The combination of Array BioPharma‘s immunotherapy ARRY-382 and Keytruda (pembrolizumab) has a manageable safety profile and has shown preliminary signs of effectiveness in pancreatic and ovarian cancer patients, a new Phase 1b study shows.
The findings were recently presented at the Society for Immunotherapy of Cancer’s (SITC) 32nd Annual Meeting in National Harbor, Maryland, in a poster titled, “Phase 1b/2 dose‐escalation study of ARRY‐382, an oral inhibitor of colony‐stimulating factor‐1 receptor (CSF1R), in combination with pembrolizumab for treatment of patients with advanced solid tumors.”
ARRY-382 is an oral colony-stimulating factor 1 receptor (CSF1R) inhibitor. Because this receptor is needed for the immunosuppressive function of tumor-associated macrophages (TAMs), ARRY-382 is expected to enhance T-cell responses against tumor cells.
Also, combining this drug with other immunotherapies that boost immune responses through different approaches may help improve patient outcomes. In preclinical studies, ARRY-382 had better responses when combined with a PD-1 inhibitor.
The Phase 1b/2 trial (NCT02880371) was designed to test the safety, tolerability, and effectiveness of ARRY-382 in combination with Merck‘s PD-1 inhibitor, Keytruda.
The study will be conducted in three parts. In the Phase 1b part, which is already completed, patients received escalating doses of ARRY-382 plus the approved Keytruda regimen to determine the best dose to be used in following trials.
This part included 19 patients, including six with pancreatic cancer, five with colorectal cancer, three with ovarian cancer, two with gastric cancer, two with melanoma, and one with triple-negative breast cancer. Half of the patients had received more than two prior lines of therapy, and 42% had received more than three.
The combination showed a manageable safety profile, with the most common side effects being rash, anemia, and high levels of liver enzymes. Only one patient discontinued treatment due to pneumonitis.
In addition, two patients — one with advanced pancreatic cancer and one with metastatic ovarian cancer — saw a significant reduction in their tumors.
Now, the study is moving into its Phase 2 part, which will continue to test the recommended Phase 2 dose of ARRY-382 in melanoma and non-small cell lung cancer patients. Also, based on the Phase 1 findings, the company is planning to include other patient populations, including a cohort of pancreatic cancer patients.
“We are pleased to announce completion of the Phase 1b clinical study of ARRY-382 in combination with Keytruda,” Ron Squarer, CEO of Array BioPharma, said in a press release. “In addition to establishing an appropriate Phase 2 dose for the combination, we are encouraged by the early signs of activity in patients with tumor types that have been historically unresponsive to anti-PD1 therapies.”