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Trial record 1 of 2 for:    AB680
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A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies

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ClinicalTrials.gov Identifier: NCT04104672
Recruitment Status : Not yet recruiting
First Posted : September 26, 2019
Last Update Posted : October 18, 2019
Sponsor:
Information provided by (Responsible Party):
Arcus Biosciences, Inc.

Brief Summary:
This is a Phase 1, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic and clinical activity of AB680 in combination with AB122, nab-paclitaxel and gemcitabine in participants with advanced pancreatic cancer.

Condition or disease Intervention/treatment Phase
Advanced Pancreatic Cancer Drug: AB680 Drug: AB122 Phase 1

Detailed Description:

Dose escalation of AB680 in combination with AB122, nab-paclitaxel and gemcitabine will be assessed in participants with advanced pancreatic cancer. In this dose escalation combination study, participants will receive escalating doses of AB680 in combination with AB122 at the recommended phase 2 dose (RP2D), and nab-paclitaxel and gemcitabine at standard doses in participants with advanced pancreatic cancer. AB680, AB122, nab-paclitaxel and gemcitabine are all administered via iv infusion.

Overall duration of treatment will depend on how well the treatment is tolerated. Treatment may continue until progressive disease, unacceptable toxicity or other reasons specified in the protocol.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 3+3 Dose escalation design
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study to Evaluate the Safety and Tolerability of AB680 Combination Therapy in Participants With Gastrointestinal Malignancies
Estimated Study Start Date : October 21, 2019
Estimated Primary Completion Date : April 26, 2022
Estimated Study Completion Date : April 26, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 AB680 in combination with AB122 at the recommended phase 2 dose (RP2D) and the standard nab-paclitaxel and gemcitabine chemotherapy regimen in participants with advanced pancreatic cancer.
Drug: AB680
AB680 is a Cluster of Differentiation (CD)73 Inhibitor.

Drug: AB122
AB122 is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1.

Experimental: Dose Expansion
The dose given in dose expansion will be determined from the dose escalation part. AB680 will be given in combination with AB122 at the recommend phase 2 dose (RP2D) and the standard nab-paclitaxel and gemcitabine chemotherapy regimen in participants with advanced pancreatic cancer.
Drug: AB680
AB680 is a Cluster of Differentiation (CD)73 Inhibitor.

Drug: AB122
AB122 is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1.




Primary Outcome Measures :
  1. 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 AB680 in combination with AB122 and nab-paclitaxel and gemcitabine with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0


Secondary Outcome Measures :
  1. AB680 Peak Plasma Concentration (Cmax) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 85, 30 days after last dose, and 90 days after last dose ]
    Peak Plasma Concentration (Cmax) of AB680

  2. AB122 Peak Plasma Concentration (Cmax) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, 30 days after last dose, and 90 days after last dose ]
    Peak Plasma Concentration (Cmax) of AB122

  3. AB680 Time of Peak Concentration (Tmax) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 85, 30 days after last dose, and 90 days after last dose ]
    Time of Peak Concentration (Tmax) of AB680

  4. AB122 Time of Peak Concentration (Tmax) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, 30 days after last dose, and 90 days after last dose ]
    Time of Peak Concentration of AB122

  5. AB680 Area Under the Plasma Concentration Versus Time Curve (AUC) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 85, 30 days after last dose, and 90 days after last dose ]
    Area Under the Plasma Concentration Versus Time Curve (AUC) of AB680

  6. AB122 Area Under the Plasma Concentration Versus Time Curve (AUC) [ Time Frame: Day 1 (sequential), Day 2, Day 3, Day 8, Day 15, Day 29, Day 43, Day 57, Day 85, 30 days after last dose, and 90 days after last dose ]
    Area Under the Plasma Concentration Versus Time Curve (AUC) of AB122

  7. Pharmacodynamic Effects of AB680 [ Time Frame: Day 1, Day 2, Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 85 and 30 days after last dose ]
    Enzymatic Activity of CD73 Measured in Participant Blood Samples

