A Phase III Study With THIO + Cemiplimab vs Chemotherapy as 3rd Line Treatment in Advanced/Metastatic NSCLC

NCT06908304 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: THIO-1042024-520164-33-00
• Study Type: interventional
• Target: 300
• Locations: 4 countries
• Sites: 15

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; Non-Small Cell Lung Carcinoma; Non-Small Cell Lung Cancer; Large Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival as defined as the time from randomization to death from any cause.

  Within 2 Years

Secondary Outcomes (5)

• Objective Radiographic Response

  Within 2 Years

• Disease Control Rate

  Within 2 Years

• Duration of Response

  Within 2 Years

• Progressive Free Survival

  Within 2 Years

• Treatment Emergent Adverse events and Serious Adverse Events

  Within 2 Years

Other Outcomes (5)

• Exploratory Objectives

  Within 2 Years

• Exploratory Objectives

  Within 2 Years

• Exploratory Objectives

  Within 2 Years

Study Arms (2)

THIO + Cemiplimab Arm

EXPERIMENTAL

THIO 60mg, 30-min IV infusions, Days 1-3 (180 mg/Cycle) Cemplimab 350 mg, 30-min IV infusion, Day 5 3-Week Cycle

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

Investigator's choice of single-agent chemotherapy (vinorelbine, gemcitabine, or docetaxel)

ACTIVE COMPARATOR

Chemotherapy Agent \[1\] Dosing Regimen No. of Subjects (Planned) Option 1: Vinorelbine 30 mg/m2 IV on D1, D8, and D15 Q3W \~150 \[3\] Option 2: Gemcitabine 1250 mg/m2 IV on D1 and D8 Q3W Option 3: Docetaxel 75 mg/m2 IV on D1 Q3W \[2\] Abbreviations: D = day (within a 21-day cycle); IV= intravenous; Q3W=every 3 weeks (21-day cycles) 1. Standard of Care (for example vinorelbine, gemcitabine, or docetaxel chemotherapy, if not previously exposed, per Investigator's Choice) 2. Docetaxel 60-65 mg/m2 permitted based on country-specific approvals. 3. Within the control arm, there are no limits on the number of subjects who can be treated with any of the chemotherapy agents.

Drug: Docetaxel; Drug: Vinorelbine; Drug: Gemcitabine alone

Interventions

6-Thio-2'-Deoxyguanosine DRUG

small molecule telomere targeting agent

Also known as: 6-thio-dG, THIO, ateganosine

THIO + Cemiplimab Arm

Cemiplimab DRUG

programmed cell death protein 1 (PD-1) inhibitor

Also known as: LIBTAYO®

THIO + Cemiplimab Arm

Docetaxel DRUG

Chemotherapy drug; inhibits cell division by stabilizing microtubules. Used for breast, lung, and prostate cancers.

Also known as: Taxotere, Docecad

Investigator's choice of single-agent chemotherapy (vinorelbine, gemcitabine, or docetaxel)

Vinorelbine DRUG

Chemotherapy drug; disrupts microtubule formation, inhibiting cell division. Used for non-small cell lung cancer and breast cancer.

Also known as: Navelbine, Vinorelbine tartrate

Investigator's choice of single-agent chemotherapy (vinorelbine, gemcitabine, or docetaxel)

Gemcitabine alone DRUG

Chemotherapy drug; inhibits DNA synthesis. Used for pancreatic, lung, breast, and ovarian cancers.

Also known as: Gemzar

Investigator's choice of single-agent chemotherapy (vinorelbine, gemcitabine, or docetaxel)

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.
• Disease Characteristics
• Stage 3b or 4 histologically or cytologically confirmed NSCLC. Note: Stage is determined at the time of diagnosis.
• Two (2) prior lines of systemic treatment for advanced/metastatic disease, including an ICI (anti-PD-1/PD-L1) and a platinum-based chemotherapy (given in combination or in separate lines) for advanced/metastatic disease.
• Note: The combination of primary therapy followed by maintenance is considered as one line of therapy. Prior treatment with docetaxel is preferred (but not mandated) and is a pre-specified stratification factor.
• Documented progression or intolerance following the most recent line of therapy.
• Stage 4 subjects - must have progressed or relapsed after first-line treatment.
• Stage 3b subjects - must have already failed, or be ineligible for, local, curative-intent therapy including surgery, and/or chemoradiation.
• Note: Local, curative-intent therapy including surgery, and/or chemoradiation is not considered a treatment line in the advanced setting.
• Documented secondary resistance to the prior ICI treatment, as defined by the SITC 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) \[1\] 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
• No prior targeted therapy for driver mutations.
• At least one measurable target lesion that meets the definition of RECIST v1.1, with documented progression following the most recent line of therapy.
• An archival tissue sample (formalin fixed paraffin-embedded \[FFPE\] tissue block or unstained slides) is required if tissue is available at baseline.

