Ateganosine Sequenced With Cemiplimab Displays Activity in Pretreated NSCLC

The investigational telomere-targeting agent ateganosine (THIO) sequenced with cemiplimab (Libtayo) produced positive efficacy data in patients with advanced non–small cell lung cancer (NSCLC) who experienced disease progression following at least 2 standard-of-care (SOC) regimens, according to data from the phase 2 THIO-101 trial (NCT05208944).¹

At the June 30, 2025, data cutoff, findings from THIO-101 presented in a poster during the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer demonstrated that evaluable patients who received ateganosine at 180 mg as a third-line treatment (n = 10) achieved an estimated median progression-free survival (PFS) of 5.6 months.² Additionally, the estimated median overall survival (OS) was 17.8 months with a 95% CI lower bound of 12.5 months among patients who received ateganosine in the third-line setting across all dose levels (n = 22).

“THIO-101 continues to reveal impressive efficacy with an observed [median] PFS of 5.6 months, which is more than double the SOC 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,” Vlad Vitoc, MD, MBA, the chairman and chief executive officer of MAIA Biotechnology, stated in a news release.¹ “We are seeking further validation of ateganosine’s strong efficacy in our THIO-101 phase 2 expansion trial, which began enrolling patients in July 2025.”

What Is the Design of the THIO-101 Trial?

THIO-101 is an ongoing, open-label, multicenter study of ateganosine sequenced with cemiplimab in adult patients with advanced NSCLC who experienced disease progression or relapse follow 1 to 4 previous lines of treatment, including frontline immune checkpoint inhibitor (ICI) therapy alone or in combination with platinum-based chemotherapy.^2,3 Patients were required to have stage III or IV disease, secondary resistance to the prior ICI, no prior targeted therapy for driver mutations, at least 1 measurable target lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and adequate organ function.³

Part A of the trial followed a modified 3+3 design and enrolled 10 patients who received ateganosine at 120 mg on days 1 through 3 every 3 weeks sequenced with cemiplimab at 350 mg on day 5.² In part B, 79 patients were randomly assigned to receive ateganosine at 60 mg, 180 mg, or 360 mg per cycle, all sequenced with cemiplimab. The best dose of ateganosine was identified as 180 mg, and enrollment to parts A and B was completed in February 2024.

An expansion cohort based on the data from part B commenced enrollment in July 2025.² In part C of the expansion cohort, up to 48 patients will be randomly assigned to receive ateganosine plus cemiplimab or ateganosine monotherapy. Part D is planned to be a single-arm efficacy cohort evaluating ateganosine sequenced with cemiplimab as a third-line treatment for a planned 100 patients with advanced/metastatic NSCLC.³

The primary end points assessed in the present analysis were safety, overall response rate (ORR), and disease control rate (DCR).² Secondary end points included PFS, OS, and duration of response. Pharmacokinetics and pharmacodynamics were also assessed as exploratory end points.

What Is the Safety Profile of Ateganosine Plus Cemiplimab?

The study authors noted that ateganosine plus cemiplimab was generally well tolerated, and most adverse effects (AEs) were grade 1 to 2 in severity. No dose-limiting toxicities were reported during the part A safety lead-in portion. The most common any-grade treatment-emergent AEs (TEAEs) among patients treated across all dose levels (n = 79) included increased aspartate aminotransferase (AST) levels (27%), increased alanine aminotransferase (ALT) levels (23%), nausea (13%), anemia (11%), hyponatremia (10%), and weight decrease (10%). Grade 3 or higher treatment-related TEAEs included increased ALT (11.4%) and AST (11.4%) levels, as well as neutropenia (3.8%).

What Were the Key Response Data With the Combination?

Among the 79 patients who received at least 1 dose of ateganosine, partial responses per RECIST 1.1 criteria were reported in 10 patients (6 in the second-line and 4 in the third-line settings). Thirteen patients remained on treatment or were in ongoing follow-up.

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. September 11, 2025. Accessed September 11, 2025. https://ir.maiabiotech.com/news-events/press-releases/detail/150/maia-biotechnology-highlights-positive-efficacy-data-from
2. Jankowski T, Kowal-Rosinska, Csoszi 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 2025 World Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain. Abstract P1.11.82.
3. THIO sequenced with cemiplimab in advanced NSCLC. ClinicalTrials.gov. Updated May 31, 2025. Accessed September 11, 2025. https://clinicaltrials.gov/study/NCT05208944