Combination Immunotherapy in Rare Cancers Under InvesTigation

This is a phase 2 clinical trial of nivolumab combined with ipilimumab in immunotherapy sensitive rare cancers. This study will allow an evaluation of the clinical benefit, as measured by progression free survival (PFS) \>6 months and overall survival (OS), provided by nivolumab combined with ipilimumab. 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, patients are often excluded from clinical trials with newer agents. CA209-538 examined this treatment combination in three 'baskets' of rare cancers: rare upper gastrointestinal, gynaecological and neuroendocrine cancers. The cancers on study all individually had an incidence of \<2/100000/year. 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 rare cancer patients. Given the success of cancer immunotherapy with checkpoint regulators such as ipilimumab and nivolumab in a range of different cancer types, it was postulated that these agents could be beneficial in rare cancers and improve the overall outlook of patients with these conditions. CA209-538 enrolled 120 rare cancer patients on study, clinical benefit rate was \>30% across all baskets, long term survival follow-up is underway. This study will enrol 240 participants, across 4 cohorts with histotypes which demonstrated clinical benefit on CA209-538. All participants will receive ipilimumab and nivolumab as combination immunotherapy.