THIO Sequenced With Cemiplimab in Advanced NSCLC
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ClinicalTrials.gov Identifier: NCT05208944 |
Recruitment Status :
Recruiting
First Posted : January 26, 2022
Last Update Posted : August 31, 2023
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Tracking Information | |||||||||
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First Submitted Date ICMJE | December 5, 2021 | ||||||||
First Posted Date ICMJE | January 26, 2022 | ||||||||
Last Update Posted Date | August 31, 2023 | ||||||||
Actual Study Start Date ICMJE | June 8, 2022 | ||||||||
Estimated Primary Completion Date | June 3, 2024 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
Determine Safety and tolerability of THIO administered in sequence with cemiplimab [ Time Frame: Up to 1 year ] Number of patients with DLT as defined in the protocol
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Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Not Provided | ||||||||
Current Other Pre-specified Outcome Measures |
Exploratory Biomarkers [ Time Frame: Up to 1 year ] On-target activity of THIO assessed in circulating tumor cells (CTCs, by Telomere Dysfunction-Induced Foci (TIFs) assay; genomic DNA damage determined in CTCs by gamma-H2AX induction assay
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Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | THIO Sequenced With Cemiplimab in Advanced NSCLC | ||||||||
Official Title ICMJE | A Multicenter, Open-Label, Dose-Finding, Phase 2 Study Evaluating THIO Sequenced With Cemiplimab (LIBTAYO®) in Subjects With Advanced Non-Small Cell Lung Cancer (NSCLC) | ||||||||
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. |
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Detailed Description | The current Phase 2, open-label, multicenter study, comprised of 3 parts, is designed to evaluate the safety and efficacy of THIO sequenced with cemiplimab in subjects with advanced NSCLC. This study could establish THIO followed by cemiplimab as a potential treatment regimen in a high unmet medical need setting. The study evaluates the safety and efficacy of different doses of THIO sequenced with fixed-dose of cemiplimab (collectively called investigational product [IP]) in subjects with advanced NSCLC who progressed or relapsed after receiving first line therapy which included ICI. This study will be a Phase 2, open-label, multicenter study comprised of 3 parts:
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 and opening Part C (optional) of the study based on emerging data from prior study parts. In each study part, on Cycle 1, Day 1, eligible subjects will initiate treatment with THIO (doses will be as described for each study part below) as intravenous (IV) infusion on Days 1-3 of every 3 week cycle (Q3W) followed by a fixed-dose of cemiplimab (350 mg IV) on Day 5 Q3W. Subjects may continue dosing with THIO followed by cemiplimab Q3W until disease progression or occurrence of an unacceptable toxicity, withdrawal of consent, death, or one year on treatment. The initial radiographic imaging for baseline assessment will be conducted by the investigator within 28 days of the first dose of THIO (if not performed in the 4-6 weeks prior to screening) for tumor evaluation and measurements. The on-treatment radiographic assessments will be performed initially at 6 weeks intervals (ie. Cycle 3, Day 1 and Cycle 5, Day 1) and repeated thereafter every 9-12 weeks ± 7 days as clinically indicated. The radiographic scans will be assessed by the investigator according to RECIST v1.1 and/or immune RECIST (iRECIST) until disease progression, or until initiation of a new anticancer treatment (whichever occurs first). Confirmation of CR, PR, stable disease (SD),and PD by a consecutive radiographic imaging (computed tomography/magnetic resonance imaging; same modality to be used for a given subject throughout the study) assessment at least 4 weeks from the date of first documentation will be required. Radiographic scans will be collected and held for possible future retrospective independent evaluation. To account for tumor pseudoprogression or delayed response with anti-PD-1/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 later but not exceeding 6 to 8 weeks from the date of initial documentation of disease progression) to confirm disease progression according to iRECIST. Subjects must be consented to receive the IP beyond the initial progression and will discontinue IP once the progression is confirmed. All subjects will undergo end of treatment (EoT) visit 30 days post last treatment with IP. Subjects will have follow-up visits every 6 weeks for approximately 6 months and then at 9 months and 12 months after the last dose of IP or until they start a new anticancer therapy, whichever is earlier. In subjects who discontinued IP due to toxicity, radiographic imaging will be done every 3 months until disease progression or until the subject initiates another anti-cancer therapy. In each study part, for each subject, the study is expected to last as follows: Screening period: Up to 28 days Treatment period: Until disease progression assessed by the Investigator per RECIST v1.1 and/or iRECIST or occurrence of an unacceptable toxicity, withdrawal of consent, unacceptable toxicity, disease progression, death, or one year on treatment Short-term Follow- up: Up to 30 days after the last dose of THIO Long-term Follow-up: Up to a maximum of 12 months after the last dose of IP of the last subject or earlier if the study is terminated by the Sponsor The Safety Review Committee (SRC) will be comprised of Sponsor's Medical Monitor (or designee), safety physician, statistician and a subset of investigators. The SRC will meet regularly to review the safety information of each study part and make recommendation to the Sponsor. The Sponsor has carefully considered potential risks, uncertainties, and antitumor benefits that may be associated with THIO + cemiplimab for the treatment of advanced NSCLC. The potential risks have been taken into consideration in the design and safety monitoring of this study to mitigate any risk. The study safety measures comprise of specific inclusion/exclusion criteria for participation in the study. This study also includes the medical management of potential toxicities as well as guidance on investigational product (IP) dosing, interruption or discontinuation. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Sequential Assignment Intervention Model Description: Part A will utilize a modified 3+3 design whereby up to 2 safety lead-in cohorts of 6 subjects each, will be sequentially assigned to receive THIO and cemiplimab. Masking: None (Open Label)Primary Purpose: Treatment |
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Condition ICMJE | Carcinoma, Non-Small-Cell Lung | ||||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
182 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | December 2, 2024 | ||||||||
Estimated Primary Completion Date | June 3, 2024 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE | Inclusion Criteria: To be eligible for participation in this study, subjects must meet all the following:
Exclusion Criteria:
20. Currently enrolled in a clinical study involving another IP or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. 21. Participated, within the last 30 days, in a clinical study involving an IP (other than the IP used in this study), unless a minimum of 30 days or 5 half-lives (whichever is longer) have passed before enrollment in the present clinical study. 22. History of allergy to excipients of THIO or cemiplimab. |
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Australia, Bulgaria, Hungary, Poland | ||||||||
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Administrative Information | |||||||||
NCT Number ICMJE | NCT05208944 | ||||||||
Other Study ID Numbers ICMJE | THIO-101 2021-005136-34 ( EudraCT Number ) |
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Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Maia Biotechnology | ||||||||
Original Responsible Party | Same as current | ||||||||
Current Study Sponsor ICMJE | Maia Biotechnology | ||||||||
Original Study Sponsor ICMJE | Same as current | ||||||||
Collaborators ICMJE | Not Provided | ||||||||
Investigators ICMJE |
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PRS Account | Maia Biotechnology | ||||||||
Verification Date | August 2023 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |