Oncofid-P-B for the Treatment of BCG Unresponsive Carcinoma in Situ (CIS) of Bladder: Results of European Multicenter Phase I Study at the End of 12- Consecutive Weeks Intensive Course.

486 Background: There is an unmet clinical need for new drugs able to delay or avoid cystectomy in patients with CIS unresponsive to BCG. Here, we report the safety and efficacy of Oncofid−P-B, is a new drug that originates from the chemical conjugation of paclitaxel with hyaluronic acid, in patients with CIS unresponsive or intolerant to BCG. Methods: This is an open-label, single arm, multicenter international study (Registered as EudraCT Number: 2016-004144-11) to assess safety, tolerability and efficacy of Oncofid-P-B administered in 20 patients with CIS, unresponsive or intolerant to BCG and unwilling or unfit for cystectomy. Oncofid-P-B was administered by intravesical instillation for 12 consecutive weeks (intensive phase). A 12 monthly (maintenance phase) in patients who were in complete response (CR) after the intensive phase is ongoing. The primary end-point was the overall safety profile. Secondary endpoints included i) efficacy after the intensive phase ii) compliance, iii) systemic absorption. The CR is defined as a negative cystoscopy including biopsy of the urothelium and negative cytology. Statistics will be calculated, as appropriate, for the quantitative variables. Results: Of the 20 enrolled patients who completed the intensive phase, CR was achieved in 15 patients (75%). Seven G1-G2 drug-related adverse events (AEs) were reported in only three patients over 240 instillations. No drug related serious AEs and no study withdrawal have been reported. In all plasma samples, the drug concentration was always below the Limit of Quantification (0.1ng/ml). Over 15 patients who ended the intensive course without CIS recurrence, five already completed the 12-month maintenance phase (four patients with no recurrence of CIS), thirteen were disease free after three months and six are completing the maintenance. Conclusions: The excellent safety profile of Oncofid-P-B is well positioned as compared with the most recent competitors, thus confirming its potential as therapeutic option in BCG unresponsive CIS patients, also with a prolonged treatment schedule, and deserves further clinical evaluation. Clinical trial information: 2016-004144-11.