Updated data from the phase 2 THIO-101 trial indicates that treatment with THIO (6-thio-dG) sequenced with cemiplimab (Libtayo) demonstrates a potential overall survival (OS) benefit in patients with advanced non-small cell lung cancer (NSCLC) who have received at least two prior lines of standard-of-care (SOC) therapy. The findings, announced by MAIA Biotechnology, suggest a significant improvement in OS compared to historical data for SOC therapy in a similar setting.
Promising Efficacy in Heavily Pretreated NSCLC
In the trial, patients treated in the third-line setting who received at least one dose of THIO (n = 22) experienced a median overall survival (OS) of 16.9 months (lower bound of the 95% CI, 12.5 months; lower bound of the 99% CI, 10.8 months). Vlad Vitoc, MD, chief executive officer of MAIA Biotechnology, stated that THIO now shows a 99% probability of extending OS past chemotherapy's measure by a wide margin. He also noted that THIO's efficacy in advanced stages of NSCLC continues to exceed expectations, especially in third-line treatment where the cancer is typically more resistant to therapy.
Safety and Tolerability
The combination of THIO and cemiplimab was generally well-tolerated. Most adverse effects (AEs) were grade 1 or 2, and no dose-limiting toxicities were reported during the safety lead-in. In the overall population, common treatment-emergent AEs (TEAEs) included increased aspartate aminotransferase (AST; 26.6%), increased alanine aminotransferase (ALT; 22.8%), nausea (12.7%), and neutropenia (5.1%).
Trial Design and Endpoints
THIO-101 is an open-label, nonrandomized, multicenter, three-part study. It enrolled patients aged 18 years and older with histologically or cytologically confirmed stage III or IV NSCLC that had progressed or relapsed after treatment in the advanced setting. The trial's primary endpoints were safety, overall response rate (ORR), and disease control rate (DCR). Secondary endpoints included duration of response, progression-free survival (PFS), and OS.
Mechanism of Action and Potential for Accelerated Approval
THIO is a first-in-class investigational agent designed to target telomeres, which, along with the enzyme telomerase, are critical for the survival of cancer cells and their resistance to SOC therapies. MAIA Biotechnology indicated that final results from the ongoing expansion portion of THIO-101 could support an application to the FDA seeking accelerated approval of THIO.
Additional Data from SITC 2024
Data presented at the 2024 Society for Immunotherapy of Cancer Annual Meeting (SITC) showed enduring activity among patients with advanced checkpoint inhibitor-resistant NSCLC who received THIO plus cemiplimab. Among evaluable patients who completed at least one post-baseline assessment (n = 69), nine experienced partial responses (PRs) per RECIST 1.1, and seven achieved confirmed PRs via a second scan per investigator assessment. Patients treated in the third-line setting (n = 20) achieved a disease control rate (DCR) of 85%.
