THIO Sequenced With Cemiplimab in Advanced NSCLC

NCT05208944 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: THIO-1012023-504595-26-002021-005136-34
• Study Type: interventional
• Target: 227
• Locations: 7 countries
• Sites: 35

Brief Summary

THIO is a first-in-class small molecule telomere targeting agent, in development for the treatment of non-small cell lung cancer (NSCLC) in combination with cemiplimab (LIBTAYO®). THIO is preferentially incorporated into telomeres sequence in telomerase-positive cells leading to rapid telomere uncapping, genomic instability, and cell death. Cemiplimab is a programmed cell death protein 1 (PD-1) inhibitor recently approved as a first-line treatment for patients with locally advanced or metastatic NSCLC with 50% or more PD-L1 expression. It is hypothesized that THIO administration prior to cemiplimab would restore tumor responses to immunotherapy in subjects who either developed resistance or relapsed after receiving first line treatment with an immune check point inhibitor.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; LARGE CELL CARCINOMA; Carcinoma, Non Small Cell Lung; Carcinomas, Non-Small-Cell Lung; Lung Carcinoma, Non-Small-Cell; Lung Carcinomas, Non-Small-Cell; Non-Small-Cell Lung Carcinomas; Non-Small-Cell Lung Carcinoma; Carcinoma, Non-Small Cell Lung; Non-Small Cell Lung Carcinoma; Non-Small Cell Lung Cancer; Nonsmall Cell Lung Cancer

Outcome Measures

Primary Outcomes (5)

• To determine the safety and tolerability of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC

  Part A: Incidence of DLTs

  Up to 2 years

• To assess the efficacy of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC

  ORR, defined as the proportion of subjects with either a CR or PR, as assessed by the investigator based on RECIST v1.1

  Up to 2 years

• To assess the efficacy of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC

  DCR defined as the proportion of subjects with CR, PR, or SD, as assessed by the investigator based on RECIST v1.1

  Up to 2 years

• To determine the safety and tolerability of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC

  Part A: Incidence of DLTs Part A and Part B: Incidence of SAEs overall, by severity, by relationship to THIO and/or cemiplimab, and those that led to discontinuation of THIO and cemiplimab and/or withdrawal from study

  Up to 2 years

• To determine the safety and tolerability of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC

  Part A and Part B: Incidence of TEAEs overall, by severity, by relationship to THIO and/or cemiplimab, and those that led to discontinuation of THIO and cemiplimab and/or withdrawal from study

  Up to 2 years

Secondary Outcomes (11)

• Additional efficacy evaluation

  Up to 2 years

• Safety Parts C and D To determine the safety and tolerability of THIO administered in sequence with cemiplimab in subjects with advanced/metastatic NSCLC

  Up to 2 years

• Additional efficacy evaluation

  Up to 2 years

• Additional efficacy evaluation

  Up to 2 years

• Additional efficacy evaluation

  Up to 2 years

Other Outcomes (11)

• To determine the PK of THIO and assess THIO PK / pharmacodynamics (PDy) exposure-response relationship

  Up to 2 Years

• Investigator-assessed anti-tumor activity of THIO sequenced with cemiplimab based on iRECIST

  Up to 2 Years

• To assess blood biomarkers

  Up to 2 years

Study Arms (4)

Part A

EXPERIMENTAL

Safety lead-in, modified 3+3 design. Part A: Cohort 1: THIO total 360 mg per cycle (120 mg on Days 1-3 Q3W) plus 350 mg cemiplimab on Day 5; Cohort 2 (pending emerging data from Cohort 1): THIO total 180 mg per cycle (60 mg on Days 1-3 Q3W) plus 350 mg cemiplimab on Day 5

