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

NCT03696212 | Terminated Phase 1 FDA Drug

• 2 other identifiers: ARYS-002KEYNOTE-888
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 6

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.

Conditions

Non-small Cell Lung Cancer Adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• 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)

• 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)

• Objective response rate (ORR)

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

  7 months

Secondary Outcomes (12)

• 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

Study Arms (1)

grapiprant and pembrolizumab combination

EXPERIMENTAL

Participants will be treated with grapiprant in combination with pembrolizumab.

Drug: grapiprant and pembrolizumab

Interventions

grapiprant and pembrolizumab DRUG

Participants will be administered 21-day cycles of oral grapiprant in combination with IV pembrolizumab

Also known as: ARYS-007, MK-3475, KEYNOTE-888, IK-007

grapiprant and pembrolizumab combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arrys Therapeutics: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (6)

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Interventions

grapiprant; pembrolizumab

Study Officials

• Jason Sager, MD

  Arrys Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2018
• First Posted: October 4, 2018
• Study Start: January 8, 2019
• Primary Completion: February 15, 2021
• Study Completion: February 15, 2021
• Last Updated: February 21, 2021

Record last verified: 2021-02

Locations

US (6)