Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of UC pts with ERBB2 or ERBB3 amplification, overexpression or mutation treated with P+T are reported. Methods: Eligible pts had advanced UC, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts matched to P+T had UC with ERBB2 or ERBB3 amplification or overexpression or a pre-specified ERBB2 mutation. Recommended dosing was P at an initial dose of 840 mg intravenously (IV) over 60 minutes (m), then 420 mg IV over 30-60 m every 3 weeks (wks), and T at an initial dose of 8 mg/kg IV over 90 m, then 6 mg/kg IV over 30-60 m every 3 wks until disease progression. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-eight female pts were enrolled from August 2017 to November 2019; all pts were evaluable for efficacy and toxicity. Demographics and outcomes are summarized in Table. Twenty-two pts had tumors with ERBB2 amplification (21) or overexpression (1); 4 tumors had ERBB2 mutations; 1 tumor had ERBB3 amplification; 1 tumor had both an ERBB2 amplification and mutation. Two PR and 7 SD16+ were observed in pts with ERBB2 amplification, and 1 SD16+ was observed in a pt with ERBB2 V8421 mutation only (no amplification) for DC and objective response (OR) rates of 37% (95% CI, 21% to 50%) and 7.1% (95% CI, 0.8% to 24%), respectively. One pt experienced grade 3 muscle weakness at least possibly related to P+T. Conclusions: P+T demonstrated evidence of anti-tumor activity in heavily pre-treated UC pts with ERBB2 amplification or certain mutations. Additional study is warranted to confirm the efficacy of P+T in this pt population. Clinical trial information: NCT02693535