Abstract 49P
Background
Despite advancements in first-line treatments, long-term survival for advanced non-small cell lung cancer (NSCLC) remains suboptimal, with only 28% of patients surviving beyond five years. Treatment options for immune checkpoint inhibitor (ICI)-resistant patients are limited. THIO, a telomere-targeting agent, modifies telomeres in cancer cells, including circulating tumor cells (CTCs), confirming its mechanism of action and demonstrating efficacy independent of PD-L1 expression.
Methods
NCT05208944 is a phase II, multicenter, open-label study enrolling advanced NSCLC patients who relapsed after 1–4 prior treatments, including ICIs. CTCs were labeled with TRF1 and γH2AX to detect telomere dysfunction-induced foci (TIFs). Samples from 12 patients treated with THIO (60, 180, or 360 mg) were analyzed at baseline (C1D1) and post-treatment (C1D5). TIF and PDL1 fraction in potential CTCs were measured using flow cytometry and averaged for consistency.
Results
In the thrd line therapy 17 out pf 22 patients (77%) surpassed the benchmark value, and in the 180 mg dose group (n=10) PFS reached 24.1 weeks. Therapeutic responses (partial response or stable disease) occurred regardless of baseline PD-L1 status, underscoring THIO’s efficacy across diverse patient populations. Average IL-6 level at baseline C1D1 was (39.35 pg/mL), C1D5 (62.51 pg/mL), C2D1 (43.35 pg/mL), C2D5 (27.78 pg/mL). Elevated IL-6 levels at C1D5 correlated with responses, highlighting its predictive and mediating role in the immune response to THIO and cemiplimab.
Conclusions
THIO exhibits efficacy in advanced NSCLC 3rd line patients independent of PD-L1 status, with telomere modifications and TIF induction in CTCs. Post-treatment IL-6 elevation correlated with therapeutic response, supporting its utility as a potential predictive biomarker for sequential combination therapy. These findings support THIO sequenced by ICI potential to expand treatment options for ICIresistant NSCLC.
Clinical trial identification
NCT05208944.
Legal entity responsible for the study
MAIA Biotechnology Inc.
Funding
MAIA Biotechnology Inc.
Disclosure
R. Ramlau: Financial Interests, Personal, Advisory Board: Roche, Boehringer Ingelheim, Pfizer, MSD, BMS, Novartis, Takeda, Parexel; Financial Interests, Personal, Invited Speaker: Roche, Boehringer Ingelheim, Novartis, Pfizer, Amgen, BMS, MSD, Merck, AstraZeneca, Parexel, Bioatla Inc, Janssen-Cilag, AstraZeneca, MAIA Biotechnology, Cantargia AB, Shanghai Henlius Biotech, BioNtech SE, Arcus Biosciences Inc. M.D. Cholakova: Financial Interests, Personal, Invited Speaker, Local meeting: Novartis, Eli Lilly, Merck. A.K. Mruk: Financial Interests, Personal, Full or part-time Employment, senior oncologist: Mrukmed Medical Center Rzeszów Poland; Financial Interests, Personal, Full or part-time Employment, Consulting oncologist: Town Hospital Rzeszów; Financial Interests, Personal, Full or part-time Employment, consulting oncologist: Hospital of the Ministry of Internal Affairs Rzeszów Poland; Financial Interests, Institutional, Ownership Interest, co-owner with my wife: Mrukmed Medical Center Rzeszów; Non-Financial Interests, Personal, Principal Investigator, PI in M18-868 trial was carried out in Mrukmed Medical Center: AbbVie Inc; Non-Financial Interests, Personal, Principal Investigator, 6 clinical trials carried out and ongoing in Mrukmed Medical Center: AatraZeneca AB; Non-Financial Interests, Personal, Principal Investigator, Clinical trial AV-951-20-304 carried out in Mrukmed Medical Center: Aveo Pharmaceuticals Pvt, Ltd; Non-Financial Interests, Personal, Principal Investigator, clinical trial XLO92-304 ongoing: Exelixis Inc; Non-Financial Interests, Personal, Principal Investigator, clinical trial WO43919, WO43571, MO39874 carried out in Mrukmed Medical Center: Hoffman-La Roche Ltd; Non-Financial Interests, Personal, Principal Investigator, clinical trial GS-US-577-6153 carried out in Mrukmed Medical Center: Gilead Sciences Inc; Non-Financial Interests, Personal, Principal Investigator, Clinical trial 213831 carried out in Mrukmed Medical Center: GSK Commercial; Non-Financial Interests, Personal, Principal Investigator, G1T38-307 clinical trial carried out in Mrukmed Medical Center: G1 Therapeutics Inc; Non-Financial Interests, Personal, Principal Investigator, THIO-101 clinical trial ongoing in Mrukmed Medical Center: MAJA Biotechnology Inc; Non-Financial