Advanced Pancreatic Cancer
Conditions
Keywords
AB680, Zimberelimab, Pancreatic cancer
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.
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.
Interventions
DRUGAB680
AB680 is a Cluster of Differentiation (CD)73 Inhibitor.
DRUGZimberelimab
Zimberelimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1.
DRUGNab-paclitaxel
Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
DRUGGemcitabine
Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
Sponsors
Arcus Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
3+3 Dose escalation design
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Number of Participants With Dose Limiting Toxicities | From First dose to day 28 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Disease control rate | First dose date to first progression/death | Number of participants with complete response, partial response, or stable disease for greater than 6 months per RECIST v1.1 |
| 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 |
| Progression free survival | First dose date to first progression/death | Number of participants without disease progression per RECIST v1.1 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
United States
Contacts
STUDY_DIRECTORMedical Director
Arcus Biosciences, Inc.
Outcome results
None listed