MAIA Biotechnology, Inc. has announced positive interim survival data from its Phase 2 THIO-101 trial, evaluating THIO in combination with Regeneron's cemiplimab (Libtayo®) for patients with advanced non-small cell lung cancer (NSCLC) who have progressed after two or more standard-of-care therapies. The results indicate a promising survival benefit, potentially offering a new treatment option for this heavily pre-treated population.
THIO-101 Trial: Survival Outcomes
As of August 1, 2024, the THIO-101 trial data showed that 16 patients had a survival follow-up exceeding 12 months, including 9 patients in the third-line treatment setting. The interim median survival follow-up in the third-line cohort was 10.6 months. This is a notable improvement compared to published data suggesting an overall survival of 5.8 months for third-line NSCLC patients treated with standard-of-care regimens.
Vlad Vitoc, M.D., Chairman and Chief Executive Officer of MAIA Biotechnology, stated, "THIO is showing a survival benefit for patients with advanced NSCLC... We're on track to achieve our survival goals in third-line therapy." He further added that the outperformance of THIO supports the hypothesis that their telomere-targeting agent could become a valuable treatment option for advanced NSCLC.
Mechanism of Action and Prior Efficacy Data
THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent. Telomeres, along with the enzyme telomerase, are crucial for the survival and resistance of cancer cells. THIO induces telomerase-dependent telomeric DNA modification, leading to DNA damage responses and selective cancer cell death. The damaged telomeric fragments can also activate both innate (cGAS/STING) and adaptive (T-cell) immune responses.
Previous data from the THIO-101 trial, announced in April 2024, demonstrated an overall response rate (ORR) of 38%, a disease control rate (DCR) of 88%, and a median progression-free survival (PFS) of 5.5 months with THIO 180mg + CPI in the third-line setting.
Trial Design and Patient Population
The THIO-101 trial is a multicenter, open-label, dose-finding Phase 2 study. It is designed to evaluate the anti-tumor activity of THIO when followed by PD-(L)1 inhibition with cemiplimab (Libtayo®). 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 containing a checkpoint inhibitor.
The trial's primary objectives are to evaluate the safety and tolerability of THIO and to assess its clinical efficacy using Overall Response Rate (ORR) as the primary clinical endpoint. Key inclusion criteria include patients 18 years and older with histologically confirmed stage III or IV NSCLC that has progressed following prior immune checkpoint inhibitor therapy.
Implications for NSCLC Treatment
These interim results suggest that THIO, in combination with cemiplimab, may offer a clinically meaningful benefit for patients with advanced NSCLC who have limited treatment options. The full efficacy results of the THIO-101 trial are expected later this year and will provide further insights into the potential of this novel therapeutic approach.
