THIO Plus Cemiplimab Demonstrates Potential OS Benefit in Pretreated Advanced NSCLC

Treatment with THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) sequenced with cemiplimab-rwlc (Libtayo) showed signals of a survival benefit in patients with advanced non–small cell lung cancer (NSCLC) who received at least 2 prior lines of standard-of-care (SOC) therapy, according to updated data from the phase 2 THIO-101 trial (NCT05208944).1

Findings announced by MAIA Biotechnology showed that patients treated in the third line who received at least 1 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). These outcomes would mark an improvement in OS compared with historical data for SOC therapy in a similar setting, according to MAIA Biotechnology.

Regarding safety, the combination was generally well tolerated.

“Treatment with THIO now shows a 99% probability that OS will extend past chemotherapy’s measure by a wide margin,” Vlad Vitoc, MD, chief executive officer of MAIA Biotechnology, stated in a news release. “THIO’s efficacy in advanced stages of NSCLC continues to exceed our expectations, especially in third-line treatment where the cancer is typically even more resistant to therapy. Our findings suggest great benefits to patients with unmet medical needs who see little hope for the future."

The company also wrote that final results from the ongoing expansion portion of THIO-101 could support an application to the FDA seeking the accelerated approval of THIO.

THIO is a first-in-class investigational designed to target telomeres; telomeres and the enzyme telomerase are pivotal for the survival of cancer cells and their resistance to SOC therapies.

THIO-101 was an open-label, nonrandomized, multicenter, 3-part study that enrolled patients at least 18 years of age with histologically or cytologically confirmed stage III or IV NSCLC that progressed or relapsed after treatment in the advanced setting.2 Notably, patients with stage IV disease were required to have experienced progression or relapsed after first-line treatment. Those with stage III NSCLC needed to have progressed on or been ineligible for local, curative-intent therapy; patients with stage III disease that relapsed or progressed after consolidation therapy with durvalumab (Imfinzi) following definitive chemoradiotherapy were allowed to participate.

An ECOG performance status of 0 or 1 and adequate organ function were also necessary for enrollment.

Patients with untreated or symptomatic central nervous system metastases were excluded; however, those with treated, asymptomatic brain metastasis were eligible. Other key exclusion criteria consisted of active gastrointestinal bleeding; active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy; significant cardiovascular impairment; and ongoing immune-related adverse effects.

Part A of the trial served as a safety lead-in where patients received THIO at 120 mg per day on days 1 to 3 plus cemiplimab at 350 mg on day 5 of each 3-week cycle; or THIO at 180 mg per day on days 1 to 3 plus cemiplimab at 350 mg on day 5 of each 3-week cycle.

In part B, patients received the same cemiplimab regimen plus THIO at 20 mg, 60 mg, or 120 mg per day on days 1 to 3 of each 3-week cycle. Part C of the study examined THIO at 180 mg per day on days 1 to 3 plus cemiplimab at 350 mg on day 5 in each 3-week cycle.

The trial’s primary end points were safety, overall response rate, and disease control rate. Secondary end points included duration of response, progression-free survival, and OS.

References

1. MAIA Biotechnology announces positive efficacy updates for phase 2 THIO-101 trial in advanced non-small cell lung cancer. News release. MAIA Biotechnology. February 4, 2025. Accessed February 4, 2025. https://ir.maiabiotech.com/news-events/press-releases/detail/124/maia-biotechnology-announces-positive-efficacy-updates-for
2. THIO sequenced with cemiplimab in advanced NSCLC. ClinicalTrials.gov. Updated November 11, 2025. Accessed February 4, 2025. https://clinicaltrials.gov/study/NCT05208944