Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Single Agent run-in with grapiprant and then combination treatment of grapiprant and pembrolizumab.

Participants will be treated with grapiprant in combination with pembrolizumab.

Cohort 1 will be treated for 1 week with oral grapiprant as a single agent, followed by 21-day combination treatment cycles of oral grapiprant in combination with IV pembrolizumab.

grapiprant

Cohort 2 will be administered 21-day combination treatment cycles of oral grapiprant in combination with IV pembrolizumab.

grapiprant and pembrolizumab

Sergio Santillana, MD

This study will be conducted in adult participants diagnosed with any form of an advanced or progressive MSS CRC for which 1st and 2nd line standard therapy (at least one of which contained fluorouracil) is no longer effective or is intolerable. This is a phase 1b, 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 and characterize the PK of grapiprant alone and in combination with pembrolizumab. Disease response, pharmacodynamics, and response biomarkers will also be assessed.

Grapiprant and Pembrolizumab in Patients With Advanced or Progressive MSS Colorectal Cancer

An Open-label, Single-arm, Phase 1b Study to Evaluate the Safety and Efficacy of Grapiprant (ARY-007) in Combination With Pembolizumab in Patients With Advanced or Progressive Microsatellite Stable (MSS) Colorectal Cancer (CRC)

Number of incidence, severity, and duration of treatment emergent adverse events using CTCAE v5.0

Number, incidence and severity of treatment related adverse events as assessed by CTCAE 5.0

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

Time when criteria for response are met, to the first documentation of relapse or progression

Participants who discontinue treatment without disease progression

Percentage of participants who achieved a CR, PR and stable disease

Date of study drug to date of death due to any cause. If no documentation of death at time of the analysis will be censored as of the date last known to be alive, or the data cutoff date, whichever is earlier.

Assess changes in serum tumor markers including but not limited to carcinoembryonic antigen (CEA), when appropriate (eg. CA-19.9, CA125, and lactate dehyrogenase (LDH)) with disease response.

Assess changes in tumor infiltrating helper T cells, cytotoxic T cells and regulatory monocyte/macrophages with study drug treatment

Evaluate disease response in all evaluable participants and in those with a positive initial assessment of Urine prostaglandin E2 metabolite (PGEM)

First time to reach maximum \[peak\] observed plasma concentration

Area under the plasma concentration time curve from time 0 to the end of the dosing interval (AUC0 last)

Measurement of half-life of grapiprant after dosing

Rate of elimination of the drug from plasma after oral administration

Measure how drug effect is sustained over dose interval

Relationship between the dosing interval and the rate of elimination for the drug.

Merck Sharp & Dohme LLC

Arrys Therapeutics

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Adenocarcinoma

Carcinoma

Adenocarcinoma of Lung

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Lung Adenocarcinoma

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

Jason Sager, MD

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.

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

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

Number of incidence, severity, relationship, concomitant medications administered, and duration of treatment emergent adverse events using CTCAE v5.0

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

Date of study drug to date of death due to any cause

Disease response for time of duration on treatment

Percentage of patients who have achieved CR, PR and stable disease

Time from documentation of tumor response to disease progression per RECIST and iRECIST 1.1

Area under the plasma concentration-time curve

Relationship between the dosing interval and the rate of elimination for the drug

Asses changes in tumor infiltrating helper T cells, cytoxic T cells and regulatory monocyte/macrophages with study treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Grapiprant and Pembrolizumab in Patients With Advanced or Progressive MSS Colorectal Cancer	NCT03658772	Microsatellite ...	grapiprant grapiprant and ...	18 Years -	Arrys Therapeutics
Grapiprant (ARY-007) and Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 NSCLC Adenocarcinoma	NCT03696212	Non-small Cell ...	grapiprant and ...	18 Years -	Arrys Therapeutics

Spots Global Cancer Trial Database for grapiprant and pembrolizumab