This study will evaluate the safety and tolerability of epacadostat (INCB024360) administered in combination with atezolizumab (MPDL3280A) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that have been previously treated with platinum-based chemotherapy and Stage IV urothelial carcinoma who have failed a platinum-based chemotherapy regimen. The study will be conducted in two phases. The dose escalation phase will utilize a 3 + 3 design to identify the maximum tolerated dose (MTD) or a Pharmacologically Active Dose (PAD) of the combination. This will be followed by a dose expansion phase, which will be comprised of three cohorts. Expansion Cohorts 1 \& 2 will further evaluate the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics at the dose identified in phase one. Expansion Cohort 3 will evaluate the change in biomarker expression following treatment with epacadostat as monotherapy followed by epacadostat and atezolizumab administered in combination.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
atezolizumab: administered intravenously (IV) every three weeks (q3w)
epacadostat: Oral daily dosing
Pinnacle Oncology Hematology
Scottsdale, Arizona, United States
Yale University
New Haven, Connecticut, United States
Harvard-Mass General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
University of Washington
Seattle, Washington, United States
Incidence of adverse events (AEs)
Time frame: Continuously for duration of study participation and up to 42 days after the last dose [approximately 8 months
Incidence of dose-limiting toxicities (DLTs)
Time frame: 21 days following the first administration of atezolizumab and epacadostat
Objective response rate (ORR)
ORR determined by radiographic disease assessments per modified RECIST v1.1
Time frame: Measured every 6 weeks for duration of study participation [approximately 8 months]
Durability of response
Time from the earliest date of disease response until earliest date of disease progression based on modified RECIST v1.1
Time frame: Measured every 6 weeks for duration of study participation [approximately 8 months]
Progression-free survival
Time from date of enrollment until the earliest date of disease progression per modified RECIST v1.1 or death due to any cause, whichever is earlier.
Time frame: Measured every 6 weeks for duration of study participation [approximately 8 months]
Duration of disease control
Time from first dose until report of disease progression for subjects who reported stable disease or better based on modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: Measured every 6 weeks for duration of study participation [approximately 8 months]
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