A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies

Sponsor
Arcus Biosciences, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04104672
Collaborator
(none)
150
20
4
50.8
7.5
0.1

Study Details

Study Description

Brief Summary

This is a Phase 1, open-label, dose-escalation, and dose-expansion, with a gated randomization portion, study to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic and clinical activity of AB680 in combination with Zimberelimab (AB122), nab-paclitaxel and gemcitabine in participants with advanced pancreatic cancer.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

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

In the dose expansion portion of the study in front-line (1L) pancreatic patients, participants will receive AB680 at the RP2D determined from the dose escalation study in combination with Zimberelimab at the RP2D and nab-paclitaxel and gemcitabine at standard doses or AB680 at the RP2D in combination with nab-paclitaxel and gemcitabine at standard doses. In the dose-expansion portion of the study in second-line (2L) pancreatic patients, participants will receive AB680 at the RP2D determined from the dose-escalation study in combination with Zimberelimab at the RP2D and nab-paclitaxel and gemcitabine at standard doses.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
150 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
3+3 Dose escalation design3+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
Actual Study Start Date :
Nov 6, 2019
Anticipated Primary Completion Date :
Jan 30, 2024
Anticipated Study Completion Date :
Jan 30, 2024

Arms and Interventions

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 Zimberelimab 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: Zimberelimab
Zimberelimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1.
Other Names:
  • AB122
  • Drug: Nab-paclitaxel
    Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
    Other Names:
  • Abraxane
  • Drug: Gemcitabine
    Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
    Other Names:
  • Gemzar
  • Experimental: Dose Expansion(AB680+Zimberelimab+nab-paclitaxel(NP) & gemcitabine (Gem):Cohort A1 (front-line/1L)

    Participants with advance pancreatic cancer, naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) combined with Zimberelimab and the standard nab-paclitaxel (NP) and gemcitabine (Gem) (NP/Gem) chemotherapy regimen

    Drug: AB680
    AB680 is a Cluster of Differentiation (CD)73 Inhibitor.

    Drug: Zimberelimab
    Zimberelimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1.
    Other Names:
  • AB122
  • Drug: Nab-paclitaxel
    Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
    Other Names:
  • Abraxane
  • Drug: Gemcitabine
    Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
    Other Names:
  • Gemzar
  • Experimental: Dose Expansion (AB680 + NP/Gem): Cohort A2 (front-line/1L)

    Participants with advance pancreatic cancer who are naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) and the standard NP/Gem chemotherapy regimen.

    Drug: AB680
    AB680 is a Cluster of Differentiation (CD)73 Inhibitor.

    Drug: Nab-paclitaxel
    Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
    Other Names:
  • Abraxane
  • Drug: Gemcitabine
    Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
    Other Names:
  • Gemzar
  • Experimental: Dose Expansion (AB680 + Zimberelimab + NP/Gem): Cohort B (second-line/2L)

    Participants with advance pancreatic cancer who have received 1 prior line of treatment will receive AB680 (at the RP2D identified during dose escalation) combined with Zimberelimab and NP-Gem chemotherapy regimen.

    Drug: AB680
    AB680 is a Cluster of Differentiation (CD)73 Inhibitor.

    Drug: Zimberelimab
    Zimberelimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1.
    Other Names:
  • AB122
  • Drug: Nab-paclitaxel
    Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
    Other Names:
  • Abraxane
  • Drug: Gemcitabine
    Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
    Other Names:
  • Gemzar
  • Outcome Measures

    Primary Outcome Measures

    1. Number of participants with Treatment Emergent Adverse Events (TEAEs) [From first dose date to 90 days after the last dose (approximately 1 year)]

      Safety will be assessed by monitoring adverse events and clinically relevant changes in 12 lead Electrocardiogram (ECG) and Physical examination findings

    2. Number of Participants With Dose Limiting Toxicities [From First dose to day 28]

    Secondary Outcome Measures

    1. Duration of response [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

    2. Disease control rate [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

    3. Overall survival [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

    4. Progression free survival [First dose date to first progression/death, up to 1 year]

      Number of participants without disease progression per RECIST v1.1

    5. AB680 peak plasma concentration (Cmax) [Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 36, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose]

