THIO Followed by Cemiplimab Shows Early Promise in Advanced NSCLC

The sequential combination of THIO (6-thio-2’-deoxyguanosine) and cemiplimab (Libtayo) provided a progression-free survival (PFS) benefit in the first 2 patients with advanced non–small cell lung cancer (NSCLC) enrolled to the part A safety lead-in portion of the phase 2 THIO-101 trial (NCT05208944).¹

Data showed that these patients, who have advanced stage IV metastatic disease and who have progressed on 2 previous lines of therapy, continue to be alive without documented disease progression for 12.2 months and 11.5 months, respectively, from the start of study treatment. After study treatment was completed, they were noted to be free of disease progression for 10.2 months and 8.5 months, respectively, without needing additional treatment.

Notably, no new safety signals were observed.

“We are excited by the observed continued PFS of the first 2 patients following treatment discontinuation, and these results align with our hypothesis that THIO, followed by an immune checkpoint inhibitor (ICI), can resensitize tumors to the ICI and stimulate a potent and long-lasting anticancer immune response,” Vlad Vitoc, chief executive officer at MAIA Biotechnology, Inc., stated in a press release. “This is particularly encouraging given that patients with advanced NSCLC who failed 2 or more therapy regimens in real-world scenarios have expected survival of only 3 to 4 months. With therapy, third-line patients generally survive about 6 months; without therapy, survival is only weeks.”

THIO is a small molecule that penetrates the blood–brain barrier and has a dual mechanism of action that targets telomeres and has an immunogenic effect.² Preclinical data have indicated that, in vivo, the agent has resulted in complete responses without recurrence in lung cancer, colorectal cancer, liver cancer, melanoma, and brain cancer.

The multicenter, open-label, dose-finding trial is recruiting patients with histologically or cytologically confirmed stage III/IV NSCLC that progressed or relapsed after an ICI alone or plus chemotherapy.³ To be eligible, patients need to be at least 18 years of age, have at least 1 measurable lesion by RECIST v1.1 criteria, an ECOG performance status ranging from 0 to 1, a life expectancy of greater than 12 weeks, and acceptable organ function.

If patients have untreated or symptomatic central nervous system metastases, active gastrointestinal bleeding, are experiencing immune-related adverse effects (AEs) from other agents or have a condition in need of systemic corticosteroids or other immunosuppressive drugs within 2 weeks of study treatment, they will be excluded. Patients also could not have previously required permanent discontinuation of ICIs because of immune-related toxicities.

Part A of the trial utilizes a modified 3+3 design and is comprised of 2 safety lead-in cohorts consisting of 6 patients.⁴ Those in cohort 1 were given THIO at 120 mg on days 1 to 3 every 3 weeks (Q3W), followed by cemiplimab at 350 mg on day 5. For cohort 2, patients were scheduled to receive THIO at 60 mg on days 1 to 3 Q3W followed by cemiplimab at 350 mg on day 5. For part B of the trial, patients will undergo randomization to 20 mg, 60 mg, or 120 mg of THIO on days 1 to 3 Q3W plus cemiplimab at 350 mg on day 5 of each 21-day cycle.³

The primary objectives of the research are to examine the safety and tolerability of THIO as an anticancer drug and as an immune system primer, and to examine the clinical efficacy of THIO in the form of overall response rate.¹

Previous topline data from the part A safety lead-in portion of the trial showed that those who received the combination had mild AEs, including grade 1 fatigue and muscle pain.⁴ One patient experienced nausea that was grade 3 in severity. Notably, no patients experienced a grade 4 event with the regimen.

References

1. 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 10, 2023. https://ir.maiabiotech.com/news-events/press-releases/detail/70/maia-biotechnology-reports-updates-on-preliminary-survival
2. Telomere targeting immunotherapies for cancer. NYSE American: MAIA. April 18, 2023. Accessed July 10, 2023. https://www.sec.gov/Archives/edgar/data/1878313/000156459023005865/maia-fwp.htm
3. THIO sequenced with cemiplimab in advanced NSCLC. ClinicalTrials.gov. Updated July 8, 2022. Accessed July 10, 2023. https://clinicaltrials.gov/study/NCT05208944
4. 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 10, 2023. https://ir.maiabiotech.com/news-events/press-releases/detail/61/maia-biotechnology-reports-positive-topline-data-from-part