  8. Immunogenicity Indicators: Anti-Drug Antibodies (ADA) [ Time Frame: Day 1, Day 15, Day 29, Day 57, Day 85, 30 days after last dose, and 90 days after last dose ]
    Number of Participants who Develop Antidrug Antibodies to AB122

  9. Overall Response Rate [ Time Frame: First Dose Date to Progression or Last Tumor Assessment, up to 1 year ]
    Number of Participants with Complete or Partial Response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.1

  10. Duration of Response [ Time Frame: Start Date of Response to First Progression/Death, up to 1 year ]
    Time at Which Response Criteria are Met for Complete Response or Partial Response (Whichever Occurs First) Until the First Date of Recurrence, Progression or Death per RECIST v1.1

  11. Disease Control Rate [ Time Frame: First Dose Date to First Progression/Death, up to 1 year ]
    Number of Participants with Complete Response, Partial Response, or Stable Disease for Greater Than 6 Months per RECIST v1.1

  12. Progression Free Survival [ Time Frame: First Dose Date to First Progression/Death, up to 1 year ]
    Number of Participants Without Disease Progression per RECIST v1.1

  13. Overall Survival [ Time Frame: First Dose Date to Date of Death, up to 1 year ]
    Overall Survival Rate, Defined as Time Between First Dose Date and Date of Death


Other Outcome Measures:
  1. AB680 Cytokines [ Time Frame: Day 1, Day 2, Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 85 and 30 days after last dose ]
    Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples

  2. AB680 Immunophenotyping [ Time Frame: Day 1, Day 2, Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 85 and 30 days after last dose ]
    Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples

  3. AB680 Gene Expression [ Time Frame: Day 1, Day 2, Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 85 and 30 days after last dose ]
    Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Capable of giving signed informed consent
  2. Male or female participants ≥ 18 years of age at the time of screening
  3. Negative serum pregnancy test at screening and prior to dosing on Cycle 1 Day 1; negative serum or urine pregnancy test on the first day of each subsequent treatment period
  4. Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma
  5. Naïve to any prior treatment, including chemotherapy, biological therapy, or targeted therapy for metastatic disease

    1. Prior adjuvant therapy (including chemotherapy and/or radiotherapy) for pancreatic adenocarcinoma is permitted if neoadjuvant or adjuvant therapy was completed at least 6 months prior to study enrollment. Prior adjuvant therapy may include Nab- paclitaxel or gemcitabine
    2. Participants initially diagnosed with locally advanced pancreatic cancer who have undergone chemotherapy then resection and had no evidence of disease are eligible if relapse of metastatic disease has occurred and if the last dose of chemotherapy was received more than 6 months before study entry
  6. Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The measurable lesion must be outside of a radiation field if the participant received prior radiation
  7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  8. Confirmation that an archival tissue sample is available and ≤ 6 months old; if not, a new biopsy of a tumor must be obtained
  9. Immunosuppressive doses of systemic medications, such as corticosteroids or absorbed topical corticosteroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks (14 days) before investigational product administration. Physiologic doses of corticosteroids (≤ 10 mg/day of prednisone or its equivalent) or short pulses of corticosteroids (≤ 3 days) may be permitted
  10. Prior surgery that required general anesthesia or other major surgery as defined by the Investigator must be completed at least 4 weeks before investigational product administration
  11. Negative tests for hepatitis B surface antigen, hepatitis C virus antibody (or hepatitis C qualitative ribonucleic acid [RNA; qualitative]), and human immunodeficiency virus (HIV)-1 and HIV-2 antibody at screening
  12. 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
  3. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  4. Any active autoimmune disease or a 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
  5. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04104672


Contacts
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Contact: Medical Director 510-694-6200 ClinicalTrialInquiry@arcusbio.com

Locations
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United States, Tennessee
United States, Tennessee Not yet recruiting
Nashville, Tennessee, United States, 53705
Contact: Principal Investigator         
Sponsors and Collaborators
Arcus Biosciences, Inc.
Investigators
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Study Director: Medical Director Arcus Biosciences, Inc.

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Responsible Party: Arcus Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT04104672     History of Changes
Other Study ID Numbers: AB680CSP0002
First Posted: September 26, 2019    Key Record Dates
Last Update Posted: October 18, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No