEsophageal Cancer, Colorectal Cancer
- Being tested
- etrumadenant, mFOLFOX
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
etrumadenantDrug
Also called AB928
Etrumadenant is an A2aR and A2bR antagonist.
mFOLFOXDrug
Oxaliplatin, Leucovorin and 5-fluorouracil given as part of standard mFOLFOX chemotherapy regimen
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: 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 Receives: Drug: etrumadenant; Drug: mFOLFOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events (AEs)
Measured: From first dose date to 90 days after the last dose (Approximately 1 year)
Incidence of dose-limiting toxicities (DLTs) during dose escalation phase
Measured: From first dose date to 28 days after the first dose
Secondary outcomes (8)
Plasma concentration of etrumadenant
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Overall Survival (OS) as determined by the Investigator according to RECIST v1.1
Measured: From start of treatment up to death from any cause (up to approximately 3-5 years)
Receptor Occupancy in peripheral blood
Measured: 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
Immunomodulatory activity will be assessed by aggregating data from biomarkers collected from peripheral blood samples
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2018
- Study start18 Nov 2018
- Primary completion27 Jan 2021
- Study completion25 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GastroEsophageal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 3+3 dose escalation
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arcus Biosciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Arcus Biosciences, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03720678
- Sponsor's protocol ID
- ARC-3 (AB928CSP0003)
- Status last verified
- May 2024
- First submitted
- 24 Oct 2018
- Last updated
- 24 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Gastrointestinal Malignancies
- ClinicalTrials.gov ID
- NCT03720678
- Acronym / sponsor ID
- ARC-3 (AB928CSP0003)
- Conditions
- GastroEsophageal Cancer, Colorectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Arcus Biosciences, Inc.Industry (pharma, biotech, devices)
- Study start
- 18 Nov 2018 (actual)
- Primary completion
- 27 Jan 2021 (actual)
- Study completion
- 25 Jun 2021 (actual)
- First posted
- 25 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 3+3 dose escalation
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Drug: etrumadenant, Drug: mFOLFOXDose 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. |
| Dose Expansion-GE | Experimental | Drug: etrumadenant, Drug: mFOLFOXThe 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 |
| Dose Expansion-CRC | Experimental | Drug: etrumadenant, Drug: mFOLFOXThe 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| etrumadenantAlso: AB928Etrumadenant is an A2aR and A2bR antagonist. | Drug | Dose Escalation, Dose Expansion-CRC, Dose Expansion-GE |
| mFOLFOXOxaliplatin, Leucovorin and 5-fluorouracil given as part of standard mFOLFOX chemotherapy regimen | Drug | Dose Escalation, Dose Expansion-CRC, Dose Expansion-GE |
Primary outcome
Incidence of Adverse Events (AEs)
Time frame: 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
8 secondary outcomes
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)
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)
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)
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)
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)
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)
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2024.
- ARC-3 - Lay Summary (English Version)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Arcus Biosciences, Inc.
24 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing etrumadenant and mFOLFOX in people with GastroEsophageal Cancer and Colorectal Cancer, run by Arcus Biosciences, Inc. at 24 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events (AEs) (time frame: From first dose date to 90 days after the last dose (Approximately 1 year)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2024; AzTrials last refreshed its copy on 6 Nov 2026.