Patients with advanced non-small cell lung cancer (NSCLC) that is resistant to checkpoint inhibitors saw benefits from treatment with THIO (6-thio-2’-deoxyguanosine; 6-thio-dG) in combination with Libtayo (cemiplimab), researchers have reported.
Findings from the phase 2 THIO-101 clinical trial were presented during the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting.
At the data cutoff on Sept. 16, 2024, among 69 evaluable patients who completed at least one post-baseline assessment, nine experienced partial responses (PRs) and seven achieved confirmed PRs via a second scan. Nineteen patients had survival follow-ups exceeding 12 months; all nine patients in the second line of therapy were ongoing follow-ups, eight of 10 patients in the third line were ongoing follow-ups and one patient had received 25 cycles of therapy.
Patients treated in the third-line setting (20 patients) achieved a disease control rate (DCR) of 85%. At a median survival follow-up of 11.5 months, 70% of these patients crossed the 5.8-month overall survival (OS) threshold and 85% crossed the 2.5-month progression-free survival (PFS) threshold.
Glossary
Disease control rate (DCR): patients who had a complete response, partial response or stable disease from treatment.
Overall survival (OS): the time a patient lives, regardless of disease status.
Progression-free survival (PFS): the time a patient lives without their disease spreading or worsening.
Objective response rate (ORR): patients whose disease responded partially or completely to treatment.
Increased aspartate aminotransferase (AST): elevated enzymes that indicate liver damage.
Increased alanine aminotransferase (ALT): elevated enzymes that indicate liver damage or disease.
Neutropenia: decreased levels of neutrophils, a type of white blood cell.
Additionally, eight patients who received THIO at a dose of 180 milligrams (mg) plus Libtayo in the third line of therapy experienced an objective response rate (ORR) of 38%. At a median survival follow-up of 11.4 months, the median PFS was 5.5 months, 75% of patients crossed the 5.8-month OS threshold and 88% crossed the 2.5-month PFS threshold. The 6-month OS rate was 75%.
“This regimen demonstrated an ORR of 38% in the selected 180-mg dose, significantly surpassing the approximately 6% [ORR] seen with standard therapies in a heavily pretreated population,” Dr. Victor Zaporojan, the senior medical director of MAIA Biotechnology, said during the presentation. “The THIO and [Libtayo] combination not only offers a durable and effective treatment for advanced NSCLC but also [has the] potential to redefine standard care [with] promising response rates and extended survival benefits.”
THIO was granted orphan drug designation from the FDA in April 2022 for the treatment of patients with hepatocellular carcinoma. In August 2022, the agent also received orphan drug designation from the FDA in small cell lung cancer.
READ MORE: THIO-Libtayo Regimen Is ‘Encouraging’ for Relapsed NSCLC
THIO-101 was an open-label, multicenter study that enrolled adult patients with advanced NSCLC who experienced disease progression or relapse following treatment with an immune checkpoint inhibitor in the first or second line of therapy.
In terms of safety, treatment with THIO plus Libtayo was generally well-tolerated and most side effects were grade 1 (mild) or 2 (moderate); no dose-limiting toxicities were reported during the safety lead-in. In the overall population, any-grade treatment-emergent side effects occurring in at least two patients included increased aspartate aminotransferase (AST; 26.6%), increased alanine aminotransferase (ALT; 22.8%), nausea (12.7%) and neutropenia (5.1%).
Grade 3 (severe) or higher treatment-emergent side effects included increased ALT (11.4%), increased AST (11.4%) and neutropenia (3.8%). Enrollment into the 360-mg group was paused following an instance of grade 4 (life-threatening) liver function test elevation.
In November 2023, the 180-mg dose level of THIO was selected as the best dose. Part B of the study is evaluating THIO at this dose and completed enrollment in February 2024.
Reference
“Telomere-targeting agent THIO in sequential combination with cemiplimab demonstrates long term therapeutic benefits beyond treatment cessation. A phase 2 trial in advanced immune checkpoint inhibitor resistant non-small cell lung cancer patients,” by Dr. Tibor Csoszi, et al., presented at 2024 SITC Annual Meeting.
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