Pertuzumab Plus Trastuzumab in Patients With Biliary Tract Cancer With Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study.

Purpose: Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with biliary tract cancer (BTC) with amplification, overexpression, or mutation treated with pertuzumab plus trastuzumab are reported.

Methods: Eligible patients had advanced BTC, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with alterations, and a lack of standard treatment options. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease of at least 16+ weeks duration (SD16+) according to RECIST v1.1. Secondary end points included OR, progression-free survival, overall survival, duration of response, duration of stable disease, and safety.

Results: Twenty-nine patients were enrolled from February 2017 to January 2022, and all had advanced BTC with an alteration. One patient was not evaluable for efficacy. One complete response, eight partial responses, and two SD16+ were observed for DC and OR rates of 40% (90% CI, 27 to 100) and 32% (95% CI, 16 to 52), respectively. The null hypothesis of 15% DC rate was rejected ( = .0015). Four patients had at least one grade 3 adverse event (AE) or serious AE at least possibly related to treatment: anemia, diarrhea, infusion-related reaction, and fatigue.

Conclusion: Pertuzumab plus trastuzumab met prespecified criteria to declare a signal of activity in patients with BTC and amplification, overexpression, or mutation.