An immunotherapy combination that adds the interleukin-10 (IL-10) agonist AM0010 to FOLFOX chemotherapy will be evaluated in a phase III trial for patients with metastatic pancreatic cancer (NCT02923921). AM0010, which is being developed by ARMO BioSciences, is a pegylated form of IL-10, shown to stimulate an immune response by inducing the activation and proliferation of tumor-specific CD8-positive T cells, resulting in an antitumor immune memory.
RATIONALEThe rationale for the trial was established in a phase I dose-escalation study for patients with advanced solid tumors including pancreatic cancer. Antitumor responses were assessed according to immune-related response criteria, and 41 of the 51 enrolled patients (80.4%) were evaluable. Of the 2 evaluable patients with pancreatic cancer, 1 achieved stable disease that lasted 4 months, and both had strong reduction in the tumor marker CA19-9. In an expansion monotherapy cohort of 22 patients with pancreatic cancer treated with AM0010 with a median of 4 prior therapies, 53% had stable disease, 27% had a more than 50% reduction of the tumor marker CA19-9, and the 1-year survival rate was 22%. Early results of a combination of AM0010 and FOLFOX showed encouraging responses.
The most common adverse events are fatigue, anemia, and thrombocytopenia, which are usually manageable, according to Jeffrey R. Infante, MD, director of the Drug Development Program at Sarah Cannon Research Institute in Nashville.
Anemia and thrombocytopenia are also common with cytotoxic chemotherapy; the protocol for the phase III trial is set up to help clinicians manage the toxicities, with flexibility around dose reductions and the ability to hold medications until the patient has recovered. The effect from AM0010 is rapidly reversible upon withholding the medication.
TRIAL DESIGNThe multicenter trial, which is not yet open for enrollment, will compare the efficacy of AM0010 in combination with FOLFOX versus FOLFOX alone in an estimated 566 patients. Patients randomized to the experimental arm will receive AM0010 (5mcg/kg) administered on days 1-5 and 8-12 via subcutaneous injection, plus standard FOLFOX-based therapy for pancreas and colon cancer (dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5-FU 400 mg/m2 and a 46-hour infusion of 5-FU 2400 mg/m2) given intravenously once every 2 weeks. The primary endpoint of the study is overall survival (OS), and the secondary endpoints are progression-free survival and overall response rate.
WHO IS ELIGIBLE?The trial is designed for patients 18 years and older with adenocarcinoma of the pancreas whose disease has progressed after first-line gemcitabine therapy. Patients must complete prior chemotherapy at least 2 weeks before randomization, with recovery from toxicity to grade 1 or baseline and no prior radiation therapy or investigational therapy for metastatic disease.
If successful when paired with FOLFOX, the combination has potential to fulfill an unmet need for these patients, particularly those with metastatic disease who progress from initial chemotherapy and have an OS of ≤6 months.