Phase II Trial of Pembrolizumab (MK-3475) With GM-CSF Induction in Advanced Biliary Cancers
Overview
- Phase
- Phase 2
- Intervention
- Sargramostim
- Conditions
- Biliary Cancer
- Sponsor
- Robin Kate Kelley
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- Overall Response Rate (ORR)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This is an open label phase II trial to examine efficacy and safety of a novel combination of pembrolizumab plus induction GM-CSF in patients with advanced biliary cancers treated at University of California, San Francisco (UCSF).
This phase II study will examine the efficacy and safety of the novel combination of pembrolizumab plus induction GM-CSF in advanced biliary cancer patients with the hypotheses that the combination may increase proportion of patients with overall response compared to contemporary historical controls, with acceptable safety.
Investigators
Robin Kate Kelley
Associate Professor
University of California, San Francisco
Eligibility Criteria
Inclusion Criteria
- •Be willing and able to provide written informed consent for the trial.
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- •Demonstrate adequate organ function
- •Absolute neutrophil count (ANC) \>= 1,000/microliter (mcL)(performed within 28 days of treatment initiation)
- •Platelets \>= 60,000/mcL (\>= 75,000/mcL in expansion cohort) (performed within 28 days of treatment initiation)
- •Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 28 days of treatment initiation)
- •Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)) \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (performed within 28 days of treatment initiation)
- •Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN (performed within 28 days of treatment initiation)
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =\< 5 X ULN (performed within 28 days of treatment initiation)
- •Albumin \>= 2.5 mg/dL (performed within 28 days of treatment initiation)
Exclusion Criteria
- •Is currently participating and receiving study therapy or has participated and received study therapy in a study of an investigational agent, or used an investigational device within 4 weeks of the first dose of treatment.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy for purposes of immunosuppression or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- •Has a known history of active Bacillus Tuberculosis (TB).
- •Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- •Has untreated active Hepatitis B (e.g., HBsAg reactive).
- •Has an active infection requiring systemic antibiotic therapy at time of enrollment.
- •Treatment with antibiotic prophylaxis for indwelling biliary stent(s) or peri-procedural antibiotics for uncomplicated biliary stent exchanges is allowed and not an exclusion
- •Hypersensitivity to pembrolizumab or any of its excipients.
- •Has received treatment with an anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- •Has received treatment with chemotherapy, targeted small molecule therapy, or radiation therapy to non-liver sites within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent administered more than 2 weeks earlier.
Arms & Interventions
Pembrolizumab and GM-CSF
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
Intervention: Sargramostim
Pembrolizumab and GM-CSF
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Overall Response Rate (ORR)
Time Frame: Up to 2 years
Proportion of subjects with measurable disease at study entry who obtained either a complete response (CR) or partial response (PR) (confirmed + unconfirmed) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at any time during the course of treatment.
Secondary Outcomes
- Proportion of Participants With Treatment-related AEs(During study treatment and for 30 days after last dose or until start of new treatment (up to 2 years))
- Median Overall Survival (OS)(Within 4 years after start of treatment)
- Proportion of Participants With PD-L1 Positive Status(Up to 4 years)
- Median Duration of Response Stratified by Sub-type of Biliary Cancer(Within 4 years after start of study treatment)
- Median Progression Free-Survival (PFS)(Within 4 years after start of study treatment)
- Median PFS Stratified by Sub-type of Biliary Cancer(Within 4 years after start of study treatment)
- Median Overall Survival (OS) Stratified by Sub-type of Biliary Cancer(Within 4 years after start of treatment)
- Proportion of Participants With Progression-Free Survival (PFS) at 6 Months(6 months after start of study treatment)
- Median Duration of Response(Within 4 years after start of study treatment)