MAIA Biotechnology announced new updates from its Phase 2 THIO-101 clinical trial, evaluating THIO sequenced with Regeneron’s immune checkpoint inhibitor cemiplimab (Libtayo®) in patients with advanced non-small cell lung cancer (NSCLC) who have failed two or more standard-of-care therapy regimens. The data, presented at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting, highlights the potential of THIO-101 to provide long-term therapeutic benefits beyond treatment cessation.
THIO-101: Targeting Telomeres in NSCLC
THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent. Telomeres and telomerase play a crucial role in cancer cell survival and resistance to therapies. THIO induces telomerase-dependent telomeric DNA modification, leading to DNA damage responses and selective cancer cell death. This process activates both innate (cGAS/STING) and adaptive (T-cell) immune responses.
Clinical Trial Results
The THIO-101 trial is a multicenter, open-label, dose-finding Phase 2 clinical trial designed to evaluate THIO’s anti-tumor activity when followed by PD-(L)1 inhibition. As of August 1, 2024, 16 patients in the THIO-101 trial had survival follow-up surpassing 12 months, including 9 in third-line treatment (3L). Interim median survival follow-up in 3L was 10.6 months, compared to the current standard-of-care overall survival of 5.8 months.
Vlad Vitoc, M.D., Chairman and CEO of MAIA, stated, "Our findings to date are particularly significant for advanced-stage patients resistant to CPI and chemotherapy treatments who are in desperate need of new treatment options. In our opinion, the combination of THIO with a CPI is showing promise as a durable and effective NSCLC treatment."
Implications for NSCLC Treatment
The results suggest that THIO-101, when combined with a CPI like cemiplimab, could offer a durable and effective treatment option for NSCLC patients who have progressed after prior checkpoint inhibitor therapy. The trial is testing the hypothesis that low doses of THIO administered prior to cemiplimab will enhance and prolong immune response in patients with advanced NSCLC who previously did not respond or developed resistance after first-line treatment regimen containing another checkpoint inhibitor. The trial design has two primary objectives: (1) to evaluate the safety and tolerability of THIO administered as an anticancer compound and a priming immune activator (2) to assess the clinical efficacy of THIO using Overall Response Rate (ORR) as the primary clinical endpoint.
