1493P - A phase II, multi-center, open-label, dose-optimization study evaluating telomere targeting agent THIO sequenced with cemiplimab in patients with advanced NSCLC: Preliminary results

Background

THIO (6-thio-2'-deoxyguanosine) is a small molecule, first-in class direct cancer telomere targeting agent which selectively targets telomerase positive (TERT+) cancer cells. It is incorporated de novo in synthesized telomeres leading to chromatin uncapping, DNA damage signals generation and rapid apoptosis. Preclinical data in NSCLC indicates that low doses of THIO induce sensitivity to immune check point inhibitors (ICIs) when administered prior to an ICI.

Methods

This is a phase 2, dose-optimization clinical study in adults with advanced NSCLC who either progressed or relapsed after 1L treatment with ICI alone or in combination with chemotherapy. Using a modified 3+3 design, the safety lead-in (Part A) enrolled 10 patients who received THIO, 360 mg IV [120 mg QD, D1–3], followed by 350 mg cemiplimab on D5, Q3W. The primary endpoints are safety, ORR, DCR. Once the safety of the 360 mg is characterized, additional patients are randomized in the dose-finding portion of the study (Part B). Using a Simon 2-stage design, a total of 123 patients (41 patients/arm) will be assigned to one of the THIO doses: 360, 180, or 60 mg followed by cemiplimab Q3W for up to 1 year. Disease status is assessed at 6-week intervals through cycle 5 and every 9 -12 weeks thereafter.

Results

As of April 2023, 13 patients received at least one dose of THIO followed by cemiplimab (10 in Part A and 3 in Part B). All patients had 1-3 prior treatments and had documented disease progression. In Part A, no DLTs were reported (n = 10 subjects, 9 evaluable and 1 replaced due to delayed toxicities from a previous treatment). Most AEs were G1; G3 anemia in 1 patient (8%); G3 nausea, G3 AST/ALT elevations reported in 2 patients (15%) and one death not treatment related; 29 cycles were administered, and 4 patients had at least one radiographic evaluation after 2 cycles. The first 2 patients enrolled were discontinued after 5 and 4 cycles respectively due to withdrawal of consent and delayed recovery of toxicities; they are alive and progression-free with no new treatment at 10- and 9-months follow-up.

Conclusions

The study continues patient enrollment at all 3 dose-levels.

Clinical trial identification

NCT05208944; Release date: 15 January 2023.

Editorial acknowledgement

Legal entity responsible for the study

MAIA Biotechnology, Inc.

Funding

MAIA Biotechnology.

Disclosure

All authors have declared no conflicts of interest.