You may not qualify if:

• For subjects who have received prior treatment with a checkpoint inhibitor: primary resistance to prior checkpoint inhibitor, as defined by the SITC IRTF (Kluger, 2020):
• Resistance phenotype Drug exposure requirements Best response Confirmation scan for PD requirement Confirmation scan timeframe Primary resistance ≥ 6 weeks PD; SD for \< 6 months Yes \[1\] At least 4 weeks after initial disease progression (per RECIST v1.1) \[1\] 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 partial or complete response then progressed before six months, would still be eligible.
• Untreated or symptomatic central nervous system (CNS) metastases. Note: Subjects with treated asymptomatic brain metastasis are eligible.
• Prior chemotherapy and/or non-biologic targeted therapy within 28 days, or biologic targeted therapy, immunotherapy, and/or radiation therapy within 42 days prior to start of study treatment.
• Note: Subjects who receive targeted radiation therapy for localized palliative care may be eligible to start study treatment earlier than 42 days with Medical Monitor agreement.
• Prior treatment with cemiplimab.
• Prior treatment with a targeted therapy for an epidermal growth factor receptor (EGFR) mutation.
• Received blood, red blood cell or platelet transfusion within 14 days prior to start of study treatment.
• Any live, attenuated, inactivated or research vaccines within 30 days prior to start of study treatment.
• Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed.
• Prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
• Undergone major surgery within 28 days prior to start of study treatment. Medical conditions
• Have not recovered to Grade ≤ 1 from adverse events due to prior anti-cancer treatment.
• Ongoing immune-related / stimulated adverse events (irAEs) from other agents or required permanent discontinuation of prior ICIs due to irAEs.

Sponsors & Collaborators

• Maia Biotechnology: lead

Study Sites (15)

Centrum Medyczne Pratia

Poznan, Poland

RECRUITING

Oncolab S.R.L.

Craiova, Romania

RECRUITING

Spitalul Clinic Municipal de Urgenta Timisoara/ Clinica de Oncologie Medicala

Timișoara, Romania

RECRUITING

Changhua Christian Hospital (CCH)

Changhua, Taiwan

RECRUITING

Taipei Tzu Chi Hospital

Chiayi City, Taiwan

RECRUITING

Chang-Gung Memorial Hospital - KaoHsiung

Kaohsiung City, Taiwan

RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)

Kaohsiung City, Taiwan

RECRUITING

Chung Shan Medical University Hospital (CSMUH)

Taichung, Taiwan

RECRUITING

Taipei Medical University Hospital (TMUH)

Taipei, Taiwan

RECRUITING

Tri-Service General Hospital

Taipei, Taiwan

RECRUITING

Chang-Gung Memorial Hospital - Linko

Taoyuan, Taiwan

RECRUITING

Medicalpark Hastanesi

Adana, Turkey (Türkiye)

RECRUITING

Liv Hospital

Ankara, Turkey (Türkiye)

RECRUITING

Göztepe Süleyman Yalçın Şehir Hastanesi

Istanbul, Turkey (Türkiye)

RECRUITING

İstinye University

Istanbul, Turkey (Türkiye)

RECRUITING

MeSH Terms

Conditions

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

Interventions

alpha-2'-deoxythioguanosine; cemiplimab; Docetaxel; Vinorelbine; Gemcitabine

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Victor Zaporojan, Medical Doctor

  MAIA Biotechnology Senior Medical Director

  STUDY DIRECTOR

Central Study Contacts

Matthew Failor

CONTACT

704-936-8435; mfailor@maiabiotech.com

Imy Chiu

CONTACT

ichiu@maiabiotech.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2025
• First Posted: April 3, 2025
• Study Start: December 8, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1); TU (4); RO (2); TW (8)