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A Study to Evaluate Immunotherapy Combinations in Participants With Gastrointestinal Malignancies

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ClinicalTrials.gov Identifier: NCT03720678
Recruitment Status : Completed
First Posted : October 25, 2018
Last Update Posted : June 29, 2021
Sponsor:
Information provided by (Responsible Party):
Arcus Biosciences, Inc.

Tracking Information
First Submitted Date  ICMJE October 24, 2018
First Posted Date  ICMJE October 25, 2018
Last Update Posted Date June 29, 2021
Actual Study Start Date  ICMJE November 18, 2018
Actual Primary Completion Date January 27, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 30, 2020)
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 24, 2018)
Number of Participants with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0 [ Time Frame: From first dose date to 90 days after the last dose (Approximately 1 year) ]
Number of Participants Treated with AB928 in Combination with mFOLFOX with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2020)
  • 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 enrollment until participation discontinuation, first occurence of progressive disease, or death from any cause, whichever occurs frist (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 enrollment 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 occurence 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: 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. ]
  • T-cell immunophenotyping in peripheral blood [ Time Frame: 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. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2018)
  • AB928 Pharmacokinetic (PK) Concentration: Cmax [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and every 30 days until 6 months post last dose (i.e. in total approximately 6 months) ]
    Measured using the area under the concentration-time curve from serum plasma collection and analysis
  • AB928 Pharmacokinetic (PK) Concentration: Tmax [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and every 30 days until 6 months post last dose (i.e. in total approximately 6 months) ]
    Measured using the time to maximum concentration using non-compartmental methods from serum plasma collection and analysis
  • Clinical Activity of combination therapy [ Time Frame: Recorded at Baseline (Screening), every 8 weeks until progression (approximately 6 months, however can be longer) ]
    Tumor assessments over time will be measured using RECIST v1.0.
  • AB928 Receptor Occupancy [ Time Frame: Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days after treatment ends (in total approximately 6 months). Each Cycle is 28 days. ]
    Receptor Occupancy May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • AB928 Immunophenotyping [ Time Frame: Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days after treatment ends (in total approximately 6 months). Each Cycle is 28 days. ]
    Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • AB928 Gene Expression [ Time Frame: Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days after treatment ends (in total approximately 6 months). Each Cycle is 28 days. ]
    Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
  • AB928 Cytokines [ Time Frame: Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days after treatment ends (in total approximately 6 months). Each Cycle is 28 days. ]
    Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Immunotherapy Combinations in Participants With Gastrointestinal Malignancies
Official Title  ICMJE A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Gastrointestinal Malignancies
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
3+3 dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • GastroEsophageal Cancer
  • Colorectal Cancer
Intervention  ICMJE
  • Drug: etrumadenant
    Etrumadenant is an A2aR and A2bR antagonist.
    Other Name: AB928
  • Drug: mFOLFOX
    Oxaliplatin, Leucovorin and 5-fluorouracil given as part of standard mFOLFOX chemotherapy regimen
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: etrumadenant
    • Drug: mFOLFOX
  • 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
    Interventions:
    • Drug: etrumadenant
    • Drug: mFOLFOX
  • 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
    Interventions:
    • Drug: etrumadenant
    • Drug: mFOLFOX
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 25, 2021)
44
Original Estimated Enrollment  ICMJE
 (submitted: October 24, 2018)
98
Actual Study Completion Date  ICMJE June 25, 2021
Actual Primary Completion Date January 27, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female participants ≥ 18 years
  2. Histologically confirmed gastroesophageal cancer or colorectal cancer that is metastatic, advanced or recurrent with progression
  3. Participants for whom mFOLFOX is considered appropriate therapy
  4. Must have at least 1 measurable lesion per RECIST v1.1.
  5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  6. Must have received standard of care, including potentially curative available therapies or interventions.
  7. Confirm that an archival tissue sample is available and ≤ 24 months old; if not, a new biopsy of a tumor lesion must be obtained.
  8. Adequate organ and marrow function

Exclusion Criteria:

  1. Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of investigational product.
  2. 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.
  3. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  4. Untreated or symptomatic CNS disease
  5. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with screening visit through 30 days after the last dose of etrumadenant in combination with mFOLFOX.
  6. 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.

    1. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
    2. 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.
  7. 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.
  8. Oxaliplatin-based therapy as the most recent regimen prior to enrolling in the study, except if prior oxaliplatin-based therapy was received as the most recent regimen in the adjuvant setting and completed ≥ 6 months prior to study enrollment.
  9. 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 considered not clinically significant by the Medical Monitor and Investigator.
  10. Use of other investigational drugs (drugs not marketed for any indication) within 28 days of investigational product administration.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03720678
Other Study ID Numbers  ICMJE AB928CSP0003
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Arcus Biosciences, Inc.
Study Sponsor  ICMJE Arcus Biosciences, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Arcus Biosciences, Inc.
PRS Account Arcus Biosciences, Inc.
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP