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A Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT03629756
Recruitment Status : Recruiting
First Posted : August 14, 2018
Last Update Posted : October 8, 2019
Sponsor:
Information provided by (Responsible Party):
Arcus Biosciences, Inc.

Tracking Information
First Submitted Date  ICMJE July 17, 2018
First Posted Date  ICMJE August 14, 2018
Last Update Posted Date October 8, 2019
Actual Study Start Date  ICMJE July 24, 2018
Estimated Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 10, 2018)
Safety of AB928 combination therapy [ Time Frame: From first dose date to 90 days after the last dose (approximately 1 year) ]
Number of treatment emergent adverse events according to CTCAE v5.0.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03629756 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2019)
  • AB928 Peak Plasma 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. at 30, 60 and 90 days, and 6 months) ]
    Measured using the area under the concentration-time curve from serum plasma collection and analysis
  • AB122 Peak Plasma 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. at 30, 60 and 90 days, and 6 months) ]
    Measured using the area under the concentration-time curve from serum plasma collection and analysis
  • AB928 Time of Peak 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. at 30, 60 and 90 days, and 6 months) ]
    Measured using the time to maximum concentration using non-compartmental methods from serum plasma collection and analysis
  • AB122 Time of Peak 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. at 30, 60 and 90 days, and 6 months) ]
    Measured using the time to maximum concentration using non-compartmental methods from serum plasma collection and analysis
  • AB928 PD [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), 30 and 90 days after treatment ]
    pharmacodynamic measures may be summarized by dose group and subject over time by aggregating data from exploratory biomarkers collected from research blood samples
  • AB122 PD [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), 30 and 90 days after treatment ]
    pharmacodynamic measures may be summarized by dose group and subject over time by aggregating data from exploratory biomarkers collected from research blood samples
  • AB122 immunogenicity [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), 30 and 90 days after treatment ]
    The number of subjects who develop anti-AB122 antibodies
  • 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 or Prostate Cancer Clinical Trials Working Group 3 (PCWG3)
Original Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2018)
  • AB928 Peak Plasma 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. at 30, 60 and 90 days, and 6 months) ]
    Measured using the area under the concentration-time curve from serum plasma collection and analysis
  • AB122 Peak Plasma 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. at 30, 60 and 90 days, and 6 months) ]
    Measured using the area under the concentration-time curve from serum plasma collection and analysis
  • AB928 Time of Peak 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. at 30, 60 and 90 days, and 6 months) ]
    Measured using the time to maximum concentration using non-compartmental methods from serum plasma collection and analysis
  • AB122 Time of Peak 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. at 30, 60 and 90 days, and 6 months) ]
    Measured using the time to maximum concentration using non-compartmental methods from serum plasma collection and analysis
  • AB928 PD [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), 30 and 90 days after treatment ]
    pharmacodynamic measures may be summarized by dose group and subject over time by aggregating data from exploratory biomarkers collected from research blood samples
  • AB122 PD [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), 30 and 90 days after treatment ]
    pharmacodynamic measures may be summarized by dose group and subject over time by aggregating data from exploratory biomarkers collected from research blood samples
  • AB122 immunogenicity [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), 30 and 90 days after treatment ]
    The number of subjects who develop anti-AB122 antibodies
  • 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.
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 the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies
Official Title  ICMJE A Phase 1 Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies
Brief Summary This is a Phase 1, open-label, dose-escalation study to evaluate the safety, tolerability, PK, PD and clinical activity of AB928 in combination with AB122 in participants with advanced malignancies.
Detailed Description

Dose escalation of AB928 in combination with AB122 will be assessed in participants with advanced malignancies. In this dose escalation combination study participants will receive oral administration of AB928 as well as iv infusion of AB122.

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 design.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-small Cell Lung Cancer
  • Squamous Cell Carcinoma of the Head and Neck
  • Breast Cancer
  • Colorectal Cancer
  • Melanoma
  • Bladder Cancer
  • Ovarian Cancer
  • Endometrial Cancer
  • Merkel Cell Carcinoma
  • GastroEsophageal Cancer
  • Renal Cell Carcinoma
  • Castration-resistant Prostate Cancer
Intervention  ICMJE
  • Drug: AB928
    AB928 is an A2aR and A2bR antagonist.
  • Drug: AB122
    AB122 is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1.
Study Arms  ICMJE
  • Experimental: Dose Escalation
    3+3 design, including a DLT evaluation period. Varying doses of AB928 in combination with the selected dose of AB122
    Interventions:
    • Drug: AB928
    • Drug: AB122
  • Experimental: Dose Expansion-RCC
    Selected Doses of AB928 + AB122
    Interventions:
    • Drug: AB928
    • Drug: AB122
  • Experimental: Dose Expansion-CRPC
    Selected Doses of AB928 + AB122
    Interventions:
    • Drug: AB928
    • Drug: AB122
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: March 1, 2019)
58
Original Estimated Enrollment  ICMJE
 (submitted: August 10, 2018)
18
Estimated Study Completion Date  ICMJE September 30, 2021
Estimated Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female participants ≥ 18 years
  2. Must have at least 1 measurable lesion per RECIST v1.1.
  3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  4. Must have received standard of care, including potentially curative available therapies or interventions.
  5. Confirm that an archival tissue sample is available and ≤ 6 months old; if not, a new biopsy of a tumor lesion must be obtained.
  6. Adequate organ and marrow function

    Dose escalation only:

  7. Pathologically confirmed non-small cell lung cancer, squamous cell carcinoma of the head and neck, renal cell carcinoma, breast cancer, colorectal cancer, melanoma, bladder cancer, ovarian cancer, endometrial cancer, Merkel cell carcinoma, or gastroesophageal cancer that is metastatic, advanced or recurrent with progression for which no alternative or curative therapy exists or standard therapy is not considered appropriate by the participant and treating physician (reason must be documented in medical records).

    Dose expansion only:

  8. Patients with advanced clear-cell RCC or metastatic castration-resistant prostate cancer who must have relapsed during anti-PD-1 monotherapy
  9. ccRCC patients may have received up to 2 prior lines of therapy, one of which must have included an anti-PD-(L)1 based therapy and must not have progressed within 16 weeks during an anti-PD-(L)1 therapy.
  10. mCRPC patients must have progressed during or following treatment with an androgen synthesis inhibitor who have also had one prior line of a taxane-containing regimen or the physician and participant consider the taxane-containing regimen to be inappropriate. mCRPC patients must be naive to any immunotherapy (including but not limited to anti-PD-(L)1 or anti-CTLA-4 antogonists, sipuleucel-T, etc.).

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 90 days after the last dose of AB928 in combination with AB122.
  5. Any active or documented history of autoimmune disease, or history of a syndrome that required systemic steroids or immunosuppressive medications, except for vitiligo or resolved childhood asthma/atopy. Participants with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study.
  6. Prior malignancy active within the previous year 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 cancer.
  7. Dose escalation: Prior treatment with an anti-PD-L1, anti-PD-1, anti-CTLA-4, or other immune checkpoint inhibitor or agonist as a monotherapy or in combination;
  8. Use of other investigational drugs (drugs not marketed for any indication) within 28 days or at least 5 half-lives (whichever is longer) before 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 Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03629756
Other Study ID Numbers  ICMJE AB928CSP0005
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 October 2019

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