Abstract 1193TiP
Background
The modified nucleoside 6-thio-2'-deoxyguanosine (THIO) is a first-in-class direct telomere-targeting agent that is preferentially incorporated in telomeres of telomerase-positive cells, leading to telomere uncapping and cancer cell death. Preclinical evidence indicates that THIO pretreatment sensitizes non-small cell lung cancer (NSCLC) cells to cemiplimab, a PD-1 inhibitor approved as 1L treatment for patients with locally advanced/metastatic NSCLC with ≥50% PD-L1 expression. The THIO-101 trial was designed to evaluate safety and efficacy of THIO followed by cemiplimab in patients with advanced NSCLC who have developed resistance or relapsed after prior immune checkpoint inhibitor (ICI) therapy.
Trial design
THIO-101 will enroll adult patients with stage 3/4 NSCLC, who have progressed or relapsed after treatment with an ICI alone or in combination with platinum-based therapy. Using a modified 3+3 design, the safety lead-in (Part A) will enroll up to 6 patients in the first cohort to receive a total dose of THIO 360 mg IV (120 mg QD, D1–3) followed by a fixed dose of cemiplimab 350 mg on D5 Q3W. If ≥2 patients experience dose-limiting toxicities, a second cohort will receive a total dose of THIO 180 mg IV (60 mg QD, D1-3) followed by cemiplimab. In the dose-finding portion of the study (Part B), patients will be randomized 1:1:1 in a Simon 2-stage design (n=41 per arm) to receive THIO 360 mg [if cleared in Part A], 180 mg, or 60 mg followed by cemiplimab. Sequential THIO and cemiplimab treatment may be continued Q3W for up to 1 year, or until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoints are safety, objective response rate, and disease control rate (CR, PR, and SD). Secondary endpoints include duration of response, progression-free survival, and overall survival; exploratory endpoints include PK/PD parameters and blood biomarkers (IL-6, CRP). Investigators will assess disease progression per RECIST v1.1 and/or iRECIST, with radiographic scans performed on D1 of cycles 3 and 5 and every 9–12 weeks thereafter. Adverse events will be evaluated according to NCI CTCAE v5.0. The trial is enrolling patients at sites in Europe and Australia.
Clinical trial identification
NCT05208944; EudraCT: 2021-005136-34; Protocol, THIO-101 Version 1.0 (release date: 20 October 2021).
Editorial acknowledgement
Medical writing and editorial support were funded by MAIA Biotechnology, Inc. and provided by Melanie Styers, PhD, and Anuradha Kumari, PhD, of BluPrint Oncology Concepts, LLC.
Legal entity responsible for the study
MAIA Biotechnology, Inc.
Funding
MAIA Biotechnology, Inc.
Disclosure
T. Ciuleanu: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Pfizer, Eli Lilly, AstraZeneca, Sanofi, Sandoz, Novartis, Janssen, Astellas, Amgen; Financial Interests, Personal, Advisory Role: Roche, BMS, MSD, Pfizer, Eli Lilly, AstraZeneca, Sanofi, Sandoz, Novartis, Janssen, Astellas, Amgen. R. Joshi: Financial Interests, Personal, Speaker’s Bureau: Gilead, MSD. S. Gryaznov: Financial Interests, Personal, Full or part-time Employment: Maia Biotechnology, Inc., Chicago IL USA; Financial Interests, Personal, Officer, Chief Scientific Officer: Maia Biotechnology, Inc Chicago, IL USA; Financial Interests, Personal, Stocks/Shares: Maia Biotechnology, Inc., Chicago IL USA. V. Vitoc: Financial Interests, Personal, Full or part-time Employment: Maia Biotechnology, Inc., Chicago IL USA; Financial Interests, Personal, Officer, Founder and Chief Executive Officer: Maia Biotechnology, Inc Chicago, IL USA; Financial Interests, Personal, Stocks/Shares: Maia Biotechnology, Inc., Chicago IL USA. M. Obrocea: Financial Interests, Personal, Full or part-time Employment: Maia Biotechnology, Inc., Chicago IL USA; Financial Interests, Personal, Officer, Chief Medical Officer: Maia Biotechnology, Inc Chicago, IL USA; Financial Interests, Personal, Stocks/Shares: Maia Biotechnology, Inc., Chicago IL USA.