Clinical trial NCT03696212: Grapiprant (ARY-007) and Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 NSCLC Adenocarcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer Adenocarcinoma
Lead sponsor: Arrys Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2018-10-04
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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

Key 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)
* Known active CNS metastases and/or carcinomatous meningitis
* Active autoimmune disease that has required systemic treatment in past 2 years
* History of pneumonitis that required steroids or has current pneumonitis
* Has an active infection requiring systemic therapy
* Recent or current GI ulcer, colitis or non-immune colitis
* Known history of human immunodeficiency virus (HIV) infection, or known active Hepatitis B, or Hepatitis C virus infection
* Has had an allogeneic tissue/solid organ transplant
* Clinically significant (i.e.active) cardiovascular disease

Primary outcomes:
measure: Safety and tolerability of grapiprant in combination with pembrolizumab
timeFrame: Up to 90 days after the end of treatment (average of 7 months)
measure: Define the recommended phase 2 dose (RP2D) of grapiprant combined with pembrolizumab
timeFrame: Through Cycle 1 (21 days)
measure: Objective response rate (ORR)
timeFrame: 7 months
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 12 months
measure: Overall survival (OS)
timeFrame: Up to 2 years from start of study drug
measure: Duration of treatment (DoT)
timeFrame: 7 months
measure: Disease control rate (DCR)
timeFrame: 7 months
measure: Duration of response (DoR)
timeFrame: Up to 12 months
measure: PK of grapiprant: AUC
timeFrame: 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).
measure: PK of grapiprant: Cmax
timeFrame: 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).
measure: Plasma decay half-life (t1/2)
timeFrame: 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).
measure: Apparent oral clearance (CL/F)
timeFrame: 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).
measure: Peak to trough ratio
timeFrame: 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).
measure: Observed accumulation ratio
timeFrame: 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).
measure: Pharmacodynamic immune effects in paired tumor biopsies
timeFrame: Predose through cycle 3 (each cycle is 21 days)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
Study officials:
affiliation: Arrys Therapeutics
name: Jason Sager, MD
role: STUDY_DIRECTOR
References: