THIO/Cemiplimab Elicits Responses in Advanced NSCLC Cohort

Developers announced that they completed enrollment of patients in the THIO-101 trial early. According to the press release, this study is anticipated to be the first to assess an agent that targets telomere in the field of cancer drug development.

Combining THIO (6-thio-dG) with cemiplimab-rwlc (Libtayo) in the third-line setting produced positive efficacy data among a small cohort of patients with advanced non–small cell lung cancer (NSCLC), according to a press release on findings from the phase 2 THIO-101 trial (NCT05208944).¹

With a data cutoff of January 8, 2024, the study regimen elicited an overall response rate (ORR) of 38% (n = 3/8). Investigators administered THIO at 180 mg plus cemiplimab to patients in the efficacy-evaluable population, which included those who had disease progression following prior therapy with immune checkpoint inhibitors (ICIs).

There were 2 patients who received third-line treatment in the 180-mg dose cohort who did not have recorded scans at the time of the data cutoff. Safety findings in the trial were comparable with prior reports.

Developers announced that they completed enrollment of patients in the THIO-101 trial early. According to the press release, this study is anticipated to be the first to assess an agent that targets telomere in the field of cancer drug development.

“As an impressive measure of efficacy, the strong response rate of 38% in third-line treatment supports our premise that THIO administration prior to cemiplimab can improve tumor responses to immunotherapy in [patients with] advanced NSCLC resistant to [checkpoint inhibitors] and other standard treatments,” Vlad Vitoc, MD, chairman and chief executive officer at MAIA Biotechnology, the developers of THIO-101, said in the press release.¹

Developers previously announced disease control rate (DCR) findings from the THIO-101 trial in October 2023. According to findings presented during a poster session at the 2023 European Society for Medical Oncology Congress (ESMO),THIO plus cemiplimab yielded a DCR of 100% (n = 19/19) as second-line therapy.² Additionally, the DCR was 88% (n = 14/16) for patients who received treatment in the third-line setting and 50% (n = 1/2) for those who received fourth-line therapy.

“In [patients with] NSCLC who received at least one line of therapy, DCRs have shown to be excellent predictors of overall survival [OS]…These exceptional preliminary results underscore our confidence in advancing the trial to bring our novel treatment to [patients with] advanced stage NSCLC,” Vitoc said in a press release on the DCR data.³

In the THIO-101 trial, 123 patients will be assigned to receive THIO at 360 mg, 180 mg, or 60 mg plus cemiplimab every 3 weeks for up to 1 year based on a Simon 2-stage design.²

The trial’s primary end points include dose-limiting toxicities, treatment-emergent adverse effects (AEs), serious AEs, ORR, and DCR.⁴ Secondary end points include duration of response, progression-free survival, and OS.

Patients 18 years and older with histologically or cytologically confirmed stage III or IV NSCLC that has progressed or relapsed following prior treatment with ICIs and 1 or more measurable target lesions based on RECIST v1.1 guidelines are eligible for enrollment on the trial. Additional eligibility criteria include having an ECOG performance status of 0 or 1, a life expectancy of more than 12 weeks, and adequate organ function.

Those who have not recovered from AEs associated with prior treatment or have untreated or symptomatic central nervous system metastases are not able to enroll on the trial. Patients are also unsuitable for enrollment if they have active gastrointestinal bleeding, history of another concurrent malignancy, or significant cardiovascular impairment or a history of myocardial infarction or unstable angina within 6 months prior to study entry.

References

1. MAIA Biotechnology announces strong efficacy of THIO as third-line treatment for non-small cell lung cancer patients. News release. MAIA Biotechnology, Inc. March 6, 2024. Accessed March 7, 2024. https://tinyurl.com/5akc5za9
2. Jankowski T, Soter S, Nagy T, et. al. A phase 2, multi-center, open-label, dose-optimization study evaluating telomere targeting agent THIO sequenced with cemiplimab in patients with advanced NSCLC - preliminary results. Presented at the 2023 European Society for Medical Oncology Congress; October 20-24, 2023; Madrid, Spain. Abstract 1493P.
3. MAIA Biotechnology announces 100% disease control in second-line non-small cell lung cancer demonstrating impressive positive preliminary efficacy data for ongoing THIO-101 phase 2 trial. News release. MAIA Biotechnology, Inc. October 24, 2023. Accessed March 7, 2024. https://tinyurl.com/49ts4y38
4. THIO sequenced with cemiplimab in advanced NSCLC. ClinicalTrials.gov. Accessed March 7, 2024. https://tinyurl.com/3prppmae