Medical Oncology Unit, Austin Health, Heidelberg, Australia; Peter MacCallum Cancer Centre, East Melbourne, Australia; Monash Health and Monash University, Melbourne, Australia; Austin Health, Melbourne, Australia; Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia; Peter MacCallum Cancer Centre, Melbourne, Australia; Royal Melbourne Hospital, Parkville, Australia; Monash Health, Melbourne, Australia; Austin Health, Heidelberg, VIC, Australia; Olivia Newton-John Cancer Research Institute, Melbourne, Australia
Background: Patients (pts) with rare cancers represent an unmet medical need and have an inferior overall survival compared to patients with more common malignancies. Due to their low frequency, no therapies, including immunotherapies, have systematically been investigated in this population. Ipilimumab (ipi)/Nivolumab (nivo) combination treatment has demonstrated significant clinical activity in pts with advanced melanoma and renal cell carcinoma and response rates with this regimen are higher compared to single agent anti-PD-1 therapy. This phase II study assessed the efficacy and safety of ipi/nivo in rare cancer pts. Methods: 60 pts with advanced rare upper gastrointestinal (GI), neuroendocrine (NE) and gynaecological (GY) malignancies were enrolled in 3 cohorts. Patients received nivo 3mg/kg and ipi 1mg/kg every 3 weeks for four doses, followed by nivo 3mg/kg every 2 weeks. Treatment continued for up to 96 weeks, or until disease progression or the development of unacceptable toxicity. Response (RECIST 1.1) was assessed every 12 weeks. The primary endpoint was clinical benefit rate (CBR), CR, PR and SD. Exploratory endpoints include correlation of efficacy with relevant biomarkers including PDL1 status and tumour mutation burden. Results: For all patients the disease control rate (DCR) (CR + PR + SD) was 60% For each of the 3 baskets Objective Responses/DCR were 35%/40% (GI), 30%/80% (NE) and 30%55% (GY). Grade 3/4 immune related adverse events were detected in 31% of pts. The results of correlative biomarker studies will be presented at the meeting. Conclusions: Ipi/Nivo combination treatment has efficacy in a wide range of advanced rare malignancies. Immune related toxicity is in keeping with previously reported clinical trials using the same dosing regimen