Horizon Pharma plc, based in Dublin, Ireland, has announced that it has initiated a Phase 1 clinical study to evaluate Actimmune (interferon gamma-1b) in combination with nivolumab, an immunoglobulin (Ig) G4 monoclonal antibody (AKA anti-PD-1 human monoclonal antibody MDX-1106; Opdivo) in advanced solid tumors. The company is co-sponsoring the trial with Fox Chase Cancer Center Temple Health of Philadelphia, Pennsylvania.
Actimmune, a biologically manufactured protein similar to a protein produced by the immune system to help prevent infection, is currently approved by the U.S. Food and Drug Administration (FDA) for use in two rare diseases: Chronic Granulomatous Disease (CGD), a genetic disorder that affects the functioning of some cells of the immune system, and severe, malignant osteopetrosis (SMO), a genetic disorder that affects normal bone formation.
The trial, titled “Combination of Interferon-gamma and Nivolumab for Advanced Solid Tumors” (ClinicalTrials.gov Identifier: NCT02614456), is currently recruiting participants. For conditions of eligibility, contacts, and site locations visit the ClinicalTrials.gov website here.
This Phase I, open-label combination study tests Actimmune (interferon gamma-1b) with nivolumab, a PD-1 inhibitor, in patients with advanced solid tumors that have progressed despite at least one prior systemic therapy, which may include an immunotherapy. Patients will be treated in a one-week induction phase with Actimmune (starting dose 50 mcg/m2 subcutaneously), followed by a combination phase with Actimmune and nivolumab (3 mg/kg intravenously) for three cycles, and then in a single-agent phase of nivolumab for up to one year. The study will primarily assess the safety and tolerability of the drug combination. Secondary objectives, including overall response rate, progression free survival and overall survival, will also be assessed, as will various correlative analyses. Initial accrual will occur using a modified 6+6 design, and if endpoints for safety (using dose-limiting toxicity criteria) are met, expansion cohorts in renal cell carcinoma (kidney cancer) and urothelial carcinoma (bladder cancer) are planned for up to 15 patients per cohort. The trial is expected to conclude in December 2018.
“We are eager to explore the safety and efficacy of Actimmune in combination with nivolumab in multiple, difficult-to-treat cancers that are often inoperable or have become unresponsive to standard therapies,” says Jeffrey W. Sherman, M.D., FACP, executive vice president, research and development and chief medical officer, Horizon Pharma, in a release. “Through this study, we hope to find that the addition of Actimmune to PD-1 inhibitors, like nivolumab, could potentially lead to better patient outcomes and inform our strategy for future Actimmune indications to pursue in Phase 2 trials.”
“Nivolumab and other PD-1 inhibitors have demonstrated clinical benefit in multiple trials across many advanced solid tumor types,” says Elizabeth R. Plimack, MD, MS, an associate professor of medical oncology and director of Genitourinary Clinical Research at Fox Chase. “However, some patients benefit from these therapies while others do not. Based on work from Fox Chase and other laboratories, we have strong evidence to suggest that Actimmune may increase the proportion of patients for whom nivolumab is effective. We are excited to test this hypothesis as part of this Phase 1 clinical trial.”
Horizon Pharma is a biopharmaceutical company focused on improving patients’ lives by identifying, developing, acquiring, and commercializing differentiated and accessible medicines that address unmet medical needs. The company markets seven medicines through its orphan, primary care, and specialty business units.
Fox Chase Cancer Center, part of the Temple University Health System, is a leading cancer research and treatment center. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the many awards, including two Nobel prizes. Fox Chase physicians are also routinely recognized in national rankings, and the center’s nursing program has received the Magnet recognition for excellence four consecutive times. Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. For information, call 1-888-FOX CHASE or (1-888-369-2427), or visit: www.foxchase.org/?gclid=CKLTiZO63skCFYU9aQodQOUBUQ
Additional information on Actimmune is available at: www.ACTIMMUNE.com.
Horizon Pharma plc
Fox Chase Cancer Center
National Institutes Of Health National Cancer Institute