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A phase II study of cabozantinib as first-line treatment in metastatic collecting ducts carcinoma: The BONSAI trial.

578 Background: Metastatic collecting ducts carcinoma (mCDC) is a rare and aggressive disease, characterized by a poor prognosis; its treatment represents an unmet medical need. We aimed to evaluate the activity and safety of cabozantinib (cabo) in mCDC. Methods: This is a prospective, monocentric, single-arm phase II trial evaluating cabo in patients (pts) with untreated mCDC. Cabo was administered at the dose of 60 mg orally once daily until disease progression (evaluated by RECIST 1.1 criteria) or unacceptable toxicity. Primary endpoint was objective response rate. Secondary endpoints were progression-free survival, overall survival and safety profile. Exploratory objectives include the identification of somatic mutations and the mutational load on tissue samples; plasma and viable peripheral blood mononuclear cells were studied for immune related biomarker profiling. Results will be crossed with clinical data in terms of response rate, to detect any predictive value of blood immune cell profiling. A central pathological review before study entry is mandatory. The study design is based on a Simon’s two stage optimal design: in the first step at least 2 responses in 9 pts enrolled are needed to go to the second stage of the study (14 additional pts). Results: From January 2018 to September 2018, 11 pts with mCDC have been so far enrolled, nine of which started study treatment. Median age was 58 years, 8 pts were male and 1 female, 7 pts received a previous nephrectomy. The most common metastatic sites were bone and abdominal lymphnodes (5 pts each), followed by liver and lung (2 pts each). Two pts had a partial response as best response, 2 had a stable disease, 3 had a progressive disease and 3 pts died for early progression. Treatment was feasible and well tolerated. All pts reported at least one grade (G) 1-2 adverse events (AEs): the most common were asthenia, diarrhea, anorexia and nausea, hand-foot syndrome, hypertension and dysgeusia. No G3-4 AEs were reported. Genetic and immunological essays are ongoing to assess the immunomodulatory properties of cabozantinib and potential predictive factors. Conclusions: Cabo was safe and active in CDC. The second stage and biomarkers analyses are ongoing. Clinical trial information: NCT03354884.