Pertuzumab plus trastuzumab (P+T) in patients (pts) with bladder (BC) and ovarian cancer (OC) with ERBB2/3 alterations (alt): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with genomic alt. Results of two cohorts of pts with BC or OC with alt treated with P+T are reported. Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Recommended dosing was P at an initial dose of 840 mg intravenously (IV), then 420 mg IV every 3 weeks (wks) and T at an initial dose of 8 mg/kg IV, then 6 mg/kg IV every 3 wks until disease progression. Primary endpoint was disease control (DC) per investigator defined as complete (CR) or partial (PR) response per RECIST v.1.1, or stable disease (SD) of at least 16 wks duration (SD16+). CR was based on radiographic assessment. For both cohorts, Simon 2-stage design was based on a null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage I had DC, 18 more pts were enrolled; otherwise, the cohort was closed. If ≥7 of 28 pts had DC, the null DC rate was rejected. Secondary endpoints were objective response (OR), progression-free survival (PFS), overall survival (OS), duration of response and SD, and safety. 28 pts with alt were enrolled in each cohort. The table shows demographics and outcomes. For the BC cohort, 2 CRs ( amplification [amp, n=1] and amp and mutation [mut, n=1]), 5 PRs ( amp [n=3], amp and mut [n=1], and mut [n=1]) and 3 SD16+ ( mut [n=3]) were observed for DC rate of 37% (90% CI, 24 to 100) and OR rate of 25% (95% CI, 11 to 45). The null DC rate was rejected (p=0.005). For the OC cohort, 2 PRs ( amp [n=1] and mut [n=1]) and 3 SD16+ ( amp [n=2] and amp and mut [n=1]) were observed for DC rate of 25% (90% CI, 10 to 100) and OR rate of 7% (95% CI, 1 to 24). The null DC rate was not rejected (p=0.29). Across both cohorts, 4 pts had 6 tx-related serious adverse events (SAE) including: infusion-related reaction, confusion, diarrhea, and fever, and 2 pts had 1 grade 3 tx-related adverse event (AE) each including: GGT increase and lymphopenia. No pts had grade 5 SAEs. P+T met prespecified criteria to declare clinical activity in pts with BC with alt, but not in pts with OC. Additional study is warranted to confirm the efficacy of P+T in pts with BC with alt. .

Duke Scholars

Author Susan Halabi Biostatistics & Bioinformatics, Division of Biostatistics