Sacituzumab govitecan in patients with advanced or metastatic radioactive-iodine refractory thyroid carcinoma: The phase 2 SETHY, GETNE-T2318 trial.

Abstract

TPS6130 Background: Current treatment options for advanced or metastatic differentiated thyroid carcinoma (DTC) with vascular endothelial growth factor inhibitors provide clinical benefit, despite the fact that most patients will acquire treatment resistance, whereas, advanced or metastatic anaplastic thyroid carcinoma (ATC) still lacks effective treatment options. Trophoblast cell surface antigen 2 (TROP-2) is highly expressed at the membrane of DTC and ATC, while it is rarely expressed in normal tissues. Moreover, TROP-2 is associated with tumor aggressiveness and poor prognosis. Targeting TROP-2 with sacituzumab govitecan, an antibody-drug conjugate with a SN-38 payload, showed efficacy in other cancer types such as triple negative or HER positive breast cancer or urothelial cancer and may be an effective treatment for thyroid carcinoma. SETHY is the first clinical trial with antibody-drug conjugates in thyroid cancer. Methods: The SETHY trial is a single-arm, multicohort, prospective, phase 2 trial of sacituzumab govitecan in patients with advanced or metastatic radioactive-iodine refractory thyroid cancer being recruited in 10 hospitals in Spain. Patients are ≥ 18 years, ECOG 0-1, should have recovered from any prior toxicity and have an adequate organ function. Patients will be included in two cohorts: DTC after progression (PD) to 1-3 prior systemic therapies (cohort 1) or ATC in 1st-line treatment or after failure of any systemic therapy (Cohort 2). Prior topoisomerase 1 inhibitors are not permitted. All patients will receive sacituzumab govitecan (10 mg/kg intravenously) on Days 1 and 8 of every 21-days cycle, until PD, death, study withdrawal, or unacceptable toxicity. Computed tomography (CT) or magnetic resonance imaging (MRI) scans and blood monitoring of tumor markers are performed every 12 weeks (Q12W) until PD. The primary endpoint is objective response rate (ORR) according to RECIST v1.1. Secondary endpoints include disease control rate, duration of response, progression-free survival, overall survival, safety, and quality of life (assessed through EORTC QLQ-C30 at baseline and Q12W until PD). Archival tumor samples will be collected at screening for retrospective central evaluation of TROP-2 expression levels and ancillary studies. The study uses a Simmon-II design considering a ORR of 5% as null hypothesis and an alternative ORR of 20% (α=0.1 one sided, β=0.2). In total, the study requires a total of 21 patients per cohort; 12 in the 1st stage and, if at least one response is reported, 9 additional in the 2nd stage. The study is approved and open to patient selection in Spain. Clinical trial identification: EU CT: 2023-504898-20-00 / NCT06235216 Clinical trial information: NCT06235216 .