MAIA Biotechnology, Inc. is set to initiate a Phase 3 pivotal trial, named THIO-104, in 2025 to evaluate the efficacy of THIO when administered in sequence with a checkpoint inhibitor (CPI) for third-line non-small cell lung cancer (NSCLC) patients who have developed resistance to both checkpoint inhibitors and chemotherapy. This advancement follows promising results from the THIO-101 Phase 2 trial. The study is designed as a multicenter, open-label trial that will directly compare the THIO sequence with CPI to chemotherapy through a 1:1 randomization of up to 300 patients across select sites in Asia, Europe, and the U.S.
The THIO-104 trial's primary endpoint is overall survival. Secondary endpoints include disease control rate, overall response rate, duration of response, progression-free survival, and safety. These measures will provide a comprehensive assessment of THIO's clinical benefit in this patient population.
THIO: A Novel Telomere-Targeting Agent
THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) represents a novel approach to cancer therapy as a first-in-class investigational telomere-targeting agent. Telomeres and the enzyme telomerase are critical for the survival and therapy resistance of cancer cells. THIO functions by inducing telomerase-dependent telomeric DNA modification, triggering DNA damage responses, and selectively inducing cancer cell death. The accumulation of THIO-damaged telomeric fragments in cytosolic micronuclei activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. Preclinical models have demonstrated that sequential treatment with THIO followed by PD-(L)1 inhibitors leads to significant and sustained tumor regression through the induction of cancer type-specific immune memory.
Clinical Development and Future Prospects
Currently, THIO is being developed as a third-line treatment for NSCLC patients who have become resistant to checkpoint inhibitors and chemotherapy. Vlad Vitoc, M.D., CEO of MAIA, stated, "THIO has consistently and substantially outperformed standard treatment options in our THIO-101 Phase 2 trial to date. THIO-104 will give us direct comparative data from a randomized study in patients in the third line of treatment," He added, "We expect that the results from this study will further illuminate THIO’s unmatched benefits for advanced-stage NSCLC patients and that the initiation of THIO-104 will mark an important milestone along our goal for THIO’s FDA commercial approval."