Drug: 6-Thio-2'-Deoxyguanosine; Drug: Cemiplimab

Part B

EXPERIMENTAL

Cohort 1: THIO total 60 mg per cycle (20 mg on D1-3 Q3W) plus 350 mg cemiplimab on Day 5; Cohort 2: THIO total 180 mg per cycle (60 mg on D1-3 Q3W) plus 350 mg cemiplimab on Day 5; Cohort 3 (pending emerging data from Part A): THIO total 360 mg per cycle (120 mg on Days 1-3 Q3W) plus 350 mg cemiplimab on Day 5

Drug: 6-Thio-2'-Deoxyguanosine; Drug: Cemiplimab

Part C

EXPERIMENTAL

To obtain clinical evidence of the efficacy and safety of the sequential combination of THIO 180 mg per cycle plus cemiplimab compared to single-agent THIO 180 mg per cycle as third-line treatment in subjects with advanced/metastatic NSCLC.

Drug: 6-Thio-2'-Deoxyguanosine; Drug: Cemiplimab

Part D

EXPERIMENTAL

To determine the efficacy of THIO 180 mg per cycle (60 mg on Days 1-3, sequenced with cemiplimab) when administered as third-line treatment in subjects with advanced/metastatic NSCLC.

Drug: 6-Thio-2'-Deoxyguanosine; Drug: Cemiplimab

Interventions

6-Thio-2'-Deoxyguanosine DRUG

small molecule telomere targeting agent

Also known as: 6-thio-dG, THIO

Part A; Part B; Part C; Part D

Cemiplimab DRUG

programmed cell death protein 1 (PD-1) inhibitor

Also known as: LIBTAYO®

Part A; Part B; Part C; Part D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age at the time of signing the Informed Consent Form (ICF) prior to initiation of any study specific activities/procedures.
• Type of Subject and Disease Characteristics
• Stage 3 or 4 histologically or cytologically confirmed NSCLC which has progressed or relapsed after treatment in the advanced setting
• ○ Stage 4 subjects: Part A and Part B: must have progressed or relapsed after first line treatment. Part C and Part D: must have progressed, discontinued due to toxicity, or relapsed after receiving (only) two prior lines of treatment for NSCLC in the advanced setting.
• ○ Stage 3 subjects - must have already failed, or be ineligible for, local, curative-intent therapy including surgery, and/or chemoradiation. Stage 3 subjects with documented relapse/progression after consolidation therapy with durvalumab following definitive chemoradiotherapy are eligible.
• Subjects must have secondary resistance to the prior ICI, as defined by the Society for Immunotherapy of Cancer (SITC) Immunotherapy Resistance Task Force (IRTF) (Kluger 2020):
• Resistance phenotype Drug exposure requirements Best response Confirmation scan for PD requirement Confirmation scan timeframe Secondary resistance ≥ 6 months CR, PR, SD for \> 6 months Yes \[1\] At least 4 weeks after disease progression (per RECIST V1.1) Other than when tumor growth is very rapid, and subjects are deteriorating clinically.
• Abbreviations: CR=complete response; PD=progressive disease; PR=partial response; SD=stable disease Note: Subjects with drug exposure \> 6 weeks who achieved a PR or CR then progressed before 6 months, would still be eligible.
• Part A and Part B: Only one prior treatment for NSCLC in the advanced setting, which must have included one anti-PD-1/PD-L1 agent with documented radiographic disease progression on or after treatment.
• Prior treatment may have been with anti-PD-1/PD-L1 agent either alone or in combination with a non-anti-PD-1/PD-L1 treatment (e.g., chemotherapy)
• Prior platinum-based chemotherapy is not required for eligibility.
• Subjects receiving more than one ICI in the advanced setting (e.g., anti-PD-1/PD-L1 and anti-CTLA-4 compounds) will not be eligible.
• Part C and Part D: Only two prior treatments for NSCLC in the advanced setting, which must have included an anti-PD-1/PD-L1 agent, a platinum-based chemotherapy, and docetaxel, regardless of order or combination, with documented radiographic disease progression, intolerable toxicity, or relapse after treatment.
• ○ Combination of immune therapy is allowed (e.g., anti-PD-1/PD-L1 and anti-CTLA-4 compounds; anti-PD-1/PD-L1 and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT)-based immunotherapy).
• No prior targeted therapy for driver mutations.

