THIO Followed By Cemiplimab Displays Safety, Tolerability in Advanced NSCLC

The sequential combination of THIO (6-thio-2’-deoxyguanosine) plus cemiplimab (Libtayo) did not lead to any dose-limiting toxicities (DLTs) or significant treatment-related adverse effects (AEs) in patients with advanced non–small cell lung cancer (NSCLC), according to topline data from the part A safety lead-in portion of the phase 2 THIO-101 trial (NCT05208944).¹

Findings showed that patients treated with the sequential combination experienced mild toxicities, such as grade 1 fatigue and muscle pain. One instance of grade 3 nausea was reported; however, no grade 4 AEs occurred.

“Part A’s safety profile is in sharp contrast with the typical safety profile of chemotherapy treatment, where 70% to 80% of [patients with] NSCLC experience grade 3 and 4 toxicities,” Mihail Obrocea, MD, chief medical officer of MAIA Biotechnology, stated in a news release. “The next dose levels of THIO in part B are lower compared to part A. Based on the initial safety profile seen at the highest dose in part A, we are optimistic about the safety profile of THIO.”

THIO targets telomere, which plays a fundamental role in the survival of cancer cells and their resistance to current therapies. THIO is currently under development as a second- or later-line option for patients with NSCLC who have progressed beyond the standard-of-care immune checkpoint inhibitors.

Part A of the trial utilized a modified 3+3 design and included 2 safety lead-in cohorts each comprised of 6 patients who were assigned to receive THIO followed by cemiplimab.2 In part B, patients will be randomly assigned to receive 1 of 3 dose levels of THIO followed by cemiplimab.¹

The ongoing, multicenter, open-label trial is enrolling patients who are at least 18 years of age and have histologically or cytologically confirmed stage III/IV NSCLC that progressed or relapsed following treatment with an immune checkpoint inhibitor alone or in combination with chemotherapy.2 Other key eligibility criteria include having at least 1 measurable lesion per RECIST v1.1 criteria, a life expectancy of more than 12 weeks, an ECOG performance status of 0 or 1, and adequate organ function.

Patients will be excluded from the trial if they have untreated or symptomatic central nervous system metastases, active gastrointestinal bleeding, a condition requiring systemic corticosteroids or other immunosuppressive medications within 14 days of study treatment, ongoing immune-related AEs from other agents, or required permanent discontinuation from prior checkpoint inhibitors due to immune-related AEs.

In part A, patients in cohort 1 received 120 mg of THIO on days 1 to 3 every 3 weeks (Q3W), equating to 360 mg per cycle, followed by 350 mg of cemiplimab on day 5. Those in cohort 2 were scheduled to receive 60 mg of THIO on days 1 to 3 Q3W, followed by the same dose of cemiplimab on day 5.

In part B, patients will receive either 20 mg, 60 mg, or 120 mg of THIO on days 1 to 3 Q3W, plus 350 mg of cemiplimab on day 5, during each 21-day cycle.

The primary end points of the trial are incidence of DLTs, treatment-emergent AEs, and serious AEs, as well as overall response rate and disease control rate. Secondary end points include duration of response, progression-free survival, and overall survival. Biomarker analysis serves as an exploratory end point.

“We are pleased with the completion of the safety lead-in portion, which is a very important milestone and catalyst that marks the continued progression of our phase 2 THIO-101 trial,” Vlad Vitoc, MD, chief executive officer MAIA Biotechnology, stated in a news release. “Recruitment has commenced in the part B efficacy/dose-selection portion of our go-to-market trial, and we anticipate reporting preliminary efficacy data later this year.”

References

1. MAIA Biotechnology reports positive topline data from part A safety lead-in of THIO-101 phase 2 trial for non-small cell lung cancer. News release. MAIA Biotechnology. April 11, 2023. Accessed April 11, 2023. https://ir.maiabiotech.com/news-events/press-releases/detail/
2. THIO sequenced with cemiplimab in advanced NSCLC. ClinicalTrials.gov. Updated July 8, 2022. Accessed April 11, 2023. https://www.clinicaltrials.gov/ct2/show/NCT05208944