Clinical trial NCT03720678: A Study to Evaluate Immunotherapy Combinations in Participants With Gastrointestinal Malignancies
Official title: A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Gastrointestinal Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: GastroEsophageal Cancer
Colorectal Cancer
Lead sponsor: Arcus Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2018-10-25
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 3+3 dose escalation
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: From first dose date to 90 days after the last dose (Approximately 1 year)
measure: Incidence of dose-limiting toxicities (DLTs) during dose escalation phase
timeFrame: From first dose date to 28 days after the first dose
Secondary outcomes:
measure: Plasma concentration of etrumadenant
timeFrame: 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)
measure: Percentage of participants with Objective Response as determined by Investigator according to RECIST v1.1
timeFrame: From study enrolment until participation discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 3-5 years)
measure: Percentage of participants with Disease Control (complete response, partial response, or stable disease) for > 6 months as determined by RECIST v1.1
timeFrame: From study enrolment until disease progression or loss of clinical benefit (up to approximately 3-5 years)
measure: Duration of Response as determined by the Investigator according to RECIST v1.1
timeFrame: 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)
measure: Progression Free Survival (PFS) as determined by the Investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: 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)
measure: Overall Survival (OS) as determined by the Investigator according to RECIST v1.1
timeFrame: From start of treatment up to death from any cause (up to approximately 3-5 years)
measure: Receptor Occupancy in peripheral blood
timeFrame: 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.
measure: Immunomodulatory activity in subsets for AB928 in combination with mFOLFOX
timeFrame: 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.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Rockville
country: United States
facility: Maryland Oncology Hematology
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Farmington Hills
country: United States
facility: QUEST Research Institute
state: Michigan
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Northeast
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Medical Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Albury
country: Australia
facility: Border Medical Oncology
state: New South Wales
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Darlinghurst
country: Australia
facility: The Kinghorn Cancer Centre
state: New South Wales
city: Kogarah
country: Australia
facility: St. George Private Hospital
state: New South Wales
city: Macquarie Park
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology and Oncology Group
state: Victoria
city: Malvern
country: Australia
facility: Cabrini Hospital
state: Victoria
Study officials:
affiliation: Arcus Biosciences, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: