A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies
ARC-8
A Phase 1 Study to Evaluate the Safety and Tolerability of AB680 Combination Therapy in Participants With Gastrointestinal Malignancies
1 other identifier
interventional
196
1 country
13
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2019
Longer than P75 for phase_1
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 23, 2019
CompletedFirst Posted
Study publicly available on registry
September 26, 2019
CompletedStudy Start
First participant enrolled
November 6, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 1, 2027
May 7, 2026
May 1, 2026
7.5 years
September 23, 2019
May 5, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of participants with Treatment Emergent Adverse Events (TEAEs)
Safety will be assessed by monitoring adverse events and clinically relevant changes in 12 lead Electrocardiogram (ECG) and Physical examination findings
From first dose date to 90 days after the last dose (approximately 1 year)
Number of Participants With Dose Limiting Toxicities
From First dose to day 28
Secondary Outcomes (12)
Duration of response
Start date of response to first progression/death, up to 1 year
Disease control rate
First dose date to first progression/death
Overall survival
First dose date to date of death, up to 1 year
Progression free survival
First dose date to first progression/death
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
- +7 more secondary outcomes
Study Arms (7)
Dose Escalation
EXPERIMENTALDose 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.
Dose Expansion (AB680+zimberelimab+ NP/Gem): Cohort A (front-line/1L)
EXPERIMENTALParticipants 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
Dose Expansion (AB680+zimberelimab+NP/Gem):Cohort A1 (front-line/1L)
EXPERIMENTALParticipants 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
Dose Expansion (AB680 + NP/Gem): Cohort A2 (front-line/1L)
EXPERIMENTALParticipants 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.
Dose Expansion (AB680 + zimberelimab + NP/Gem): Cohort B (second-line/2L)
EXPERIMENTALParticipants 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.
Dose Expansion (AB680 + zimberelimab + NP/Gem): Cohort C (front-line/1L)
EXPERIMENTALParticipants with advanced pancreatic cancer naïve to any prior treatment will receive AB680 combined with zimberelimab and NP-Gem chemotherapy regimen.
Dose Expansion (AB680 + NP/Gem): Cohort D (front-line/1L)
EXPERIMENTALParticipants with advanced pancreatic cancer naïve to any prior treatment will receive AB680 combined with NP-Gem chemotherapy regimen.
Interventions
AB680 is a Cluster of Differentiation (CD)73 Inhibitor.
Zimberelimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1.
Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
Research Site
Los Angeles, California, 90025, United States
Research Site
Santa Monica, California, 90404, United States
Research Site
St Louis, Missouri, 63110, United States
Research Site
New York, New York, 10016, United States
Research Site
New York, New York, 10032, United States
Research Site
New York, New York, 10065, United States
Research Site
Oklahoma City, Oklahoma, 73104, United States
Research Site
Philadelphia, Pennsylvania, 19104, United States
Research Site
Pittsburgh, Pennsylvania, 15232, United States
Research Site
Nashville, Tennessee, 37203, United States
Research Site
Houston, Texas, 77030, United States
Research Site
San Antonio, Texas, 78229, United States
Research Site
Madison, Wisconsin, 53792, United States
Related Publications (1)
Wainberg ZA, Manji GA, Bahary N, Ulahannan SV, Pant S, Spigel DR, Uboha NV, Oberstein PE, Saeed A, Beagle B, Kim JY, Wang N, Weeder B, Shitole S, Mrouj K, Scott JR, Ensign LG, DiRenzo DM, Walters MJ, Wu W, Kaplan A, Cho S, Kabbarah O, O'Reilly EM. Quemliclustat and chemotherapy with or without zimberelimab in metastatic pancreatic adenocarcinoma: a randomized phase 1 trial. Nat Med. 2026 Apr;32(4):1267-1277. doi: 10.1038/s41591-026-04283-z. Epub 2026 Mar 30.
PMID: 41912809DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Arcus Biosciences, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 23, 2019
First Posted
September 26, 2019
Study Start
November 6, 2019
Primary Completion (Estimated)
May 1, 2027
Study Completion (Estimated)
May 1, 2027
Last Updated
May 7, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
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. For more information, please visit our website.