A Study to Evaluate Immunotherapy Combinations in Participants With Gastrointestinal Malignancies

Colorectal Cancer Clinical Trial

Official title:

A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Gastrointestinal Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03720678
• Other study ID #: ARC-3 (AB928CSP0003)
• Status: Completed
• Phase: Phase 1
• Start date: November 18, 2018
• Est. completion date: June 25, 2021

Study information

• Verified date: August 2023
• Source: Arcus Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 cancer (CRC).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: June 25, 2021
• Est. primary completion date: January 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• GastroEsophageal Cancer

Intervention

Drug:
• etrumadenant
Etrumadenant is an A2aR and A2bR antagonist.
• mFOLFOX
Oxaliplatin, Leucovorin and 5-fluorouracil given as part of standard mFOLFOX chemotherapy regimen

Locations

Country	Name	City	State
Australia	Border Medical Oncology	Albury	New South Wales
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	The Kinghorn Cancer Centre	Darlinghurst	New South Wales
Australia	Peninsula & South Eastern Haematology and Oncology Group	Frankston	Victoria
Australia	St. George Private Hospital	Kogarah	New South Wales
Australia	Macquarie University Hospital	Macquarie Park	New South Wales
Australia	Cabrini Hospital	Malvern	Victoria
United States	Texas Oncology - Austin Midtown	Austin	Texas
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	QUEST Research Institute	Farmington Hills	Michigan
United States	Texas Oncology - Fort Worth Cancer Center	Fort Worth	Texas
United States	Prisma Health	Greenville	South Carolina
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Yale Cancer Center	New Haven	Connecticut
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Maryland Oncology Hematology	Rockville	Maryland
United States	Texas Oncology - San Antonio Medical Center	San Antonio	Texas
United States	Texas Oncology - San Antonio Northeast	San Antonio	Texas
United States	Arizona Clinical Research Center	Tucson	Arizona
United States	Texas Oncology - Tyler	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Arcus Biosciences, Inc.

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events (AEs)		From first dose date to 90 days after the last dose (Approximately 1 year)
Primary	Incidence of dose-limiting toxicities (DLTs) during dose escalation phase		From first dose date to 28 days after the first dose
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Overall Survival (OS) as determined by the Investigator according to RECIST v1.1		From start of treatment up to death from any cause (up to approximately 3-5 years)
Secondary	Receptor Occupancy in peripheral blood		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.
Secondary	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	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.

External Links

•   ARC-3 - Lay Summary (English Version)