      Peak plasma concentration (Cmax) of AB680

    6. Zimberelimab peak plasma concentration (Cmax) [Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose]

      Peak plasma concentration (Cmax) of Zimberelimab

    7. AB680 time of peak concentration (Tmax) [Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 36, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose]

      Time of peak concentration (Tmax) of AB680

    8. Zimberelimab time of peak concentration (Tmax) [Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose]

      Time of peak concentration of Zimberelimab

    9. AB680 area under the plasma concentration versus time curve (AUC) [Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 36, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose]

      Area under the plasma concentration versus time curve (AUC) of AB680

    10. Zimberelimab area under the plasma concentration versus time curve (AUC) [Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose]

      Area under the plasma concentration versus time curve (AUC) of Zimberelimab

    11. Immunogenicity indicators: anti-drug antibodies (ADA) [Day 1, day 15, day 29, day 57, day 85, day 197, day 309, and day 421]

      Number of participants who develop anti-drug antibodies to Zimberelimab

    12. Overall response rate [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

    Other Outcome Measures

    1. Pharmacodynamic effects of AB680 [Day 1, day 2, day 8, day 15, day 29, day 36, day 43, day 57, and day 85]

      Enzymatic activity of CD73 measured in participant blood samples

    2. AB680 cytokines [Day 1, day 2, day 8, day 15, day 29, day 36, day 43, day 57, and day 85]

      Cytokines may be summarized by dose group and subject over time by aggregating data from exploratory biomarkers collected from peripheral blood samples

    3. AB680 immunophenotyping [Day 1, day 2, day 8, day 15, day 29, day 36, day 43, day 57, and day 85]

      Immunophenotyping may be summarized by dose group and subject over time by aggregating data from exploratory biomarkers collected from peripheral blood samples

    4. AB680 gene expression [Day 1, day 2, day 8, day 15, day 29, day 36, day 43, day 57, and day 85]

      Gene expression may be summarized by dose group and subject over time by aggregating data from exploratory biomarkers collected from peripheral blood samples

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    6. 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

    7. 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

    8. 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

    9. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

    10. Confirmation that an archival tissue sample is available; if not, a new biopsy of a tumor must be obtained

    11. 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

    12. 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

    13. 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

    14. Adequate organ and marrow function

    Exclusion Criteria:
    1. Use of any live attenuated 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Angeles Clinic Los Angeles California United States 90025
    2 UCLA Hematology Oncology Santa Monica California United States 90404
    3 Yale Cancer Center New Haven Connecticut United States 06511
    4 Investigator Site New Haven Connecticut United States 06520
    5 Investigator Site 1 Orange City Florida United States 32763
    6 Investigator Site Orange City Florida United States 32763
    7 Investigator Site Plantation Florida United States 33322
    8 Washington University School of Medicine - Siteman Cancer Center Saint Louis Missouri United States 63110
    9 NYU Cancer Institute New York New York United States 10016
    10 Columbia University New York New York United States 10032
    11 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    12 Stephenson Cancer Center Oklahoma City Oklahoma United States 73104
    13 Hospital of the University of Pennsylvania Philadelphia Pennsylvania United States 19104
    14 Thomas Jefferson University Hospital Philadelphia Pennsylvania United States 19107
    15 UPMC Hillman Cancer Center Pittsburgh Pennsylvania United States 15232
    16 Sarah Canon Research Institute Nashville Tennessee United States 37203
    17 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    18 Investigator Site San Antonio Texas United States 78229
    19 Investigator Site Spokane Washington United States 99208
    20 University of Wisconsin Madison Wisconsin United States 53792

    Sponsors and Collaborators

    • Arcus Biosciences, Inc.

    Investigators

    • Study Director: Medical Director, Arcus Biosciences, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Arcus Biosciences, Inc.
    ClinicalTrials.gov Identifier:
    NCT04104672
    Other Study ID Numbers:
    • AB680CSP0002
    First Posted:
    Sep 26, 2019
    Last Update Posted:
    May 3, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 3, 2022