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

Advanced Pancreatic Cancer Clinical Trial

— ARC-8  

Official title:

A Phase 1 Study to Evaluate the Safety and Tolerability of AB680 Combination Therapy in Participants With Gastrointestinal Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04104672
• Other study ID #: ARC-8 (AB680CSP0002)
• Status: Recruiting
• Phase: Phase 1
• Start date: November 6, 2019
• Est. completion date: May 2027

Study information

• Verified date: May 2024
• Source: Arcus Biosciences, Inc.
• Contact: Medical Director
• Phone: 1-888-44-ARCUS
• Email: ClinicalTrials[@]arcusbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 195
• Est. completion date: May 2027
• Est. primary completion date: May 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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

Key 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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Advanced Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• AB680
AB680 is a Cluster of Differentiation (CD)73 Inhibitor.
• Zimberelimab
Zimberelimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1.
• Nab-paclitaxel
Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
• Gemcitabine
Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Locations

Country	Name	City	State
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	The Angeles Clinic	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Sarah Canon Research Institute	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYU Cancer Institute	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Mid-Florida Hematology & Oncology Centers, PA	Orange City	Florida
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	BRCR Global	Plantation	Florida
United States	Washington University School of Medicine - Siteman Cancer Center	Saint Louis	Missouri
United States	START Mountain Region - South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas
United States	UCLA Hematology Oncology	Santa Monica	California
United States	Medical Oncology Associates	Spokane	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Arcus Biosciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Number of Participants With Dose Limiting Toxicities		From First dose to day 28
Secondary	Duration of response	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	Start date of response to first progression/death, up to 1 year
Secondary	Disease control rate	Number of participants with complete response, partial response, or stable disease for greater than 6 months per RECIST v1.1	First dose date to first progression/death, up to 1 year
Secondary	Overall survival	Overall survival rate, defined as time between first dose date and date of death	First dose date to date of death, up to 1 year
Secondary	Progression free survival	Number of participants without disease progression per RECIST v1.1	First dose date to first progression/death, up to 1 year
Secondary	AB680 peak plasma concentration (Cmax)	Peak plasma concentration (Cmax) of AB680	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
Secondary	Zimberelimab peak plasma concentration (Cmax)	Peak plasma concentration (Cmax) of Zimberelimab	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
Secondary	AB680 time of peak concentration (Tmax)	Time of peak concentration (Tmax) of AB680	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
Secondary	Zimberelimab time of peak concentration (Tmax)	Time of peak concentration of Zimberelimab	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
Secondary	AB680 area under the plasma concentration versus time curve (AUC)	Area under the plasma concentration versus time curve (AUC) of AB680	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
Secondary	Zimberelimab area under the plasma concentration versus time curve (AUC)	Area under the plasma concentration versus time curve (AUC) of Zimberelimab	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
Secondary	Immunogenicity indicators: anti-drug antibodies (ADA)	Number of participants who develop anti-drug antibodies to Zimberelimab	Day 1, day 15, day 29, day 57, day 85, day 197, day 309, and day 421
Secondary	Overall response rate	Number of Participants with Complete or Partial Response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.1	First dose date to progression or last tumor assessment, up to 1 year