A phase II open-label study of sacituzumab govitecan in patients with previously treated locally advanced, recurrent, or metastatic cholangiocarcinoma (SIGNA).

Abstract

TPS651 Background: Cholangiocarcinoma (CCA) is a highly aggressive cancer with limited treatment options. Trop-2, a transmembrane calcium signal transducer, plays a key role in cellular self-renewal, proliferation, and transformation, thereby promoting tumorigenesis. Its overexpression has been associated with disease progression and shorter survival in several epithelial tumors, including CCA. Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of a humanized anti-trophoblast cell-surface antigen 2 (Trop-2) monoclonal antibody coupled to SN-38, the active metabolite of the topoisomerase inhibitor, irinotecan. Based on the results from the Phase III ASCENT trial, SG was approved by the FDA for treating relapsed or refractory triple-negative breast cancer and hormone receptor-positive breast cancer, regardless of Trop-2 expression. Given Trop-2's expression in CCA, SG is being investigated as a potential treatment option in this setting. Methods: This Phase II, non-randomized, open-label, single-arm study is being conducted at the University of Kansas Cancer Center and its affiliated sites. Eligibility : Key inclusion criteria include patients with locally advanced, recurrent, or metastatic CCA who have undergone at least one line of prior therapy, have adequate archival tissue for biomarker evaluation or are willing to undergo a biopsy, and have an ECOG performance status of 0-1. Key exclusion criteria include known homozygosity for the UGT1A1*28 allele, which is associated with irinotecan toxicity, and prior treatment with topoisomerase I inhibitors. Treatment Plan : SG is administered at 10 mg/kg intravenously on Days 1 and 8 of every 21-day cycle. Imaging will be performed every 6 weeks. Biopsies will be required both prior to treatment and on-treatment (between Days 15-21 of Cycle 1). Objectives : Primary objective: To determine the anti-tumor activity of SG as measured by the overall response rate (ORR) according to RECIST 1.1. Secondary objectives: To assess treatment safety in participants who have received at least one dose of SG, and to evaluate anti-tumor activity based on progression-free survival (PFS), disease control rate (DCR), and overall survival (OS). Statistical Plan : The sample size (n=22) was calculated using a modified Simon two-stage design, hypothesizing an improvement in ORR to 25%, compared to a baseline value of 8%. In the first stage, 14 patients will be enrolled. If ≤1 participant demonstrates an ORR, the study will be stopped for futility. If ≥2 participants show ORR, an additional 8 patients will be enrolled (total n=22). The study will be deemed successful if ≥4 participants achieve an ORR. This design provides 80.9% power with an 8.5% type I error rate. Stopping rules include halting the trial if the grade 4-5 treatment-related toxicity rate reaches 10%. Enrollment is ongoing. Clinical trial information: NCT06178588 .