Part A of THIO-101 Trial Shows Positive Topline Safety Data in NSCLC

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THIO (6-thio-2’-deoxyguanosine) plus cemiplimab (Libtayo) administered in a sequential combination did generate any dose-limiting toxicities (DLTs) or significant treatment-related adverse events (AEs) among patients with advanced non–small cell lung cancer (NSCLC), according to topline data from the safety lead-in portion, part A, of the phase 2 THIO-101 trial (NCT05208944).¹

THIO is a telomere-targeting agent that is in clinical development for patients with NSCLC who have progressed beyond the standard-of-care immune checkpoint inhibitor as a second- or later-line option. Telomere plays a fundamental role in the survival of cancer cells and their resistance to current therapies.

According to topline data from the study, patients treated with the sequential combination had mild toxicities, including grade 1 fatigue and muscle pain. There was 1 case of grade 3 nausea observed. However, no grade 4 AEs were reported.

“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,” said Mihail Obrocea, MD, chief medical officer of MAIA Biotechnology, in a press 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.”

The phase 2 THIO-101 study is a multicenter, open-label, dose-finding trial designed to assess the potential direct anticancer and immune system activation effects of THIO in patients with NSCLC. Patients enrolled in the trial must be those 18 years of age or older with histologically or cytologically confirmed stage III/IV NSCLC that has progressed or relapsed after treatment with an immune checkpoint inhibitor alone or in combination with chemotherapy. Requirements for enrollment also 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.

In the first part of the trial, part A, a modified 3 + 3 design will be utilized and 2 safety lead-in cohorts each comprised of 6 patients who were assigned to receive THIO followed by cemiplimab were included.² In cohort 1 of part A, patients were given THIO at 120 mg on days 1 to 3 every 3 weeks, which was equal 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 every 3 weeks, followed by the same dose of cemiplimab on day 5.

Then in part B, patients will be randomly assigned to receive 1 of 3 dose levels of THIO followed by cemiplimab. Patients will be given either 20 mg, 60 mg, or 120 mg of THIO on days 1 to 3 every 3 weeks, plus 350 mg of cemiplimab on day 5, during each 21-day cycle.

Incidence of DLTs, treatment-emergent AEs, serious AEs, overall response rate, and disease control rate are the primary end points of the trial. Secondary end points being investigated are duration of response, progression-free survival, and overall survival. An exploratory end point of the study is biomarker analysis.

“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,” said Vlad Vitoc, MD, chief executive officer MAIA Biotechnology, in a press release.¹ “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 12, 2023. https://bit.ly/43tO7ra

2. THIO sequenced with cemiplimab in advanced NSCLC. ClinicalTrials.gov. Updated July 8, 2022. Accessed April 12, 2023. https://www.clinicaltrials.gov/ct2/show/NCT05208944