Ateganosine Plus Cemiplimab Extends PFS Beyond Standard of Care in NSCLC Trial

Updated efficacy data from the phase 2 THIO-101 trial (NCT05208944) evaluating ateganosine (THIO;6-thio-2’-deoxyguanosine) combined with the immune checkpoint inhibitor (ICI) cemiplimab (Libtayo) as third-line treatment for advanced non–small cell lung cancer (NSCLC) illustrates a continuing positive trend, this time in its secondary end point of progression-free survival (PFS).¹

As of the data cutoff on June 30, 2025, the median PFS in the third-line treatment dose of 180 mg was estimated at 5.6 months, a sizable increase compared with the PFS seen in current standard-of-care regimens of 2.5 months. The median overall survival (OS) was 17.8 months. These data were presented during the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer.^1,2

“THIO-101 continues to reveal impressive efficacy with observed [PFS] of 5.6 months, which is more than double the standard of care PFS of just 2.5 months. The data also demonstrate the durability of ateganosine treatment through extended treatment cycles, which is in line with consistent tolerability and low toxicity,” said Vlad Vitoc, MD, chairman and chief executive officer of MAIA Biotechnology, in a press release.¹

The pattern of surpassing standard-of-care efficacy is also evident in previous phase 2 THIO-101 data which demonstrated promising performance in its primary end point with an overall response rate (ORR) of 38%, exceeding the ORR seen in current standard of care. Additionally, the combination showed durable clinical activity in patients with ICI-resistant NSCLC, with partial responses occurring in 10 patients.

What Is the Phase 2 THIO-101 Trial Evaluating?

THIO-101 is an actively recruiting, phase 2, open-label, multicenter study ongoing in 33 sites globally.³ It evaluates ateganosine plus cemiplimab in adult patients with advanced NSCLC whose disease had failed 2 or more prior standard-of-care treatment regimens. The study consists of 3 parts: a safety lead-in (part A), a dose-finding portion (part B), and an expansion trial comparing the performance of the combination therapy against ateganosine monotherapy (part C). Patients are eligible to participate if they have stage 3 or 4 histologically or cytologically confirmed NSCLC that has progressed or relapsed after 1 to 4 prior treatment lines and have secondary resistance to an ICI.³

The study’s primary end points include ORR, disease control rate, and safety; secondary end points include PFS, OS, and duration of response.

What Unmet Need Does Ateganosine Address?

NSCLC accounts for 85% of lung cancer cases globally.⁴ Despite its high prevalence, advances in first-line treatment have thus far failed to address the disease’s poor prognosis, in part due to lack of treatment options available to overcome ICI resistance.²

Ateganosine seeks to address ICI resistance by targeting telomeres, a prime target in cancer cell survival and resistance.¹ The agent is an investigational small molecule³ being developed as a second or later line of treatment after standard-of-care regimens prove ineffective.

What Are the Next Steps in Clinical Development?

Previously, the FDA granted ateganosine fast track designation. This designation will expedite clinical development and potentially set ateganosine on a path to accelerated approval, given sustained positive results.

The part C phase 2 THIO-101 expansion trial is also underway, which began enrolling patients in July 2025.¹ While parts A and B have yielded promising results, part C will further validate these findings by evaluating ateganosine as a monotherapy against the combination regimen in up to 48 patients.^2,5

REFERENCES:

1. MAIA Biotechnology Highlights Positive Efficacy Data from THIO-101 Phase 2 Clinical Trial in Non–Small Cell Lung Cancer. News release. MAIA Biotechnology. Published September 11, 2025. Accessed September 15, 2025. https://tinyurl.com/bdhznhxs

2. Jankowski T, Kowal-Rosinska M, Csõszi T, et al. Study of THIO Sequenced with Cemiplimab in 3rd Line Immune Checkpoint Inhibitor-resistant aNSCLC: Improvement in PFS. Presented at: International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer; September 5–9, 2025; Barcelona, Spain. https://tinyurl.com/pjhetrfa

3. THIO Sequenced With Cemiplimab in Advanced NSCLC. ClinicalTrials.gov. Updated May 31, 2025. Accessed September 16, 2025. https://clinicaltrials.gov/study/NCT05208944

4. Wang K, Leyba A, Hsu R. Addressing the unmet need in NSCLC progression with advances in second-line therapeutics. ETAT. 2024;5(6):1297-1320. doi:https://doi.org/10.37349/etat.2024.00277

5. MAIA Biotechnology Announces Design for Expansion of THIO-101 Phase 2 Trial in Advanced Non–Small Lung Cancer. News release. MAIA Biotechnology. Published February 26, 2025. Accessed September 16, 2025. https://tinyurl.com/wwvuawua