New Study Seeks to Assess Tolerability of Emerging Nivolumab Combination

New Study Seeks to Assess Tolerability of Emerging Nivolumab Combination

Elizabeth R. Plimack, MD, MS

An upcoming phase I trial seeks to evaluate a combination of interferon gamma-1b (ACTIMMUNE) and nivolumab (Opdivo) in patients with advanced solid tumors who have progressed on at least one prior systemic therapy.

According to a press release from Horizon Pharma¹, the company is collaborating with Fox Chase Cancer Center - Temple Health to assess the feasibility of the interferon gamma-1b and nivolumab combination. Patients enrolled in the study will be given one week induction phase of interferon gamma-1b for three cycles (starting dose 50 mcg/m2 subcutaneously), a combination phase of interferon gamma-1b and nivolumab for three cycles (3 mg/kg intravenously), and then treatment with single-agent nivolumab for up to one year.

“We are hoping to increase the proportion of patients for whom PD-1 inhibitors, in this case nivolumab, are effective,” said Geoff Curtis, Group Vice President of Corporate Communications at Horizon Pharma, in an interview withTargeted Oncology. “Based on pre-clinical cell-line research, there is evidence that interferon gamma-1b enhances cellular expression on endothelial cells and on some tumor cells, which may enhance the effect of PD-1 inhibitors.”

The study aims to asses the safety and tolerability of the combination in patients with a wide variety of cancers, including squamous cell cancer of the head and neck (SCCHN). Tumor assessments for patients enrolled will occur after three cycles of the combination therapy, as well as every three cycles subsequent to the initial assessment.

Secondary objectives for the study include overall response rate (ORR), progression free survival (PFS), and overall survival (OS). Correlatively analyses will also be included in the data. Initial accrual for the study will take place utilizing a modified 6+6 design, and pending the endpoints are met, expansion cohorts in both renal cell carcinoma (RCC) and ulcerative colitis (UC) will form.

Curtis said the estimated enrollment for the trial is 15 people, and if the trial proves successful, the next step would be to move on to a phase II trial with cohorts of patients with different advanced solid tumors.

"Nivolumab and other PD-1 inhibitors have demonstrated clinical benefit in multiple trials across many advanced solid tumor types," said Elizabeth R. Plimack, MD, MS, associate professor of medical oncology, director of Genitourinary Clinical Research, Fox Chase Cancer Center - Temple Health, in the press release. "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."

According to the trial’s website², inclusion criteria for the phase I trial are that patients must exhibit a histologically or cytologically confirmed metastatic solid tumor that responds to anti-PD-1 therapy or has the capacity to up-regulate PD-L1.

Patients must also have received at least 1 line of systemic therapy in the metastatic setting (or prior immunotherapy barring cessation due to drug-related toxicity), a measurable disease as defined by RECIST criteria, a disease site amenable to pretreatment and on-treatment core biopsies, must be over the age of 18, and have a performance status of either 0 or 1 according to Eastern Cooperative Oncology Group (ECOG).

Tumors types that will be accepted into the study include RCC, UC, melanoma, non small cell lung cancer (NSCLC), small cell lung cancer, squamous cell cancer of the head and neck (SCCHN), ovarian carcinoma, triple negative breast cancer, gastric cancer, microsatellite instability expressing (MSI-high) colon cancer, hepatocellular carcinoma, mesothelioma, gastrointestinal stromal tumors, endometrial carcinoma, liposarcomas, chondrosarcomas, and uterine sarcomas.

"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," said Jeffrey W. Sherman, M.D., FACP, executive vice president, research and development and chief medical officer, Horizon Pharma plc. "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."

The study is set to start during December 2015 with an estimated completion date of December 2018 and primary completion date in December 2017.

References

1. Ir.horizon-pharma.com. Horizon Pharma plc and Fox Chase Cancer Center Temple Health Initiate Phase 1 Study to Evaluate ACTIMMUNE(R) (interferon gamma-1b) in Combination With Nivolumab in Patients With Advanced Solid Tumors (NASDAQ:HZNP). 2015. Available at: http://ir.horizon-pharma.com/releasedetail.cfm?ReleaseID=946810. Accessed December 18, 2015.
2. Clinicaltrials.gov. Combination of Interferon-gamma and Nivolumab for Advanced Solid Tumors - Full Text View - ClinicalTrials.gov. 2015. Available at: https://clinicaltrials.gov/ct2/show/NCT02614456?term=nivolumab+interferon&rank=1. Accessed December 18, 2015.