This study will be conducted in adult participants diagnosed with NSCLC who have been previously treated for a minimum of 12 weeks with any PD-1 or PD-L1 checkpoint inhibitor. This is a phase 1b/2, multi-center, open label study designed to assess safety and tolerability of grapiprant in combination with pembrolizumab, to determine the recommended phase 2 dose (RP2D) with pembrolizumab, and to evaluate disease response with grapiprant based on investigator assessments. Pharmacokinetics, pharmacodynamics and response biomarkers will also be assessed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Participants will be administered 21-day cycles of oral grapiprant in combination with IV pembrolizumab
Stanford University Medical Center
Stanford, California, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
START Midwest
Grand Rapids, Michigan, United States
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Virginia Cancer Specialists
Fairfax, Virginia, United States
Safety and tolerability of grapiprant in combination with pembrolizumab
Number of incidence, severity, relationship, concomitant medications administered, and duration of treatment emergent adverse events using CTCAE v5.0
Time frame: Up to 90 days after the end of treatment (average of 7 months)
Define the recommended phase 2 dose (RP2D) of grapiprant combined with pembrolizumab
Number, incidence and severity of treatment related adverse events as assessed by CTCAE 5.0
Time frame: Through Cycle 1 (21 days)
Objective response rate (ORR)
Proportion of participants who achieved PR or better during the study per RECIST 1.1 and iRECIST
Time frame: 7 months
Progression-free survival (PFS)
Participants who discontinue treatment without disease progression
Time frame: Up to 12 months
Overall survival (OS)
Date of study drug to date of death due to any cause
Time frame: Up to 2 years from start of study drug
Duration of treatment (DoT)
Disease response for time of duration on treatment
Time frame: 7 months
Disease control rate (DCR)
Percentage of patients who have achieved CR, PR and stable disease
Time frame: 7 months
Duration of response (DoR)
Time from documentation of tumor response to disease progression per RECIST and iRECIST 1.1
Time frame: Up to 12 months
PK of grapiprant: AUC
Area under the plasma concentration-time curve
Time frame: Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with Cycle 4 (every 42 days) through end of treatment (average of 4 months).
PK of grapiprant: Cmax
Peak serum concentration of grapiprant
Time frame: Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with Cycle 4 (every 42 days) through end of treatment (average of 4 months).
Plasma decay half-life (t1/2)
Measurement of half-life of grapiprant after dosing
Time frame: Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with Cycle 4 (every 42 days) through end of treatment (average of 4 months).
Apparent oral clearance (CL/F)
Rate of elimination of the drug from plasma after oral administration
Time frame: Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with Cycle 4 (every 42 days) through end of treatment (average of 4 months).
Peak to trough ratio
Measure how drug effect is sustained over dose interval
Time frame: Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with Cycle 4 (every 42 days) through end of treatment (average of 4 months).
Observed accumulation ratio
Relationship between the dosing interval and the rate of elimination for the drug
Time frame: Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with Cycle 4 (every 42 days) through end of treatment (average of 4 months).
Pharmacodynamic immune effects in paired tumor biopsies
Asses changes in tumor infiltrating helper T cells, cytoxic T cells and regulatory monocyte/macrophages with study treatment
Time frame: Predose through cycle 3 (each cycle is 21 days)
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