Clinical Trials /

Grapiprant (ARY-007) and Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 NSCLC Adenocarcinoma

NCT03696212

Description:

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.

Related Conditions:
  • Lung Adenocarcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: ARYS-002
  • NCT ID: NCT03696212

Conditions

  • Non-small Cell Lung Cancer Adenocarcinoma

Interventions

DrugSynonymsArms
grapiprant and pembrolizumabARYS-007, MK-3475, KEYNOTE-888grapiprant and pembrolizumab combination

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
grapiprant and pembrolizumab combinationExperimentalParticipants will be treated with grapiprant in combination with pembrolizumab.
  • grapiprant and pembrolizumab

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

        Key Exclusion Criteria:

          -  Current use of NSAIDs, COX-2 inhibitors

          -  Known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS
             gene alteration, BRAF gene mutation

          -  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

          -  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, Hepatitis B, or active
             Hepatitis C virus infection

          -  Clinically significant (i.e.active) cardiovascular disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of grapiprant in combination with pembrolizumab
Time Frame:Up to 90 days after the end of treatment (average of 7 months)
Safety Issue:
Description:Number of incidence, severity, relationship, concomitant medications administered, and duration of treatment emergent adverse events using CTCAE v5.0

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:Up to 12 months
Safety Issue:
Description:Participants who discontinue treatment without disease progression
Measure:Overall survival (OS)
Time Frame:Up to 2 years from start of study drug
Safety Issue:
Description:Date of study drug to date of death due to any cause
Measure:Duration of treatment (DoT)
Time Frame:7 months
Safety Issue:
Description:Disease response for time of duration on treatment
Measure:Disease control rate (DCR)
Time Frame:7 months
Safety Issue:
Description:Percentage of patients who have achieved CR, PR and stable disease
Measure:Duration of response (DoR)
Time Frame:Up to 12 months
Safety Issue:
Description:Time from documentation of tumor response to disease progression per RECIST and iRECIST 1.1
Measure:PK of grapiprant: AUC
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).
Safety Issue:
Description:Area under the plasma concentration-time curve
Measure:PK of grapiprant: Cmax
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).
Safety Issue:
Description:Peak serum concentration of grapiprant
Measure:Plasma decay half-life (t1/2)
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).
Safety Issue:
Description:Measurement of half-life of grapiprant after dosing
Measure:Apparent oral clearance (CL/F)
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).
Safety Issue:
Description:Rate of elimination of the drug from plasma after oral administration
Measure:Peak to trough ratio
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).
Safety Issue:
Description:Measure how drug effect is sustained over dose interval
Measure:Observed accumulation ratio
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).
Safety Issue:
Description:Relationship between the dosing interval and the rate of elimination for the drug
Measure:Pharmacodynamic immune effects in paired tumor biopsies
Time Frame:Predose through cycle 3 (each cycle is 21 days)
Safety Issue:
Description:Asses changes in tumor infiltrating helper T cells, cytoxic T cells and regulatory monocyte/macrophages with study treatment

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Arrys Therapeutics

Last Updated