THIO Sequenced with Cemiplimab in Advanced NSCLC
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Drug: 6-Thio-2'-Deoxyguanosine
- Registration Number
- NCT05208944
- Lead Sponsor
- Maia Biotechnology
- 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.
- Detailed Description
The THIO-101 study evaluates the safety and efficacy of different doses of THIO sequenced with fixed dose of cemiplimab (referred to as investigational products \[IP\]) in subjects with advanced NSCLC who progressed, discontinued due to toxicity, or relapsed after receiving prior therapy with an anti-PD-1/PD-L1 agent.
This study is a Phase 2, open-label, multicenter study comprised of 4 parts:
* 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 to 48)
* 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.
This study aims to establish THIO followed by cemiplimab as a potential treatment regimen in a high unmet medical need setting.
A Safety Review Committee (SRC) will monitor subject safety during the study and will make recommendations to the Sponsor regarding enrollment, eg, de-escalating dose in Part A, proceeding to Part B, expanding an arm in Part B, opening Part C, and Part D of the study based on emerging data from prior study parts.
In each study part, on Cycle 1, Day 1, eligible subjects initiate treatment with THIO (at doses described for each study part below) as intravenous (IV) infusion, once daily, on Days 1-3 of every 3-week cycle (Q3W) followed by a fixed dose of cemiplimab (350 mg IV) on Day 5 Q3W. The only exception is the randomized Arm 2 of Part C, where subjects will be receiving single agent THIO (without sequential cemiplimab). Study treatment may continue until PD, occurrence of an unacceptable toxicity, withdrawal of consent, death, or two years on treatment, whichever occurs first.
The initial radiographic imaging for baseline assessment is to be conducted by the investigator up to 28 days before the first dose of THIO for tumor evaluation and measurements. The on-treatment radiographic assessments are to be performed every 2 cycles (every 6 weeks, ± 7 days) during the first year of treatment, and then every 3 cycles (every 9 weeks, ± 14 days) during the second year of treatment until documented PD, initiation of a new anti-cancer treatment, or completion of follow-up, whichever occurs first. The radiographic scans are to be assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and/or iRECIST until PD, initiation of a new anti-cancer treatment, or end of the study, whichever occurs first. In Part D of the study, radiographic scans will also be assessed by a blinded independent central review (BICR) committee. Confirmation of CR and PR per RECIST v1.1 by consecutive radiographic imaging (computed tomography \[CT\]/magnetic resonance imaging \[MRI\]; same modality to be used for a given subject throughout the study) assessment 4-8 weeks from the date of first documentation is required. In Parts A, B, and C, radiographic scans are/will be collected and held for possible future retrospective independent evaluation.
To account for tumor pseudoprogression or delayed response with anti-PD1/PD-L1 immunotherapies, subjects may continue to receive IP beyond RECIST v1.1 defined progression at the discretion of the investigator and be assessed at a subsequent tumor assessment time point (≥ 4 weeks after the date of initial documentation of disease progression) to confirm PD according to iRECIST. Subjects must be consented to receive the IP beyond the initial progression and will discontinue IP once the progression is confirmed by iRECIST.
Safety assessments for all study patients (Parts A, B, C, and D) during each treatment cycle include complete or abbreviated physical examinations, routine safety laboratory testing (hematology, clinical chemistry, coagulation), thyroid hormone testing, vital sign evaluations, and electrocardiograms (ECGs).
