A Phase 2, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of GS-5745 Combined With Nivolumab Versus Nivolumab Alone in Subjects With Unresectable or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Gilead Sciences
- Enrollment
- 144
- Primary Endpoint
- Objective Response Rate (ORR)
Overview
Brief Summary
The primary objective of this study is to evaluate and compare the efficacy of andecaliximab (GS-5745) in combination with nivolumab versus nivolumab alone in adults with recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically confirmed inoperable locally advanced or metastatic adenocarcinoma of the stomach or GEJ which have progressed on at least 1 prior systemic therapy or line of treatment for unresectable/metastatic disease
- •Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 1
- •Measurable disease according to Response Criteria in Solid Tumors (RECIST) v1.1
- •Tumor sites that can be accessed for repeat biopsies
- •Archival tumor tissue, preferably obtained from the most recent available biopsy; there must be adequate tissue for a Cochran-Mantel Haenszel (CMH) test stratified by programmed death ligand 1 (PD-L1) stratification test, as assessed by central pathologist
- •Individuals not receiving anticoagulant medication must have an international normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin (aPTT) ≤ 1.5 x upper limit of normal (ULN)
- •Required baseline laboratory data as outlined in protocol
Exclusion Criteria
- •Individuals who have received only neoadjuvant or adjuvant therapy for gastric adenocarcinoma
- •Radiotherapy within 28 days of randomization
- •Uncontrolled intercurrent illness as outlined in protocol
- •History of a concurrent or second malignancy except for those outlined in protocol
- •Major surgery, within 28 days of first dose of study drug
- •Known positive status for human immunodeficiency virus (HIV)
- •Known acute or chronic-active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
- •Chronic daily treatment with oral corticosteroids (dose of \> 10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days of randomization
- •Known or suspected central nervous system metastases
- •Documented myocardial infarction or unstable/uncontrolled cardiac disease within 6 months of randomization
Arms & Interventions
Andecaliximab + Nivolumab
Andecaliximab 800 mg plus nivolumab 3 mg/kg administered every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent (up to 34 weeks at the time of the primary efficacy analysis; up to 101 weeks at the time of the safety follow-up analysis).
Intervention: Andecaliximab (Drug)
Andecaliximab + Nivolumab
Andecaliximab 800 mg plus nivolumab 3 mg/kg administered every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent (up to 34 weeks at the time of the primary efficacy analysis; up to 101 weeks at the time of the safety follow-up analysis).
Intervention: Nivolumab (Drug)
Nivolumab
Nivolumab 3 mg/kg administered every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent (up to 41 weeks at the time of the primary efficacy analysis; up to 97 weeks at the time of the safety follow-up analysis).
Intervention: Nivolumab (Drug)
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: Up to 41 weeks
ORR was defined as the percentage of participants with confirmed overall best response of complete response (CR) or partial response (PR) after starting study drug but before starting any new chemotherapy or radiotherapy as assessed by the investigator according to Response Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Secondary Outcomes
- Progression Free Survival (PFS)(Andecaliximab + Nivolumab median follow-up time: 7.0 months; Nivolumab median follow-up time: 7.1 months)
- Overall Survival (OS)(Andecaliximab + Nivolumab median follow-up time: 7.0 months; Nivolumab median follow-up time: 7.0 months)
- Duration of Response (DOR)(Andecaliximab + Nivolumab median follow-up time: 7.0 months; Nivolumab median follow-up time: 7.1 months)
- Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)(Andecaliximab: First dose date up to last dose (maximum: 101 weeks) + 30 days; Nivolumab: First dose date up to last dose (maximum: 101 weeks) + 5 months)
- Percentage of Participants Who Experienced Treatment-emergent Laboratory Abnormalities(Andecaliximab: First dose date up to last dose (maximum: 101 weeks) + 30 days; Nivolumab: First dose date up to last dose (maximum: 101 weeks) + 5 months)