Non-small Cell Lung Cancer Adenocarcinoma Clinical Trial
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
| Verified date | February 2021 |
| Source | Arrys Therapeutics |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 18 |
| Est. completion date | February 15, 2021 |
| Est. primary completion date | February 15, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | Barbara Ann Karmanos Cancer Institute | Detroit | Michigan |
| United States | Virginia Cancer Specialists | Fairfax | Virginia |
| United States | START Midwest | Grand Rapids | Michigan |
| United States | Fox Chase Cancer Center | Philadelphia | Pennsylvania |
| United States | University of Pennsylvania Abramson Cancer Center | Philadelphia | Pennsylvania |
| United States | Stanford University Medical Center | Stanford | California |
| Lead Sponsor | Collaborator |
|---|---|
| Arrys Therapeutics | Merck Sharp & Dohme Corp. |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Up to 90 days after the end of treatment (average of 7 months) | |
| Primary | 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 | Through Cycle 1 (21 days) | |
| Primary | Objective response rate (ORR) | Proportion of participants who achieved PR or better during the study per RECIST 1.1 and iRECIST | 7 months | |
| Secondary | Progression-free survival (PFS) | Participants who discontinue treatment without disease progression | Up to 12 months | |
| Secondary | Overall survival (OS) | Date of study drug to date of death due to any cause | Up to 2 years from start of study drug | |
| Secondary | Duration of treatment (DoT) | Disease response for time of duration on treatment | 7 months | |
| Secondary | Disease control rate (DCR) | Percentage of patients who have achieved CR, PR and stable disease | 7 months | |
| Secondary | Duration of response (DoR) | Time from documentation of tumor response to disease progression per RECIST and iRECIST 1.1 | Up to 12 months | |
| Secondary | PK of grapiprant: AUC | Area under the plasma concentration-time curve | 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). | |
| Secondary | PK of grapiprant: Cmax | Peak serum concentration of grapiprant | 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). | |
| Secondary | Plasma decay half-life (t1/2) | Measurement of half-life of grapiprant after dosing | 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). | |
| Secondary | Apparent oral clearance (CL/F) | Rate of elimination of the drug from plasma after oral administration | 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). | |
| Secondary | Peak to trough ratio | Measure how drug effect is sustained over dose interval | 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). | |
| Secondary | Observed accumulation ratio | Relationship between the dosing interval and the rate of elimination for the drug | 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). | |
| Secondary | 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 | Predose through cycle 3 (each cycle is 21 days) |