All subjects will undergo end of treatment (EoT) visit 30 days post last treatment with IP. Subjects will be followed every 3 months until death, withdrawal of consent, loss to follow-up, or study termination by the Sponsor, whichever occurs first. Long-term follow-up can be via clinic visit, phone call to the subject or referring physician, or other method deemed appropriate by the site and should assess survival, progression, subsequent anti-cancer therapy and response. Any subject who discontinues treatment for reasons other than disease progression will continue to have radiographic assessments per standard of care and no less than every 3 months for the first year, and then every 6 months until documented disease progression, initiation of a new anti-cancer treatment, or end of follow-up. Subjects in Parts A and B only who discontinued treatment due to disease progression per RECIST 1.1 and did not receive post-progression treatment could be asked to complete standard of care radiographic assessments every 3 months for up to 1 year and then every 6 months until initiation of a new anti-cancer treatment or completion of follow-up. Response assessment in follow-up will include at minimum the modality used to determine response.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 227
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A 6-Thio-2'-Deoxyguanosine 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 Part A Cemiplimab 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 Part B 6-Thio-2'-Deoxyguanosine 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 Part B Cemiplimab 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 Part C 6-Thio-2'-Deoxyguanosine 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. Part C Cemiplimab 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. Part D 6-Thio-2'-Deoxyguanosine 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. Part D Cemiplimab 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.
- Primary Outcome Measures
Name Time Method To determine the safety and tolerability of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC Up to 2 years 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
To assess the efficacy of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC Up to 2 years DCR defined as the proportion of subjects with CR, PR, or SD, as assessed by the investigator based on RECIST v1.1
- Secondary Outcome Measures
Name Time Method Additional efficacy evaluation Up to 2 years Part D: Objective Radiographic Response Rate (ORR) defined as the proportion of subjects with a confirmed CR or PR, as assessed by BICR based on RECIST v1.1.
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 Incidence of and fatal TEAEs.
Trial Locations
- Locations (27)
Chang-Gung Memorial Hospital - Linko
🇨🇳Taoyuan City, Guishan District, Taiwan
Liv Hospital Ankara, Medikal Onkoloji Bilim Dalı
🇹🇷Ankara, Turkey
İstinye Üniversitesi Hastanesi Liv Hospital Bahçeşehir
🇹🇷Istanbul, Turkey
Sunshine Coast Haematology and Oncology Clinic
🇦🇺Buderim, Queensland, Australia
Cancer Research SA
🇦🇺Adelaide, South Australia, Australia
St. Vincent Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
MHAT "HEART AND BRAIN" EAD Clinic of Medical Oncology
🇧🇬Pleven, Bulgaria
MC Synexus Sofia EOOD
🇧🇬Sofia, Bulgaria
MHAT "Serdika" EOOD
🇧🇬Sofia, Bulgaria
UMHAT "Sofiamed"
🇧🇬Sofia, Bulgaria
Semmelweis Egyetem Pulmonologiai Klinika
🇭🇺Budapest, Hungary
Országos Korányi Pulmonológiai Intézet
🇭🇺Budapest, Hungary
Orszagos Onkologiai Intezet
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont, Tudogyogyaszati Klinika
🇭🇺Debrecen, Hungary
Bács-Kiskun Megyei Oktatókórház, Onkoradiológiai Központ
🇭🇺Kecskemet, Hungary
Mátrai Gyógyintézet
🇭🇺Matrahaza, Hungary
Hetenyi Geza Korhaz, Onkologiai Kozpont
🇭🇺Szolnok, Hungary
Tüdőgyógyintézet Törökbálint, Onkológiai Osztályc
🇭🇺Törökbálint, Hungary
NZOZ FORMED 2 Sp. z o.o.
🇵🇱Oswiecim,, Oswiecim, Poland
Centrum Onkologii im. prof. F. Lukaszczyka
🇵🇱Bydgoszcz, Poland
Krakowski Szpital Specjalistyczny im. Jana Pawla II Oddzial Onkologii z Pododdzialem Diagnostyki Nowotworow Klatki Piersiowej
🇵🇱Krakow, Poland
Centrum Terapii Współczesnej J. M. Jasnorzewska
🇵🇱Lodz, Poland
NeuroMed
🇵🇱Lublin, Poland
Med Polonia Sp z o.o.
🇵🇱Poznań, Poland
Centrum Medyczne Mrukmed
🇵🇱Rzeszow,, Poland
Centrum Medyczne Pratia
🇵🇱Skorzewo, Poland
Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu, Oddzial Chemioterapii Nowotworow
🇵🇱Torun, Poland