MAIA Biotechnology, Inc. (NYSE American: MAIA) has announced the completion of enrollment in its Phase 2 THIO-101 clinical trial. This trial is evaluating THIO, a telomere-targeting agent, in sequence with the immune checkpoint inhibitor cemiplimab (Libtayo®) for patients with advanced non-small cell lung cancer (NSCLC). The completion of enrollment marks a significant milestone in the development of this novel cancer therapy.
The trial reached its enrollment target of 41 patients for the 180mg/dose cohort on February 19, 2024. Prior to this, 79 patients had received either 60mg (24 patients), 180mg (41 patients) or 360mg (14 patients). The original trial design aimed for up to 182 patients, including those in the safety lead-in and 41 patients in each of the three tested doses (60mg, 180mg, and 360mg). Following the selection of 180 mg/cycle as the optimal dose in December 2023, enrollment was focused on this dose, leading to early completion.
Rationale for THIO-101
The THIO-101 trial is designed to assess the safety, tolerability, and preliminary clinical efficacy of THIO in patients with advanced NSCLC who have progressed or relapsed after initial treatment with an immune checkpoint inhibitor, either alone or in combination with chemotherapy. NSCLC remains a significant challenge, with many patients developing resistance to first-line therapies, creating an unmet need for effective second-line treatments.
Mechanism of Action
THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent. Telomeres and telomerase play a crucial role in the survival and resistance of cancer cells. THIO induces telomerase-dependent telomeric DNA modification, leading to DNA damage responses and selective 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 studies have demonstrated that sequential treatment with THIO followed by PD-(L)1 inhibitors results in significant and lasting tumor regression in advanced cancer models by inducing cancer type–specific immune memory.
Trial Design and Objectives
THIO-101 is a multicenter, open-label, dose-finding Phase 2 clinical trial. It is designed to evaluate THIO's anti-tumor activity when followed by PD-(L)1 inhibition. The trial is based on the hypothesis that low doses of THIO administered prior to cemiplimab (Libtayo®) will enhance and prolong immune response in patients with advanced NSCLC who previously did not respond or developed resistance after first-line treatment containing another checkpoint inhibitor. The primary objectives are to evaluate the safety and tolerability of THIO as an anticancer compound and a priming immune activator, and to assess the clinical efficacy of THIO using Overall Response Rate (ORR) as the primary clinical endpoint.
Management Commentary
"Enrollment in our Phase 2 THIO-101 trial has been strong from the start. With excellent results across all doses and our selection of the optimal dose in December 2023, we enrolled the necessary number of patients in the Simon 2-stage design to achieve our trial endpoints earlier than expected," said Vlad Vitoc, M.D., MAIA’s Chairman and Chief Executive Officer. "THIO-101 preliminary data has demonstrated unprecedented rates of disease control and response to date, and we look forward to the long-term efficacy results as we continue to monitor the enrolled patients in the upcoming months. As the only direct telomere targeting agent currently undergoing clinical development in the field of cancer, we believe THIO holds a time-to-market advantage and strong potential to become a new standard of care for NSCLC."
Future Development
MAIA Biotechnology is also exploring additional indications and developing a pipeline of next-generation THIO-like molecules. More than 80 THIO-like compounds have been developed for the Company’s second-generation telomere targeting program. The company's pipeline includes THIO-102 Phase 2 and THIO-103 Phase 2/3 clinical trials (planning stage), and Investigational New Drug (IND)-enabling studies for second-generation telomere targeting agents. Topline data from the THIO-101 trial is expected in the second half of 2024.
