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A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04104672
Recruitment Status : Recruiting
First Posted : September 26, 2019
Last Update Posted : September 30, 2022
Sponsor:
Information provided by (Responsible Party):
Arcus Biosciences, Inc.

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
Advanced Pancreatic Cancer Drug: AB680 Drug: Zimberelimab Drug: Nab-paclitaxel Drug: Gemcitabine 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 211 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
Actual Study Start Date : November 6, 2019
Estimated Primary Completion Date : January 30, 2024
Estimated Study Completion Date : January 30, 2024

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 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 Name: AB122

Drug: Nab-paclitaxel
Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
Other Name: Abraxane

Drug: Gemcitabine
Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
Other Name: 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 Name: AB122

Drug: Nab-paclitaxel
Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
Other Name: Abraxane

Drug: Gemcitabine
Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
Other Name: 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 Name: Abraxane

Drug: Gemcitabine
Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
Other Name: 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 Name: AB122

Drug: Nab-paclitaxel
Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
Other Name: Abraxane

Drug: Gemcitabine
Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
Other Name: Gemzar

Experimental: Dose Expansion (AB680 + Zimberelimab + NP/Gem): Cohort C (front-line/1L)
Participants with advance pancreatic cancer naïve to any prior treatment will receive AB680 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 Name: AB122

Drug: Nab-paclitaxel
Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
Other Name: Abraxane

Drug: Gemcitabine
Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
Other Name: Gemzar




Primary Outcome Measures :
  1. Number of participants with Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 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 [ Time Frame: From First dose to day 28 ]
  3. Number of participants with clinically significant changes in vital signs and clinical laboratory parameters [ Time Frame: From first dose date to 90 days after the last dose (approximately 1 year) ]

Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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, 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ 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


Other Outcome Measures:
  1. Pharmacodynamic effects of AB680 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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; 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 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

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 +1-510-462-3330 ClinicalTrialInquiry@arcusbio.com

Locations
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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    
Other Study ID Numbers: ARC-8 (AB680CSP0002)
First Posted: September 26, 2019    Key Record Dates
Last Update Posted: September 30, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan [SAP], Clinical Study Report [CSR]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Arcus Biosciences, Inc.:
AB680
Zimberelimab
Pancreatic cancer
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs