Guo, Shuangli

348 Background: Patients (pts) with mUC have few treatment options beyond the second-line setting. HER2 gene amplification has been reported in a minority of pts with UC, but there have been anecdotal reports of the activity of HER2-targeted agents. MyPathway is a multi-basket study evaluating the efficacy and safety of targeted therapies in non-indicated tumor types harboring relevant molecular alterations. We present preliminary data for pts with HER2-positive mUC receiving HER2-targeted treatment with pertuzumab + trastuzumab. Methods: MyPathway (NCT02091141) is an open-label, multicenter, phase IIA study. Pts in this subset analysis had refractory mUC with HER2 amplification or putative activating mutations by gene sequencing, FISH, or IHC. Pts received standard doses of pertuzumab + trastuzumab without chemotherapy until disease progression or unacceptable toxicity. The primary endpoint is investigator-assessed overall response rate (RECIST v1.1). Results: As of July 31, 2016, 12 pts with platinum-resistant HER2-positive mUC (HER2-amplified, n=9; HER2-mutated, n=3) have been enrolled. At a median follow-up of 5.4 (range 0.9–14.5) mos, 1 pt had complete response (CR, ongoing at 12.5 mos), 2 had partial responses (PR; duration of response, 3.7 and 5.5 mos), and 2 had stable disease (SD) for >4 mos (Table). Safety was consistent with the product labels. Conclusions: Preliminary results indicate that the combination of pertuzumab + trastuzumab has activity in previously treated HER2-amplified mUC, including a durable CR in a pt with peritoneal metastases. Accrual to MyPathway is ongoing. Clinical trial information: NCT02091141. [Table: see text]