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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 : Recruiting
First Posted : October 25, 2018
Last Update Posted : November 26, 2019
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 November 26, 2019
Actual Study Start Date  ICMJE October 15, 2018
Estimated Primary Completion Date July 30, 2020   (Final data collection date for primary outcome measure)
Current 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03720678 on ClinicalTrials.gov Archive Site
Current 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
Original Secondary Outcome Measures  ICMJE Same as current
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 AB928 in combination with mFOLFOX in participants with advanced metastatic gastroesophageal Cancer (GEC) or colorectal cancer (CRC).
Detailed Description

Dose escalation of AB928 in combination with mFOLFOX at standard doses will be assessed in participants with advanced metastatic GEC or CRC. In this dose escalation combination study participants will receive oral administration of AB928 as well as iv infusion of mFOLFOX.

Dose expansion of AB928 in combination with mFOLFOX at standard doses will be assessed in participants with advanced metastatic GEC or CRC. The dose of AB928 used will be determined based on the findings from the dose-escalation phase.

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: AB928
    AB928 is an A2aR and A2bR antagonist.
  • 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 dose expansion dose level will be determined in this part with escalating doses of AB928 in combination with the standard mFOLFOX chemotherapy regimen in participants with gastroesophageal or colorectal cancer.
    Interventions:
    • Drug: AB928
    • Drug: mFOLFOX
  • Experimental: Dose Expansion-GE
    The dose given in expansion will be determined from the dose escalation part. AB928 will be given in combination with the standard mFOLFOX chemotherapy regimen in participants with gastroesophageal cancer
    Interventions:
    • Drug: AB928
    • Drug: mFOLFOX
  • Experimental: Dose Expansion-CRC
    The dose given in expansion will be determined from the dose escalation part. AB928 will be given in combination with the standard mFOLFOX chemotherapy regimen in participants with colorectal cancer
    Interventions:
    • Drug: AB928
    • 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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 24, 2018)
98
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 30, 2021
Estimated Primary Completion Date July 30, 2020   (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 ≤ 6 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. 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 AB928 in combination with mFOLFOX.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. Participants who are eligible for potentially curative available therapies or interventions.
  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: Medical Director 510-694-6200 ClinicalTrialInquiry@arcusbio.com
Listed Location Countries  ICMJE United States,   Australia
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 November 2019

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