Interests, Personal, Principal Investigator, MK-1308A-008 clinical trial ongoing in Mrukmed Medical Center: Merck Sharp & Dohme LLC; Non-Financial Interests, Personal, Principal Investigator, 849-012 clinical trial carried out in Mrukmed Medical Center: MiratiTherapeutics, Inc; Non-Financial Interests, Personal, Principal Investigator, EF-27 Panova-3 clinical trial carried out in Mrukmed Medical Center: Novocure GmbH; Non-Financial Interests, Personal, Principal Investigator, CBYL719H12301, CACZ885V2301 clinical trials carriae out in Mrukmed Medical Center: Novartis Pharma AG; Non-Financial Interests, Personal, Principal Investigator, Lagoon PM1183-C-008-21 clinical trial ongoing Mrukmed Medical Center: Pharma Mar, SA; Non-Financial Interests, Personal, Principal Investigator, R2810-ONC-16113 clinical trial carried out in Mrukmed Medical Center: Regeneron Pharmaceuticals, Inc; Non-Financial Interests, Personal, Principal Investigator, SSGNTUC-029(MOUNTAINEER-03) ongoing Mrukmed Medical Center: Seagen Inc/Pfizer Inc. S. Sótér: Financial Interests, Personal and Institutional, Invited Speaker: Merck, Lilly, AstraZeneca. K. D. Koynov: Financial Interests, Personal, Advisory Board: MSD, Eli Lilly Company, Pfizer, Roche, Bristol Myers Squibb, AstraZeneca, Janssen, Amgen, Astellas; Financial Interests, Personal, Invited Speaker: MSD, Eli Lilly Company, Pfizer, Roche, Bristol Myers Squibb, AstraZeneca, Janssen, Servier, Boehringer Ingelheim, Amgen, Astellas, Bayer, Pierre Fabre, Zentiva, Viatris, Ewopharm, Teva, Merck; Financial Interests, Personal, Invited Speaker, Participation in clinical trials: Roche, MSD, Novartis, AstraZeneca, Amgen, Sanofi; Financial Interests, Personal, Invited Speaker, Participation in clinical trial: Pharma Mar S.A., GSK, MAIA Biotech; Other, Personal, Other, Travel and accommodation expenses: MSD, Roche, Pfizer, Merck. M.R. Girotti: Financial Interests, Personal, Invited Speaker: Roche, Takeda; Financial Interests, Personal, Other, Consultancy: MAIA Biotech; Financial Interests, Personal, Other, Consultant: MAIA Biotech, Biomakers Inc; Financial Interests, Personal, Full or part-time Employment: Accenture; Financial Interests, Personal, Full or part-time Employment, Professor: UADE University. I. Mender: Financial Interests, Institutional, Full or part-time Employment: MAIA Biotechnology; Financial Interests, Institutional, Stocks/Shares: MAIA Biotechnology; Financial Interests, Institutional, Other, named inventor on patent for 6-thio-dG licensed to MAIA Biotechnology.: MAIA Biotechnology. M. Vidotto Mitsunaga: Financial Interests, Personal, Full or part-time Employment, Since January 1, 2024, I’ve been a Director of Business Analytics at MAIA Biotechnology, Inc.: MAIA Biotechnology, Inc.; Financial Interests, Personal, Stocks/Shares, I hold shared of the company stock.: MAIA Biotechnology, Inc. O. Tudos: Financial Interests, Institutional, Full or part-time Employment: MAIA Biotechnology; Financial Interests, Personal, Stocks/Shares: MAIA Biotechnology. M. Failor: Financial Interests, Personal, Full or part-time Employment, Director of Clinical Operations: MAIA Biotech; Non-Financial Interests, Personal, Project Lead: MAIA Biotech; Non-Financial Interests, Personal, Proprietary Information: MAIA Biotech. B. Yao: Financial Interests, Personal, Full or part-time Employment: MAIA Biotechnology; Financial Interests, Personal, Stocks/Shares: MAIA biotechnology. V. Vitoc: Financial Interests, Personal, Officer, Since August 3, 2018, I have been CEO and Chairman of the Board of MAIA Biotechnology, Inc.: MAIA Biotechnology, Inc.; Financial Interests, Personal, Ownership Interest, As found of MAIA Biotechnology, Inc., I hold shares of the company stock.: MAIA Biotechnology, Inc.; Non-Financial Interests, Personal, Member of Board of Directors, I am Chairman of the Board of Directors of MAIA Biotechnology, Inc.: MAIA Biotechnology, Inc.; Non-Financial Interests, Institutional, Product Samples, Clinical Supply Agreement with Regeneron: MAIA Biotechnology, Inc. S. Gryaznov: Financial Interests, Institutional, Full or part-time Employment: Maia Biotechnology; Financial Interests, Institutional, Stocks/Shares: Maia Biotechnology. V. Zaporojan: Financial Interests, Personal, Full or part-time Employment, Sr. Medical Director: MAIA Biotechnology; Financial Interests, Personal, Stocks/Shares: MAIA Biotechnology. All other authors have declared no conflicts of interest.