1940TiP - Sacituzumab govitecan in patients with advanced or metastatic radioactive-iodine refractory thyroid carcinoma and anaplastic thyroid carcinoma: The phase II SETHY, GETNE-T2318 trial design

Background

Trophoblast cell surface antigen 2 (TROP-2) is highly expressed at the membrane of differentiated thyroid carcinoma (DTC) and anaplastic thyroid carcinoma (ATC), while it is rarely expressed in normal tissues. TROP-2 is associated with tumor aggressiveness and poor prognosis. Sacituzumab govitecan, an antibody-drug conjugate with a SN-38 payload, has shown efficacy in other cancer types and could be an effective treatment for DTC and ATC. SETHY is the first clinical trial with antibody-drug conjugates in thyroid cancer.

Trial design

The SETHY trial is a single-arm, multicohort, prospective, phase 2 trial to determine the efficacy and safety of sacituzumab govitecan in patients (pts) with advanced or metastatic radioactive-iodine refractory (RAI-R) DTC and advanced ATC. Pts are ≥ 18 years, ECOG 0-1, should have recovered from any prior toxicity and have an adequate organ function. Pts will be included in two cohorts: RAI-R 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 pts 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. 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 pts 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 pts selection in 10 sites in Spain.

Clinical trial identification

EU CT: 2023-504898-20-00 NCT06235216.

Editorial acknowledgement

We acknowledge MFAR Clinical Research staff for their assistance in the development of this abstract.

Legal entity responsible for the study

GETNE.

Funding

GETNE through industry collaborator Gilead.

Disclosure

A. Garcia Alvarez: Financial Interests, Personal, Advisory Board: ADACAP (Novartis); Other, Expenses (Travel, Congress inscription): Advanz, Eisai, Ipsen, ADACAP (Novartis). J. Martínez-Trufero: Financial Interests, Personal, Advisory Board, Advisory Board meeting: Pharmamar, Eisai, GSK, Deciphera, Boehringer, Eisai; Financial Interests, Personal, Invited Speaker: Roche, Eisai, Merck, Medicamenta, MSD, Ipsem; Financial Interests, Personal, Advisory Board, Meetting travel expenses: Roche, Pharmamar; Financial Interests, Institutional, Advisory Board, Clinical trail: RAIN Therapeutics, Blueprint, Lilly, Kariopharm Therapeutics, Syneous Heath, Boehringer, Alaya Pharmaceuticals, SynOx Therapeutics, BioNTech, Daiichi Sankyo; Financial Interests, Advisory Board, Spanish group of Sarcoma Research: GEIS Group, TTCC Group. T. Alonso-Gordoa: Financial Interests, Personal, Advisory Board: Ipsen, Pfizer, Roche, Sanofi, Bayer, Janssen-Cilag, Eisai, Novartis Advenced Accelerator Aplications, Lilly, Bristol Myers Squibb, Astellas; Non-Financial Interests, Project Lead: Ipsen, Pfizer, Johnson & Johnson. M. Plana Serrahima: Financial Interests, Personal, Invited Speaker, X: MSD; Financial Interests, Personal, Invited Speaker: Eisai. E. Grande: Financial Interests, Personal, Invited Speaker: Adacap, Astra Zeneca, Bristol Myers Squibb, Eisai, Eusa Pharma, Ipsen, Janssen, Lilly, Merck KGa, Pfizer, Roche, Dr. Reddy's, Adium; Financial Interests, Personal, Advisory Board: Astellas, Bayer, MSD, Novartis, Sanofi-Genzyme, Abbie; Financial Interests, Institutional, Advisory Board: Caris Life Sciences, ONCODNA (Biosequence); Financial Interests, Institutional, Research Grant, Independent research grant: Astellas, AstraZeneca, Lexicon, MTEM/Threshold, Nanostring Technologies, Pfizer, Roche, Merck; Financial Interests, Institutional, Coordinating PI, Independent research grant: IPSEN; Non-Financial Interests, Other, AD BOARD member: ENETS; Non-Financial Interests, Member of Board of Directors: GETNE, GUARD Consortium, Grupo centro de Tumores Genitourinarios. J. Hernando: Financial Interests, Personal, Advisory Board: Eisai, Ipsen, Novartis, AAA, Angalin, Pfizer, Roche. J. Capdevila Castillon: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Ipsen, Exelixus, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Merck Serono; Financial Interests, Personal, Advisory Board: Pfizer, Ipsen, Exelixus, Bayer, Eisai, Advanced Accelerator Applications, Sanofi, Lilly, Merck Serono, Esteve, ITM, Novartis; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Research Grant: AstraZeneca, Advanced Accelerator, Bayer, Eisai, Novartis, Pfizer; Financial Interests, Institutional, Research Grant: Roche, Gilead; Financial Interests, Institutional, Coordinating PI: ITM, Boehringer Ingelheim. All other authors have declared no conflicts of interest.