Grapiprant (ARY-007) and Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 NSCLC Adenocarcinoma
- Conditions
- Non-small Cell Lung Cancer Adenocarcinoma
- Interventions
- Registration Number
- NCT03696212
- Lead Sponsor
- Arrys Therapeutics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 18
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description grapiprant and pembrolizumab combination grapiprant and pembrolizumab Participants will be treated with grapiprant in combination with pembrolizumab.
- Primary Outcome Measures
Name Time Method Safety and tolerability of grapiprant in combination with pembrolizumab 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 Through Cycle 1 (21 days) Number, incidence and severity of treatment related adverse events as assessed by CTCAE 5.0
Objective response rate (ORR) 7 months Proportion of participants who achieved PR or better during the study per RECIST 1.1 and iRECIST
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) Up to 12 months Participants who discontinue treatment without disease progression
Overall survival (OS) Up to 2 years from start of study drug Date of study drug to date of death due to any cause
Duration of treatment (DoT) 7 months Disease response for time of duration on treatment
Disease control rate (DCR) 7 months Percentage of patients who have achieved CR, PR and stable disease
Duration of response (DoR) Up to 12 months Time from documentation of tumor response to disease progression per RECIST and iRECIST 1.1
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). Area under the plasma concentration-time curve
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). Peak serum concentration of grapiprant
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). Measurement of half-life of grapiprant after dosing
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). Rate of elimination of the drug from plasma after oral administration
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). Measure how drug effect is sustained over dose interval
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). Relationship between the dosing interval and the rate of elimination for the drug
Pharmacodynamic immune effects in paired tumor biopsies Predose through cycle 3 (each cycle is 21 days) Asses changes in tumor infiltrating helper T cells, cytoxic T cells and regulatory monocyte/macrophages with study treatment
Trial Locations
- Locations (6)
Stanford University Medical Center
🇺🇸Stanford, California, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
University of Pennsylvania Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States