Phase 2 study of telomere-targeting agent THIO sequenced with cemiplimab in third-line immune checkpoint inhibitor–resistant advanced NSCLC: Evaluation of overall survival (OS).

8585 Background: Despite advancements in third line treatments, long-term survival for advanced non-small cell lung cancer (NSCLC) remains suboptimal, with median survival follow-up of only 5.8 months. 1 Among patients treated with prior platinum chemotherapy and immune checkpoint inhibitors (ICIs), the median survival was reported to be 6.47 months 2 . Treatment options for ICI-resistant patients are limited. THIO, a telomere-targeting agent that modifies telomeres in cancer cells, demonstrates improved overall survival (OS) independent of PD-L1 expression. Methods: NCT05208944 is a phase 2, multicenter, open-label study that enrolled 79 patients with advanced NSCLC who relapsed after 1–4 prior treatments, including ICIs. In the third line therapy 22 patients treated with THIO (60, 180, or 360 mg) were evaluated for OS and their prior PD-L1 expression at the time of study enrollment (C1D1). Results: In the third line therapy 22 patients have a current median survival follow-up of 13 months which significantly surpassed the benchmark value, and in the 180 mg dose group (n=10) it reached 16.9 months compared to 5.8 months for the benchmark. 1 THIO followed by cemiplimab was generally well tolerated in this difficult-to-treat population. The response to THIO and cemiplimab, demonstrated by partial response (PR) and stable disease (SD) was independent of baseline PD-L1 status. This indicates that THIO can be effective across patients regardless of their PD-L1 status. Conclusion: THIO demonstrates clinically meaningful OS improvement in third line patients with advanced NSCLC, independent of PD-L1 status. The improved OS observed in patients treated with THIO in sequential combination with an ICI, compared to standard chemotherapy, supports its potential to expand treatment options for ICI-resistant advanced NSCLC. Clinical trial information: NCT05208944 .