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

NCT ID: NCT04104672

Last Updated: 2026-01-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

196 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-06

Study Completion Date

2027-05-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Advanced Pancreatic Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

3+3 Dose escalation design
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

AB680

Intervention Type DRUG

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

Zimberelimab

Intervention Type DRUG

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

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Gemcitabine

Intervention Type DRUG

Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Dose Expansion (AB680+zimberelimab+ NP/Gem): Cohort A (front-line/1L)

Participants with advanced 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

Group Type EXPERIMENTAL

AB680

Intervention Type DRUG

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

Zimberelimab

Intervention Type DRUG

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

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Gemcitabine

Intervention Type DRUG

Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Dose Expansion (AB680+zimberelimab+NP/Gem):Cohort A1 (front-line/1L)

Participants with advanced 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

Group Type EXPERIMENTAL

AB680

Intervention Type DRUG

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

Zimberelimab

Intervention Type DRUG

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

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Gemcitabine

Intervention Type DRUG

Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Dose Expansion (AB680 + NP/Gem): Cohort A2 (front-line/1L)

Participants with advanced 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.

Group Type EXPERIMENTAL

AB680

Intervention Type DRUG

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

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Gemcitabine

Intervention Type DRUG

Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

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.

Group Type EXPERIMENTAL

AB680

Intervention Type DRUG

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

Zimberelimab

Intervention Type DRUG

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

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Gemcitabine

Intervention Type DRUG

Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Dose Expansion (AB680 + zimberelimab + NP/Gem): Cohort C (front-line/1L)

Participants with advanced pancreatic cancer naïve to any prior treatment will receive AB680 combined with zimberelimab and NP-Gem chemotherapy regimen.

Group Type EXPERIMENTAL

AB680

Intervention Type DRUG

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

Zimberelimab

Intervention Type DRUG

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

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Gemcitabine

Intervention Type DRUG

Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Dose Expansion (AB680 + NP/Gem): Cohort D (front-line/1L)

Participants with advanced pancreatic cancer naïve to any prior treatment will receive AB680 combined with NP-Gem chemotherapy regimen.

Group Type EXPERIMENTAL

AB680

Intervention Type DRUG

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

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Gemcitabine

Intervention Type DRUG

Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Interventions

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AB680

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

Intervention Type DRUG

Zimberelimab

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

Intervention Type DRUG

Nab-paclitaxel

Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Intervention Type DRUG

Gemcitabine

Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Intervention Type DRUG

Other Intervention Names

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AB122 Abraxane Gemzar

Eligibility Criteria

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Inclusion Criteria

* Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma
* Naïve to any prior treatment, including chemotherapy, biological therapy, or targeted therapy for metastatic disease

* 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
* 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
* 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
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
* Confirmation that an archival tissue sample is available; if not, a new biopsy of a tumor must be obtained
* Prior radiation therapy for metastatic disease must have been completed
* 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
* 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
* 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
* Adequate organ and marrow function

Exclusion Criteria

* Significant cardiovascular disease (NYHA Class III-IV), myocardial infarction or cerebrovascular accident within 12 months of the first dose of investigational agent or history of arterial thromboembolic event, uncontrolled hypertension, unstable arrhythmia, or unstable angina within 3 months or venous thromboses within 1 month of the first dose of investigational agent.
* 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
* 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
* 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
* Has not recovered (ie, ≤ Grade 1 or baseline) from a non-hematologic AEs due to a previously administered agent, except ≤ Grade 2 alopecia or ≤ Grade 2 neuropathy.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Arcus Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Arcus Biosciences, Inc.

Locations

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The Angeles Clinic

Los Angeles, California, United States

Site Status

UCLA Hematology Oncology

Santa Monica, California, United States

Site Status

Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Mid-Florida Hematology & Oncology Centers, PA

Orange City, Florida, United States

Site Status

BRCR Global

Plantation, Florida, United States

Site Status

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, United States

Site Status

NYU Cancer Institute

New York, New York, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Sarah Canon Research Institute

Nashville, Tennessee, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

START San Antonio

San Antonio, Texas, United States

Site Status

Medical Oncology Associates

Spokane, Washington, United States

Site Status

UW Health - UW Carbone Cancer Center - Medical Oncology Clinic

Madison, Wisconsin, United States

Site Status

Countries

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United States

Related Links

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Other Identifiers

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ARC-8 (AB680CSP0002)

Identifier Type: -

Identifier Source: org_study_id

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