A phase 3 study of ateganosine (THIO; 6-thio-2'-deoxyguanosine) sequenced with immune checkpoint inhibitor (ICI) versus standard-of-care chemotherapy in ICI-resistant advanced NSCLC: THIO-104 trial in progress.

Abstract

TPS8672 Background: Despite progress in the treatment of advanced non-small cell lung cancer (NSCLC), therapeutic options remain scarce for patients who have developed resistance to immune checkpoint inhibitors (ICIs). Ateganosine (THIO; 6-thio-2'-deoxyguanosine), a telomere-targeting agent, is selectively recognized by telomerase and integrated into the telomeres of cancer cells. Once incorporated, Ateganosine compromises the telomere structure and function, leading to ‘uncapping’ of the chromosome ends and thus resulting in rapid tumor cell apoptosis. Methods: THIO-104 is a multicenter, open-label, randomized Phase 3 study enrolling approximately 300 subjects with histologically confirmed advanced/metastatic NSCLC. Eligible participants must have received two prior lines of systemic treatment, including at least one line of ICIs and platinum-based chemotherapy. Participants will be randomized 1:1 to receive either THIO 180 mg per cycle (60 mg IV on Days 1-3 of a 3-week cycle) followed by cemiplimab 350 mg IV on Day 5, or single-agent chemotherapy (vinorelbine, gemcitabine, or docetaxel). The primary endpoint is overall survival (OS). Secondary endpoints include objective response rate (ORR), progression-free survival (PFS) and duration of response (DoR). Current Status: Enrollment is ongoing , preliminary safety data and efficacy outcomes will be assessed through scheduled interim analyses. Conclusion: THIO-104 will provide critical insights into the potential role of telomere-targeting agents in restoring tumor sensitivity to ICIs in NSCLC. The study will also explore key biomarkers to further characterize Ateganosine’s mechanism of action and its potential to predict patient response to therapy. Clinical trial information: 2024-520164-33-00.