THIO Combo Yields Survival Benefit in Advanced Non–Small Cell Lung Cancer

Investigators hypothesize that THIO may facilitate telomerase-dependent telomeric DNA modification, DNA damage responses, and selective death of cancer cells. Additionally, telomeric fragments that have been damaged by THIO may accumulate in cytosolic micronuclei, thereby activating innate and adaptive T-cell immune responses.

Combining telomere-targeting agent THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) with cemiplimab (Libtayo) demonstrated a survival benefit in a small cohort of patients with advanced non–small cell lung cancer (NSCLC), according to interim findings from the phase 2 THIO-101 trial (NCT05208944).¹

With a data cutoff date of August 1, 2024, 16 patients had a survival follow-up period of more than 12 months, which included 9 patients who received third-line treatment. Among patients who received third-line therapy, the median survival was 10.6 months.

The survival data build upon earlier results related to disease control rate (DCR) and overall response rate (ORR), which developers announced in April 2024.² Among all patients who received third-line treatment, the DCR was 85%. Data also showed that THIO at 180 mg plus cemiplimab produced an ORR of 38%. At the time of the analysis, the median progression-free survival (PFS) in the 180-mg group was 5.5 months, and the 6-month overall survival (OS) rate was 78%.

Full efficacy results from the THIO-101 trial are anticipated for release in late 2024.

“THIO is showing a survival benefit for patients with advanced NSCLC. As our follow-up continues, we have noted that 3 of the earliest patients enrolled are approaching 17-month survival,” Vlad Vitoc, MD, chairman and chief executive officer at MAIA Biotechnology, the developers of THIO, said in the press release on the survival data.¹ “We’re on track to achieve our survival goals in third-line therapy. THIO’s outperformance to date supports our thesis that our telomere targeting agent could become a treatment option for [patients with] advanced NSCLC.”

According to the developers, telomeres may enable cancer cells to survive and demonstrate resistance to currently available therapies. Investigators hypothesize that THIO may facilitate telomerase-dependent telomeric DNA modification, DNA damage responses, and selective death of cancer cells. Additionally, telomeric fragments that have been damaged by THIO may accumulate in cytosolic micronuclei, thereby activating innate and adaptive T-cell immune responses.

Investigators of the multicenter, open-label THIO-101 trial are evaluating whether THIO sequenced before cemiplimab may improve immune responses in patients with advanced NSCLC following progression on frontline therapy containing a checkpoint inhibitor. In addition to THIO at the optimal selected dose of 180 mg, patients received cemiplimab at 350 mg.³

The trial’s primary end points include dose-limiting toxicities, treatment-emergent adverse effects (TEAEs), serious AEs, ORR, and DCR. Secondary end points include duration of response, PFS, and OS.

Patients 18 years and older with histologically confirmed stage III or IV NSCLC that has progressed following prior immune checkpoint inhibitor therapy were eligible for enrollment on the trial. Other eligibility criteria included having 1 or more measurable lesions per RECIST v1.1 guidelines, a life expectancy of at least 12 weeks, an ECOG performance status of 0 or 1, and adequate organ function.

Those with untreated or symptomatic central nervous system metastases or active gastrointestinal bleeding based on hematemesis or melena were unable to enroll on the trial. Having a condition requiring management with corticosteroids and active uncontrolled bacterial, viral, or fungal infections were also grounds for exclusion from the trial.

Developers previously announced safety findings from the THIO-101 trial in July 2024.⁴ As of June 12, 2024, 6 patients were still receiving THIO/cemiplimab following a minimum of 12 months of therapy. Additionally, study treatment appeared to be well tolerated across the trial, with toxicity rates appearing to be lower compared with standard-of-care agents.

References

1. MAIA Biotechnology announces positive survival updates in phase 2 study of THIO in non-small cell lung cancer. News release. MAIA Biotechnology, Inc. September 10, 2024. Accessed September 10, 2024. https://tinyurl.com/2a5faa4r
2. MAIA Biotechnology reveals new clinical data showing THIO’s strong efficacy in non-small cell lung cancer. News release. MAIA Biotechnology, Inc. June 4, 2024. Accessed September 10, 2024. https://tinyurl.com/3yzdaj69
3. THIO sequenced with cemiplimab in advanced NSCLC. ClinicalTrials.gov. Updated August 31, 2023. Accessed September 10, 2024. https://tinyurl.com/3prppmae
4. MAIA Biotechnology announces new updates from phase 2 trial of novel cancer treatment agent. MAIA Biotechnology, Inc. July 23, 2024. Accessed September 10, 2024. https://tinyurl.com/5fd6mdbc