Clinical trial NCT04104672: A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies
Official title: A Phase 1 Study to Evaluate the Safety and Tolerability of AB680 Combination Therapy in Participants With Gastrointestinal Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Pancreatic Cancer
Keywords: AB680
Zimberelimab
Pancreatic cancer
Lead sponsor: Arcus Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2019-09-26
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 3+3 Dose escalation design
Primary purpose: TREATMENT

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.

Eligibility 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/Exclusion criteria may apply.

Primary outcomes:
measure: Number of participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: From first dose date to 90 days after the last dose (approximately 1 year)
measure: Number of Participants With Dose Limiting Toxicities
timeFrame: From First dose to day 28
Secondary outcomes:
measure: Duration of response
timeFrame: Start date of response to first progression/death, up to 1 year
measure: Disease control rate
timeFrame: First dose date to first progression/death
measure: Overall survival
timeFrame: First dose date to date of death, up to 1 year
measure: Progression free survival
timeFrame: First dose date to first progression/death
measure: AB680 peak plasma concentration (Cmax)
timeFrame: 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
measure: Zimberelimab peak plasma concentration (Cmax)
timeFrame: 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
measure: AB680 time of peak concentration (Tmax)
timeFrame: 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
measure: Zimberelimab time of peak concentration (Tmax)
timeFrame: 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
measure: AB680 area under the plasma concentration versus time curve (AUC)
timeFrame: 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
measure: Zimberelimab area under the plasma concentration versus time curve (AUC)
timeFrame: 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
measure: Immunogenicity indicators: anti-drug antibodies (ADA)
timeFrame: Day 1, day 15, day 29, day 57, day 85, day 197, day 309, and day 421
measure: Overall response rate
timeFrame: First dose date to progression or last tumor assessment, up to 1 year
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology Oncology
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Orange City
country: United States
facility: Mid-Florida Hematology & Oncology Centers, PA
state: Florida
city: Plantation
country: United States
facility: BRCR Global
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: New York
country: United States
facility: NYU Cancer Institute
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Canon Research Institute
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: START San Antonio
state: Texas
city: Spokane
country: United States
facility: Medical Oncology Associates
state: Washington
city: Madison
country: United States
facility: UW Health - UW Carbone Cancer Center - Medical Oncology Clinic
state: Wisconsin
Study officials:
affiliation: Arcus Biosciences, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: