Novel Telomere-Targeting Combo Demonstrates Safety in Advanced NSCLC

Combination treatment with THIO (6-thio-2’- deoxyguanosine) and cemiplimab (Libtayo) was generally well tolerated among patients with advanced non–small cell lung cancer (NSCLC), according to a press release on safety lead-in data from part A of the phase 2 THIO-101 trial.

In part B of the phase 2 THIO-101 trial, investigators will randomly assign patients to one of 3 THIO dose levels, including 60 mg, 180 mg, and 360 mg, followed by subsequent cemiplimab every 3 weeks.

In part A of the trial, THIO plus cemiplimab produced no dose-limiting toxicities or significant treatment-related adverse effects (TRAEs). Additionally, investigators reported only mild toxicities including grade 1 fatigue, muscle pain, and 1 event of grade 3 nausea. There were no reported grade 4 AEs.

“Part A’s safety profile is in sharp contrast with the typical safety profile of chemotherapy treatment where 70%-80% of patients [with NSCLC] experience grade 3 and 4 toxicities,” Mihail Obrocea, MD, chief medical officer at MAIA Biotechnology Inc, said in the press release. “Based on the initial safety profile seen at the highest dose in Part A, we are optimistic about the safety profile of THIO.”

THIO is an investigational agent that targets telomeres, which play a role in the survival of cancer cells and their resistance to current therapies. Investigators are developing THIO as a treatment for second and later line NSCLC that has progressed beyond treatment with standard-of-care checkpoint inhibitors.

Investigators of the multi-center, open-label, dose-finding phase 2 THIO-101 trial are evaluating the potential direct anti-cancer and immune system activation effects of THIO administered prior to cemiplimab in patients with advanced NSCLC. In part A, the safety-lead-in portion of the trial, patients received 360 mg or 180 mg of THIO per cycle plus 350 mg of cemiplimab.

In part B, investigators will randomly assign patients to one of 3 THIO dose levels, including 60 mg, 180 mg, and 360 mg, followed by subsequent cemiplimab every 3 weeks. Determining the most efficacious and safe dose of THIO in part B will guide treatment in part C of the trial.

The primary end points of the THIO-101 trial include incidence of dose-limiting toxicities, treatment-emergent AEs, serious AEs, and overall response rate and disease control rate in patients with telomerase-positive disease. Secondary end points include duration of response, progression-free survival, and overall survival.

Patients 18 years and older with histologically or cytologically confirmed stage III or IV NSCLC that has either progressed or relapsed after immune checkpoint inhibitors are eligible for enrollment on the trial. Additional inclusion criteria include having at least 1 measurable lesion per RECIST v1.1 criteria, a life expectancy greater than 12 weeks, an ECOG performance status of 0 or 1, and adequate organ function.

Patients who have unresolved AEs due to agents administered more than 4 weeks prior to beginning study treatment or untreated or symptomatic central nervous system metastases are not able to enroll on the trial. Patients are also unsuitable for enrollment if they had active gastrointestinal bleeding as evidenced by hematemesis or melena, history of another concurrent malignancy for a minimum of 3 years, and significant cardiovascular impairment.

“Recruitment has commenced in the Part B efficacy/dose selection portion of [the phase 2 THIO-101] trial, and we anticipate reporting preliminary efficacy data later this year,” Vlad Vitoc MD, chairman and chief executive officer of MAIA, concluded.

Reference

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, Inc. April 11, 2023. Accessed April 12, 2023. bit.ly/3o2qQfz