Open Label, Single Arm, Phase 1b/2 Study to Evaluate the Safety and Efficacy of Grapiprant (ARY-007) in Combination With Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 Non-Small Cell Lung Cancer (NSCLC) Adenocarcinoma

Arrys Therapeutics6 sites in 1 country18 target enrollmentJanuary 8, 2019

ConditionsNon-small Cell Lung Cancer Adenocarcinoma

Interventionsgrapiprant and pembrolizumab

Drugsgrapiprant and pembrolizumab

Overview

Phase: Phase 1
Intervention: grapiprant and pembrolizumab
Conditions: Non-small Cell Lung Cancer Adenocarcinoma
Sponsor: Arrys Therapeutics
Enrollment: 18
Locations: 6
Primary Endpoint: Safety and tolerability of grapiprant in combination with pembrolizumab
Status: Terminated
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

January 8, 2019

End Date

February 15, 2021

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Arrys Therapeutics

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male and female adult patients at least 18 years of age on day of signing informed consent
•Histologically confirmed non-small cell lung cancer (NSCLC) adenocarcinoma
•Advanced (stage IIIb) disease that is not amenable to curative intent treatment with concurrent chemoradiation and metastatic (stage IV) patients
•Progressed clinically and/or radiographically per RECIST v1.1 after receiving a PD-1 or PD-L1 antagonist for a minimum of 12 weeks
•Measurable disease per RECIST v1.1
•Disease that can be safely accessed via bronchoscopic, thoracoscopic or percutaneous biopsy for multiple core biopsies and participant is willing to provide tissue from newly obtain biopsies on study in a subgroup of patients
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
•Adequate organ function
•Highly effective birth control
•Able to swallow and absorb oral tablets

Exclusion Criteria

•Current use of NSAIDs, COX-2 inhibitors
•Known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS gene alteration
•No history of smoking (≤100 cigarettes lifetime)
•History of severe hypersensitivity reactions to a PD-1/L1 antibody
•Received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment or 5 half-lives, whichever is shorter
•Received prior radiotherapy within 2 weeks of start of study treatment
•Has received a live vaccine within 30 days prior to the first dose of study treatment
•Taking strong CYP3A4 or P-glycoprotein inhibitors or inducers
•Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
•Known additional malignancy that is progressing or has required active treatment within the past 3 years (with some permitted exceptions)

Arms & Interventions

grapiprant and pembrolizumab combination

Participants will be treated with grapiprant in combination with pembrolizumab.

Intervention: grapiprant and pembrolizumab

Outcomes

Primary Outcomes

Safety and tolerability of grapiprant in combination with pembrolizumab

Time Frame: Up to 90 days after the end of treatment (average of 7 months)

Number of incidence, severity, relationship, concomitant medications administered, and duration of treatment emergent adverse events using CTCAE v5.0

Define the recommended phase 2 dose (RP2D) of grapiprant combined with pembrolizumab

Time Frame: Through Cycle 1 (21 days)

Number, incidence and severity of treatment related adverse events as assessed by CTCAE 5.0

Objective response rate (ORR)

Time Frame: 7 months

Proportion of participants who achieved PR or better during the study per RECIST 1.1 and iRECIST

Secondary Outcomes

Progression-free survival (PFS)(Up to 12 months)
Overall survival (OS)(Up to 2 years from start of study drug)
Duration of treatment (DoT)(7 months)
Disease control rate (DCR)(7 months)
Duration of response (DoR)(Up to 12 months)
PK of grapiprant: AUC(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(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)(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)(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(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(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(Predose through cycle 3 (each cycle is 21 days))