Updated Results Show THIO/Cemiplimab Improves Median OS in Advanced NSCLC

6-thio-2’-deoxyguanosine sequenced plus cemiplimab elicited an OS of 16.9 months in the third-line setting for patients with advanced non–small cell lung cancer.

6-thio-2’-deoxyguanosine (THIO), a first-in-class investigational telomere-targeting agent, when sequenced with cemiplimab (Libtayo) and administered to patients with advanced non–small cell lung cancer (NSCLC) who received at least 2 prior lines of standard of care therapy regimens elicited positive updated results from the pivotal phase 2 THIO-101 trial (NCT05208944), a press release from the developer, Maia Biotechnology, announced.¹

At a data cutoff of January 15, 2025, the median OS was 16.9 months for 22 patients with NSCLC who were in the third line of treatment and received at least 1 dose of THIO in parts A and B of the trial; the lower bound was 12.5 months at a 95% CI and 10.8 months at a 99% CI.¹

Depending on complete results from the ongoing expansion phase of the THIO-101 trial, the developer anticipates an opportunity to achieve accelerated FDA approval.

In November 2024, results from the THIO-101 trial were presented at the 2024 Society for Immunotherapy of Cancer Annual Meeting (SITC).²

THIO-101 is an open-label, multicenter phase 2 trial evaluating whether low doses of THIO then cemiplimab will improve and create enduring responses in patients with advanced NSCLC. It was comprised of 3 parts: part A, the safety lead-in phase with a modified 3 plus 3 design; part B, the randomized, dose-finding, 3-arm Simon’s 2-stage design phase; and, the optional, part C, the high dose arm with a 3 plus 3 design followed by Simon’s 2-stage design if cohort expansion occurs.³

“Treatment with THIO now shows a 99% probability that overall survival [OS] will extend past chemotherapy’s measure by a wide margin,” Vlad Vitoc, MD, chief executive officer of MAIA, stated in the press 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.”

Initially, 10 patients were enrolled in the safety lead-in phase of the trail and received 360 mg of intravenous THIO via 120 mg per day on days 1 to 3 of every 3 weeks and then 350 mg of cemiplimab on day 5 of every 3-week cycle.² In the Simon 2-stage design phase, a total of 79 patients were randomly assigned to receive varying doses of THIO; 24 of whom received 60 mg of THIO, 41 of whom received 180 mg of THIO, and 14 of whom received 360 mg of THIO. The 180 mg dose was chosen as the best dose.

The overall median age was 67 years (range, 45-85); the most common number of prior lines of therapy was 66%; 73% of patients had an ECOG performance status of 1; non-squamous cell carcinoma was observed in 60%; and liver and brain metastases were seen in 15% and 5%, respectively.

Primary trial end points included safety, overall response rate (ORR), and disease control rate. Secondary end points were duration of response, progression-free survival, and OS.

Additionally, patients who received the 180 mg dose in the third line of treatment demonstrated an ORR of 38%.

Regarding safety, the most common treatment-emergent adverse effects (TEAEs) of any grade for patients who received 60 mg (n = 24) were aspartate aminotransferase increased (25%), alanine aminotransferase increased (25%), neutropenia (8.3%), and nausea (8.3%); for 180 mg (n = 41), they were aspartate aminotransferase increased (26.8%), alanine aminotransferase increased (22%), neutropenia (4.9%), and anemia (4.9%); and for 360 mg (n = 14), they were nausea (50%), aspartate transferase increased (28.6%), alanine aminotransferase increased (21.4%), and decreased appetite (14.3%).

The most common TEAEs of grade 3 or higher for patients who received 60 mg were aspartate aminotransferase increased (20.8%), alanine aminotransferase increased (12.5%), and neutropenia (8.3%); for 180 mg, they were alanine aminotransferase increased (9.8%), aspartate transferase increased (4.9%), and neutropenia (2.4%); and for 360 mg, they were alanine transferase increased (14.3%), aspartate aminotransferase increased (14.3%), and nausea (7.1%).

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 5, 2025. https://tinyurl.com/ypuvs8e2
2. Csoszi T, Jankowski T, Urban L, et al. Telomere-targeting agent THIO in sequential combination with cemiplimab demonstrates long term therapeutic benefits beyond treatment cessation. A phase 2 trial in advanced immune checkpoint inhibitor resistant non-small cell lung cancer patients. Presented at: 2024 SITC Annual Meeting; November 6-10, 2024; Houston, TX. Abstract 1492
3. THIO sequenced with cemiplimab in advanced NSCLC. ClinicalTrials.gov. Updated November 22, 2024. Accessed February 5, 2025. https://tinyurl.com/mr3rjuw3