Sequential Treatment With Telomere-Targeted Therapy, Checkpoint Inhibition Produces High DCR in NSCLC

Treatment with the first-in-class telomere-targeting agent THIO followed by cemiplimab-rwlc (Libtayo) led to a high disease control rate (DCR) regardless of dose level in patients with pretreated non–small cell lung cancer (NSCLC), meeting the predetermined statistical significance thresholds required of the phase 2 THIO-101 trial (NCT05208944) before proceeding to the next phase.¹

In updated interim data, which were evaluated with a data cutoff of November 13, 2023, 60 patients had received study therapy and 42 had at least 1 postbaseline assessment. Among those who received either 60 mg, 180 mg, or 360 mg of THIO plus cemiplimab, the DCR was 100% in the second line and 88% in the third line. Based on efficacy, 180 mg was selected as the dose for continued evaluation.

“We are entering 2024 with strong momentum and great excitement about our programs and pipeline,” Vlad Vitoc, MD, chairman and chief executive officer of MAIA, stated in a news release. “To date, preliminary phase 2 data on THIO in NSCLC has demonstrated unprecedented rates of disease control and response—measures that vastly outperform the standard of care.”

As a telomere-targeted agent, THIO is designed to lead to telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. Following the accumulation of THIO-damaged telomeric fragments in cytosolic micronuclei, innate cGAS/STING and adaptive T-cell immune responses are activated. When coupled with sequential treatment with PD-(L)1 inhibitors, THIO has shown substantial tumor regression in advanced in vivo cancer models through cancer-type–specific immune memory.

Previously, the FDA gave the green light to the investigational new drug application for THIO to be evaluated in THIO-101, a multicenter, open-label, 3-part, dose-finding trial. The trial is the first to evaluate the agent’s efficacy prior to PD-(L)1 inhibition.

To be eligible for enrollment, patients have to be at least 18 years of age and have received a diagnosis of stage III or IV NSCLC that has progressed or relapsed after checkpoint inhibition, as defined by the SITC Immunotherapy Resistance Task Force.²

Part A consists of a modified 3+3 design in which up to 2 safety lead-in cohorts comprised of 6 patients each are given sequential treatment with THIO and cemiplimab. In each part, patients will receive 350 mg of cemiplimab on day 5.

The coprimary objectives of the trial are to determine the safety and tolerability of THIO as an antineoplastic therapy and as a priming immune activator, and to assess the efficacy of the agent in the form of objective response rate and DCR. Secondary end points include duration of response, progression-free survival, and overall survival. Biomarkers will be evaluated in an exploratory analysis.^1,2 

To date, the treatment regimen has proven safe and generally well tolerated in a heavily pretreated population.¹

“In addition to NSCLC, our pipeline of immuno-oncology therapies includes THIO orphan drug designations for multiple hard-to-treat cancers, and our research includes THIO-like second-generation telomere-targeting agents,” Vitoc added in the press release. “The main objective for the second-generation program is to discover new compounds with potentially improved specificity toward cancer cells relative to normal cells and with potentially increased anticancer activity.”

Several milestones are on target for 2024 as enrollment to THIO-101 continues, including long-term efficacy, Vitoc concluded.

References

1. Maia Biotechnology provides positive phase 2 clinical updates for lead anticancer agent and outlines targeted milestones for 2024. News release. MAIA Biotechnology. January 17, 2024. Accessed January 18, 2024. https://ir.maiabiotech.com/news-events/press-releases/detail/88/maia-biotechnology-provides-positive-phase-2-clinical
2. THIO sequenced with cemiplimab in advanced NSCLC. ClinicalTrials.gov. Updated August 31, 2023. Accessed January 18, 2024. https://clinicaltrials.gov/study/NCT05208944