You may not qualify if:

• Have not recovered from adverse events (must be Grade ≤ 1) due to prior anti-cancer treatment.
• Untreated or symptomatic central nervous system (CNS) metastases. Note: subjects with treated asymptomatic brain metastasis are eligible.
• Active gastrointestinal bleeding as evidenced by either hematemesis or melena.
• History of another concurrent malignancy other than the present condition (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 3 years.
• A condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, adrenal replacement doses 10 mg daily prednisone equivalents, and systemic corticosteroids to manage adverse events (AEs) are permitted in the absence of active autoimmune disease.
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy within 2 weeks of screening.
• Positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active hepatitis B or hepatitis C.
• Significant cardiovascular impairment (history of New York Heart Association Functional Classification System Class III or IV) or a history of myocardial infarction or unstable angina within the past 6 months prior to IP initiation.
• a) QTcF \> 480 msec at screening (based on average of triplicate ECGs at baseline).
• i. If the QTc is prolonged in a subject with a pacemaker or bundle branch block, the subject may be enrolled in the study if confirmed by the Medical Monitor.
• Ongoing immune-related/stimulated adverse events (irAEs) from other agents or required permanent discontinuation of prior ICIs due to irAEs. Subjects with resolved irAE may be allowed to enroll following consultation with Sponsor's Medical Monitor (or designee).
• Active autoimmune diseases or history of autoimmune diseases that may relapse, with the following exceptions:
• Controlled type 1 diabetes;
• Hypothyroidism (provided it is managed with hormone replacement therapy only);
• Controlled celiac disease;

Sponsors & Collaborators

• Maia Biotechnology: lead

Study Sites (35)

Central Alabama Research

Birmingham, Alabama, 35209, United States

ACTIVE NOT RECRUITING

Summit Health

Florham Park, New Jersey, 07932, United States

ACTIVE NOT RECRUITING

Sunshine Coast Haematology and Oncology Clinic

Buderim, Queensland, 4556, Australia

SUSPENDED

Cancer Research SA

Adelaide, South Australia, 5000, Australia

SUSPENDED

St. Vincent Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

SUSPENDED

MHAT "HEART AND BRAIN" EAD Clinic of Medical Oncology

Pleven, 5800, Bulgaria

SUSPENDED

MC Synexus Sofia EOOD

Sofia, 1784, Bulgaria

SUSPENDED

MHAT "Serdika" EOOD

Sofia, Bulgaria

SUSPENDED

UMHAT "Sofiamed"

Sofia, Bulgaria

SUSPENDED

Semmelweis Egyetem Pulmonologiai Klinika

Budapest, 25-29, Hungary

NOT YET RECRUITING

Országos Korányi Pulmonológiai Intézet

Budapest, u. 1., Hungary

ACTIVE NOT RECRUITING

Orszagos Onkologiai Intezet

Budapest, u. 7-9, Hungary

ACTIVE NOT RECRUITING

Debreceni Egyetem Klinikai Kozpont, Tudogyogyaszati Klinika

Debrecen, 98, Hungary

ACTIVE NOT RECRUITING

Bács-Kiskun Megyei Oktatókórház, Onkoradiológiai Központ

Kecskemét, 6000, Hungary

ACTIVE NOT RECRUITING

Mátrai Gyógyintézet

Mátraháza, HRSZ7151, Hungary

ACTIVE NOT RECRUITING

Hetenyi Geza Korhaz, Onkologiai Kozpont

Szolnok, u 21, Hungary

ACTIVE NOT RECRUITING

Tüdőgyógyintézet Törökbálint, Onkológiai Osztályc

Törökbálint, 70. 2045, Hungary

ACTIVE NOT RECRUITING

NZOZ FORMED 2 Sp. z o.o.

