Pertuzumab and Trastuzumab in Patients With ERBB2/3-Altered Urothelial or Ovary/Fallopian Tube Cancer: Results From the Targeted Agent and Profiling Utilization Registry Study.

PURPOSE: TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations. Results of two cohorts of patients with urothelial (UC) or ovarian/fallopian tube cancer (OC/FTC) with ERBB2/3 alterations treated with pertuzumab plus trastuzumab (P + T) are reported. METHODS: Eligible patients had advanced cancer, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with ERBB2/3 alterations, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration. Simon's two-stage design is based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety. RESULTS: Patients with UC (n = 28) or OC/FTC (n = 25) with ERBB2/3 alterations were enrolled from March 2017 to June 2023. In the UC cohort, the DC and OR rates were 37% (90% CI, 24 to 100) and 25% (95% CI, 11 to 45), respectively. The null hypothesis of 15% DC rate was rejected (P = .005). In the OC/FTC cancer cohort, the DC and OR rates were 23% (90% CI, 9 to 100) and 8% (95% CI, 1 to 26), respectively. The null hypothesis of 15% DC rate was not rejected (P = .35). Six patients had at least one grade 3-5 adverse event (AE) or serious AE at least possibly related to treatment. CONCLUSION: The combination of P + T met prespecified criteria to declare a signal of activity in patients with UC with ERBB2/3 alterations, but not in patients with OC/FTC.

Duke Scholars

Author Susan Halabi Biostatistics & Bioinformatics, Division of Biostatistics