Study Rationale Clinically advanced rare cancers pose a significant clinical challenge because evidence based treatments are seldom available for patients suffering from these malignancies. Despite little evidence that shows clinical benefit, these patients are often treated with chemotherapeutic agents that are used in patients with more common malignancies that arise from the same anatomical site. Furthermore, because of small numbers, they are often excluded from clinical trials with newer agents. The rare care project has defined a rare malignancy as a cancer with an incidence of less than 6/100000/year. It is estimated that 42,000 people are diagnosed with a form of rare or less common cancer in Australia every year (www.canceraustralia.gov.au). The cancer specific survival of patients diagnosed with a rare malignancy is significantly lower than with common cancers highlighting the need to improve management and treatment of these patients. Given the recent success of cancer immunotherapy with checkpoint regulators such as ipilimumab and nivolumab in a whole range of different cancer types, it can be postulated that these agents could be beneficial in rare cancers and improve the overall outlook of patients with these conditions. It is proposed here that patient cohorts which fall within three distinct tumour streams will be examined, with all patients receiving ipilimumab and nivolumab as combination immunotherapy. The three tumour streams are defined as: upper GI malignancies (comprising intra-hepatic/ extra-hepatic cholangiocarcinomas,gall bladder cancers and duodenal cancers).); neuroendocrine tumours (inc. Pancreatic, bronchial and intestinal carcinoid tumours) and rare gynaecological tumours (including but will not be limited to: vaginal or vulval carcinomas, clear cell carcinoma of the ovary, low grade serous ovarian cancer, mixed mullarian tumours (carcinosarcoma), sarcomas of the female genital tract and granulosa cell tumours). Although overall response rates for individual tumour types will not be established due to sample size (target 20 patients per tumour stream, n=60 total), descriptive information of individual patient responses will guide immune-directed therapies to responsive rare tumour types and may be broadened to tumour streams.