Oświęcim, Oswiecim, 32-600, Poland

ACTIVE NOT RECRUITING

Centrum Onkologii im. prof. F. Lukaszczyka

Bydgoszcz, 85-796, Poland

ACTIVE NOT RECRUITING

Krakowski Szpital Specjalistyczny im. Jana Pawla II Oddzial Onkologii z Pododdzialem Diagnostyki Nowotworow Klatki Piersiowej

Krakow, 31-202, Poland

ACTIVE NOT RECRUITING

Centrum Terapii Współczesnej J. M. Jasnorzewska

Lodz, 90-338, Poland

ACTIVE NOT RECRUITING

NeuroMed

Lublin, 20-064, Poland

ACTIVE NOT RECRUITING

Med Polonia Sp z o.o.

Poznan, 60-693, Poland

ACTIVE NOT RECRUITING

Centrum Medyczne Mrukmed

Rzeszów, 35-021, Poland

ACTIVE NOT RECRUITING

Centrum Medyczne Pratia

Skorzewo, 60-185, Poland

ACTIVE NOT RECRUITING

Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu, Oddzial Chemioterapii Nowotworow

Torun, 87-100, Poland

ACTIVE NOT RECRUITING

Taipei Veterans General Hospital

Taipei, Beitou District, 11214, Taiwan

RECRUITING

Chang-Gung Memorial Hospital - Linko

Taoyuan, Guishan District, 333, Taiwan

RECRUITING

Tri-Service General Hospital

Taipei, Neihu District, 114, Taiwan

RECRUITING

Chang-Gung Memorial Hospital

Kaohsiung City, Niaosong District, 833, Taiwan

RECRUITING

Taipei Tzu Chi Hospital

New Taipei City, Xindian Dist, 23142, Taiwan

RECRUITING

Taipei Medical University Hospital

Taipei, Xinyi District, 11031, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, Zhongzheng District, Taiwan

RECRUITING

Liv Hospital Ankara, Medikal Onkoloji Bilim Dalı

Ankara, Turkey (Türkiye)

RECRUITING

İstinye Üniversitesi Hastanesi Liv Hospital Bahçeşehir

Istanbul, Turkey (Türkiye)

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Adenocarcinoma; Carcinoma, Large Cell

Interventions

alpha-2'-deoxythioguanosine; cemiplimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Study Officials

• Victor Zaporojan, MD

  Maia Biotechnology

  STUDY CHAIR

Central Study Contacts

Mattew Failor

CONTACT

+1 (312) 416-8592; MFailor@maiabiotech.com

Imy Chiu

CONTACT

ichiu@maiabiotech.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: * Part A (Completed enrolment, N=10): Modified 3+3 design safety lead-in study of THIO 360 mg per cycle (120 mg on Days 1-3, sequenced with cemiplimab). * Part B (Completed enrolment, N=69): Randomized, dose-finding, Simon's 2-stage design, 3-arm study (THIO 60 mg, THIO 180 mg, or THIO 360 mg per cycle; all dose levels sequenced with cemiplimab), with optional extension cohort(s). * Revised Part C (Planned; N-37-48): all enrolled subjects will receive THIO 60 mg administered by 30-minute IV infusions once daily on Days 1-3 of every 3-week cycle (for a total of 180 mg per cycle). In addition, subjects randomized to the sequential combination arm (Arm 1), and subjects enrolled into the Arm 1 Expansion Cohort will also receive a fixed dose of cemiplimab (350 mg IV) on Day 5 of each * Part D (Planned; N=100): Single-arm Efficacy cohort evaluating the efficacy and safety of THIO 180 mg per cycle sequenced with cemiplimab as third-line treatment in patients with advanced/metastatic NSCLC.

Study Record Dates

• First Submitted: December 5, 2021
• First Posted: January 26, 2022
• Study Start: June 8, 2022
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

HU (8); TU (2); TW (7); AU (3); US (2); PL (9); BU (4)