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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03629756
Recruitment Status : Active, not recruiting
First Posted : August 14, 2018
Last Update Posted : November 5, 2020
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 November 5, 2020
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: January 31, 2020)
  • Percentage of participants with Adverse Events [ Time Frame: From first dose date to 90 days after the last dose (approximately 1 year) ]
  • Percentage of participants who experience a Dose Limiting Toxicity [ Time Frame: From first study treatment administration through Day 28 ]
Original 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2020)
  • Etrumadenant Peak Plasma Concentration: Cmax [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 1 year). ]
  • Zimberelimab Peak Plasma Concentration: Cmax [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 1 year). ]
  • Etrumadenant Time of Peak Concentration: Tmax [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 1 year). ]
  • Zimberelimab Time of Peak Concentration: Tmax [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 1 year). ]
  • Percentage of participants with anti-drug antibodies to zimberelimab [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), at end of treatment, and 30 and 90 days post last dose (approximately 1 year). ]
  • Progression Free Survival (PFS) as determined by Investigator according to Prostate Cancer Working Group 3 (PCWG3) for prostate adenocarcinoma and per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for all other tumor types [ Time Frame: From start of treatment up to the first occurrence of progressive disease or death from any cause (approximately 6 months, however can be longer). ]
  • Overall Survival (OS) as determined by the Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types [ Time Frame: From study start of treatment up to death from any cause (up to approximately 1-3 years) ]
  • Duration of Response as determined by the Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types [ Time Frame: 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 (approximately 1 year) ]
  • Percentage of Participants with Disease Control (complete response, partial response, or stable disease) for >6 months as determined by the Investigator per PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types [ Time Frame: From study enrollment until disease progression or loss of clinical benefit (approximately 1 year) ]
  • Percentage of participants with Objective Response as determined by Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types [ Time Frame: From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 1 year) ]
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 and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and clinical activity of etrumadenant (AB928) in combination with zimberelimab (AB122) (an anti-PD-1 antibody) in participants with advanced malignancies.
Detailed Description

In the dose-escalation phase, escalating doses of etrumadenant in combination with zimberelimab will be assessed in participants with advanced malignancies. Eligible participants will receive oral administration of etrumadenant as well as IV infusion of zimberelimab. 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 RDE in combination with zimberelimab may be assessed in participants with advanced clear-cell renal cell carcinoma (RCC) or metastatic castrate-resistant adenocarcinoma of the prostate (mCRPC).

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: Etrumadenant
    Etrumadenant is an A2aR and A2bR antagonist.
    Other Name: AB928
  • Drug: Zimberelimab
    Zimberelimab is a fully human anti-PD-1 monoclonal antibody.
    Other Name: AB122
Study Arms  ICMJE
  • Experimental: Dose Escalation
    3+3 design, including a DLT evaluation period. Etrumadenant RDE will be determined in this part with escalating doses of etrumadenant in combination with a fixed dose of zimberelimab.
    Interventions:
    • Drug: Etrumadenant
    • Drug: Zimberelimab
  • Experimental: Dose Expansion-advanced clear-cell RCC
    Etrumadenant at RDE + zimberelimab
    Interventions:
    • Drug: Etrumadenant
    • Drug: Zimberelimab
  • Experimental: Dose Expansion-mCRPC
    Etrumadenant at RDE + zimberelimab
    Interventions:
    • Drug: Etrumadenant
    • Drug: Zimberelimab
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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 31, 2020)
44
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. Biopsy must not put participant at undue risk and procedure must not be more invasive than a core biopsy.
  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 mCRPC.
  9. Clear-cell RCC 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, and 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 etrumadenant in combination with zimberelimab.
  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 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 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 November 2020

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