ARRY-382 / CSF1R

Target: CSF1R | Disease State: Cancer

Program Description

In July 2016, Array initiated a Phase 1/2 dose escalation immuno-oncology trial of ARRY-382 in combination with pembrolizumab (Keytruda®), a Programmed Cell Death Receptor 1 (PD-1) antibody, in patients with advanced solid tumors. ARRY-382 is a wholly-owned, potent, highly selective, small molecule inhibitor of CSF-1R kinase activity.

The study will enroll up to 18 patients with selected advanced solid tumors to determine the maximum tolerated dose and/or recommended Phase 2 dose of the combination. In addition, the safety profile, pharmacodynamic effects, and preliminary assessment of activity of the combination will be assessed. Array is advancing the combination into expansion cohorts of patients with pancreatic cancer, ovarian cancer and other solid tumors.

As presented at the Society for Immunotherapy of Cancer (SITC) 32nd Annual Meeting, in the Phase 1b dose escalation trial, the recommended Phase 2 dose of ARRY-382 was determined to be 300 mg daily in combination with KEYTRUDA 2 mg/kg given intravenously every 3 weeks.

Nineteen patients, with a median of two prior lines of therapy and 42% with ≥3 prior regimens, were treated in the study. Patients with pancreatic (n=6), colorectal (n=5), ovarian (n=3), gastric and melanoma (n=2, each), and triple negative breast cancer (n=1) were enrolled. Investigators noted that ARRY-382 had a manageable safety profile when administered with KEYTRUDA in this study, and the most common grade 3/4 adverse events (AEs) (>10%), regardless of causality, included increased AST, increased blood creatine kinase (CK), rash, increased lipase, increased alkaline phosphatase (ALP), increased alanine aminotransferase (ALT) and anemia.

The combination of ARRY-382 and KEYTRUDA demonstrated early signs of activity, with 11% (n=2) of patients achieving a confirmed partial response, based on RECIST version 1.1 guidelines. The first responder, who was treated with ARRY-382 at 200 mg, had Stage III pancreatic ductal adenocarcinoma. As of the data cut-off, this patient was on study treatment in cycle 14 (42 weeks). The second responder, who was treated with ARRY-382 at 300 mg, had stage IV ovarian cancer with liver metastasis. As of the data cut-off, this patient was on study treatment in cycle 8 (24 weeks).

Results from a prior Phase 1 study designed to assess the safety, pharmacokinetics and pharmacodynamics of ARRY-382 for treating patients with cancer have been presented and a dose and schedule that demonstrates target engagement based on multiple pharmacodynamic biomarkers was identified for further study. 

Clinical Trials

Trial Data
Trial Title
Program: ARRY-382
Phase: 2
Status: Recruiting
Disease: Solid tumors
Sponsor: Array BioPharma
Trial Information: NCT02880371
Trial Title: A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of Patients With Advanced Solid Tumors

To learn more about ARRY-382 clinical trials, click here.

Publications and Presentations



Society for Immunotherapy of Cancer (SITC) 32nd Annual Meeting

A phase 1b/2 dose-escalation study of ARRY-382, an oral inhibitor of colony-stimulating factor-1 receptor (CSF-1R) in combination with pembrolizumab for the treatment of patients with advanced solid tumors

Wael A. Harb, et al.



AACR-NCI-EORTC Symposium on Molecular Targets and Cancer Therapeutics

A Phase 1 Study of ARRY-382, an Oral Inhibitor of Colony-stimulating Factor-1 Receptor (CSF1R), in Patients with Advanced or Metastatic Cancers

J. Bendell, et al.

To view all publications, click here.

These compounds and their uses are investigational and have not been approved by the U.S. Food and Drug Administration. This information is presented only for purposes of providing a general overview of our clinical trials.