Phase II Parallel Arm Study of Sacituzumab Govitecan-Hziy in Patients With Advanced Thymoma or Thymic Carcinoma.

BACKGROUND

Thymic epithelial tumors (TETs), including thymoma and thymic carcinoma, are rare thoracic tumors of the anterior mediastinum. For those with advanced disease, platinum-based chemotherapy is used as first-line treatment. However, there is no standard regimen established for TET at progression after initial therapy, and treatment options for advanced/recurrent TETs are limited. Trop-2, a transmembrane glycoprotein, is overexpressed in solid tumors including thymomas and thymic carcinomas. Sacituzumab govitecan-hziy, a Trop-2-directed antibody-drug conjugate, has shown efficacy and safety in several tumors including breast cancer. The overexpression of Trop-2 in TETs and the clinical efficacy in other malignancies provide rationale for exploring its use in thymoma and thymic carcinoma.

METHODS

This open-label, single-arm, parallel cohort, multi-center study assesses the safety and efficacy of sacituzumab govitecan-hziy in patients with advanced thymoma (cohort A) and thymic carcinoma (cohort B) who have received at least 1 prior line of systemic therapy (NCT06248515). The study employs a Simon optimal 2-stage design, enrolling patients with adequate performance status, measurable disease, and adequate organ function. Sacituzumab govitecan-hziy is administered at a fixed dose of 10 mg/kg weekly on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Follow-up continues every 6 months for 2 years postdiscontinuation. Archival tissue is obtained prior to initiation of study treatment with an optional biopsy at the time of progression. In cases where archival tissue is not available, a fresh biopsy is obtained at baseline. The primary endpoint is investigator-assessed response rate using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST) criteria, with tumor imaging assessments every 2 cycles during the first 3 months and every 3 cycles thereafter. Secondary endpoints comprise adverse events by Common Terminology Criteria for Adverse Events v5.0, median and 6-month progression-free survival, duration of response, and overall survival. For each cohort, 9 patients will be enrolled. If 0 of the 9 achieve a response, no further patients will be enrolled in that cohort. If 1 or more of the first 9 patients has a response, accrual will continue until a total of 17 patients have been enrolled in that cohort.