THIO Sequenced With Cemiplimab Continues to Show Promising Safety in NSCLC

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The first 2 patients with advanced non–small cell lung cancer (NSCLC) dosed with THIO (6-thio-2’-deoxyguanosine) in combination with cemiplimab (Libtayo) continue to be without documented progression for 12.2 and 11.5 months, respectively.¹

The findings are from Part A safety lead-in portion of the ongoing, phase 2 THIO-101 study (NCT05208944), which were announced in a press release by MAIA Biotechnology. Following the end of the study treatment, these 2 patients have remained free of disease progression for 10.2 and 8.5 months, respectively, without requiring any new anti-cancer treatment. Both patients have advanced stage IV metastatic disease and failed 2 prior lines of therapy, including 1 line with an immune checkpoint inhibitor (CPI), and platinum-based chemotherapy.

"We are excited by the observed continued progression-free survival of the first 2 patients following treatment discontinuation, and these results align with our hypothesis that THIO, followed by an immune CPI, can re-sensitize tumors to the CPI and stimulate a potent and long-lasting anti-cancer immune response. This is particularly encouraging given that patients with advanced NSCLC who failed two or more therapy regimens in real-world scenarios have an expected survival of only 3 to 4 months. With therapy, third-line patients generally survive about 6 months; without therapy, survival is only weeks," said Vlad Vitoc, chief executive officer of MAIA, in a press release.

THIO is an investigational telomere-targeting agent in clinical development for the treatment of patients with NSCLC who have progressed beyond the standard-of-care CPI as a second- or later-line option. Telomeres and the enzyme telomerase each play a fundamental role in the survival of cancer cells and their resistance to current therapies. Currently, THIO is being developed as a second- or later- line of treatment for patients with NSCLC who have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

Previously, topline data from part A of the THIO-101 study revealed that patients with NSCLC who were given the combination of THIO and cemiplimab did not generate any dose-limiting toxicities.² Patients enrolled in the study had mild toxicities, including grade 1 fatigue and muscle pain, and 1 case of grade 3 nausea among patients with non–small cell lung cancer. One case of grade 3 nausea was observed; however, no grade 4 adverse events were reported.

The multicenter, open-label, dose finding, phase 2 THIO-101 trial is an ongoing study evaluating THIO in sequential combination with cemiplimab for the treatment of patients with NSCLC. This is the first trial designed to evaluate the potential immune system activation effects of THIO in NSCLC.³

Enrollment is open to patients aged 18 years or older with histologically or cytologically confirmed stage III/IV NSCLC that has progressed or relapsed after treatment with an CPI alone or in combination with chemotherapy. Patients must have at least 1 measurable lesion per RECIST v1.1 criteria, a life expectancy of greater than 12 weeks, an ECOG performance status of 0 or 1, and adequate organ function.

Investigators are assessing whether low doses of THIO administered prior to a checkpoint inhibitor will enhance and prolong immune response in patients with advanced NSCLC who did not respond to treatment previously, or who developed resistance and progressed after first-line treatment regimen containing another checkpoint inhibitor.

The primary end points of the study are to evaluate the safety and tolerability of THIO and overall response rate. Secondary end points of the study include duration of response, progression-free survival, and overall survival, and an exploratory end point of the study is biomarker analysis.

REFERENCES:

MAIA Biotechnology reports updates on preliminary survival data for THIO-101 phase 2 trial for advanced non-small cell lung cancer. News release. MAIA Biotechnology, Inc. July 10, 2023. Accessed July 11, 2023. https://tinyurl.com/4z5jj6ra

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 July 11, 2023. https://bit.ly/43tO7ra

THIO sequenced with cemiplimab in advanced NSCLC. ClinicalTrials.gov. Updated July 8, 2022. Accessed July 11, 2023. https://www.clinicaltrials.gov/ct2/show/NCT05208944