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Trial record 1 of 1 for:    THIO 101
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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 : July 8, 2022
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: 6-Thio-2'-Deoxyguanosine Drug: Cemiplimab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 182 participants
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
Official Title: 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)
Actual Study Start Date : June 8, 2022
Estimated Primary Completion Date : June 3, 2024
Estimated Study Completion Date : December 2, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part A

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
small molecule telomere targeting agent
Other Names:
  • 6-thio-dG
  • THIO

Drug: Cemiplimab
programmed cell death protein 1 (PD-1) inhibitor
Other Name: LIBTAYO®

Experimental: Part B
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
small molecule telomere targeting agent
Other Names:
  • 6-thio-dG
  • THIO

Drug: Cemiplimab
programmed cell death protein 1 (PD-1) inhibitor
Other Name: LIBTAYO®

Experimental: Optional Part C
THIO total 540 mg per cycle (180 mg on D1-3 Q3W) plus 350 mg cemiplimab on Day 5
Drug: 6-Thio-2'-Deoxyguanosine
small molecule telomere targeting agent
Other Names:
  • 6-thio-dG
  • THIO

Drug: Cemiplimab
programmed cell death protein 1 (PD-1) inhibitor
Other Name: LIBTAYO®




Primary Outcome Measures :
  1. To determine the incidence of dose limiting toxicities (DLTs) [Safety and Tolerability] of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC [ Time Frame: Up to 1 year ]
    Incidence of dose limiting toxicities (DLTs; applicable for Part A and Part C) overall, by severity, by relationship to THIO, and those that led to discontinuation of THIO and/or withdrawal from study.

  2. To determine the incidence of treatment-emergent adverse events (TEAEs) [Safety and Tolerability] of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC [ Time Frame: Up to 1 year ]
    Incidence of treatment-emergent adverse events (TEAEs) overall, by severity, by relationship to THIO, and those that led to discontinuation of THIO and/or withdrawal from study.

  3. To determine the incidence of serious adverse events (SAEs) [Safety and Tolerability] of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC [ Time Frame: Up to 1 year ]
    Incidence of serious adverse events (SAEs) overall, by severity, by relationship to THIO, and those that led to discontinuation of THIO and/or withdrawal from study.

  4. To assess the efficacy of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC by observing the Overall Response Rate (ORR) in telomerase-positive subjucts. [ Time Frame: Up to 1 year ]
    Overall Response Rate (ORR) defined as the proportion of subjects with best overall confirmed response of either a complete response (CR) or partial response (PR) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

  5. To assess the efficacy of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC by observing the Disease Control Rate (DCR) in telomerase-positive subjects. [ Time Frame: Up to 1 year ]
    Disease Control Rate (DCR) defined as a complete response (CR), partial response (PR), or stable disease (SD) as assessed by the investigator based on RECIST v1.1 criteria.


Secondary Outcome Measures :
  1. Additional efficacy measurement by observing Duration of Response (DoR) in subjects. [ Time Frame: Up to 1 year ]
    Duration of Response (DoR) in telomerase-positive subjects assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

  2. Efficacy measured by observing Progression-Free Survival (PFS) in subjects. [ Time Frame: Up to 1 year ]
    Progression-Free Survival (PFS) in telomerase-positive subjects assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

  3. Measure efficacy by observing Overall Survival (OS) in subjects. [ Time Frame: Up to 1 year ]
    Overall Survival (OS) in telomerase-positive subjects assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.


Other Outcome Measures:
  1. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To be eligible for participation in this study, subjects must meet all the following:

  1. 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.
  2. Stage 3 or Stage 4 NSCLC who either progressed or relapsed after ICI, as defined by the Society for Immunotherapy of Cancer (SITC) immunotherapy resistance task force.

    Subjects with drug exposure >6 weeks but not meeting the criteria for either primary or secondary resistance, can also be included (e.g., have achieved initially a PR, then progressed before 6 months).

    Subjects who received neoadjuvant or adjuvant therapies with ICIs for the initial cancer diagnosis may also be eligible, following consultation with Sponsor's Medical Monitor (or designee). Prior treatment with PD-1/PD-L1 ICIs therapy alone or in combination with a platinum-based chemotherapy (i.e., platinum-based chemotherapy followed by ICI therapy) will be allowed. ICI treatment may have been part of 1st or 2nd line, but not both.

  3. Must have histologically or cytologically confirmed NSCLC.
  4. At least one measurable target lesion that meets the definition of RECIST v1.1.
  5. Willing to provide archived tumor tissue samples either formalin fixed paraffin embedded (FFPE) block OR at least 10 unstained slides.
  6. Life expectancy of greater than 12 weeks.
  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  8. Demonstrate adequate organ function as defined below. All screening laboratories should be performed within 14 days of initiating IP:

    • Bone marrow function: neutrophil count ≥ 1500/mm3, hemoglobin ≥ 9.0 g/dL, platelet count ≥ 100,000/mm3;
    • Liver function: total bilirubin ≤ 1.5 x the upper limit of normal (ULN) based on the standard value of each institution, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN;
    • Renal function: serum creatinine ≤ 1.5 x ULN based on the reference laboratory.
  9. Women of childbearing potential (WOCBP) must have negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to receiving the first administration of IP.

    Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

  10. WOCBP must agree to use a highly effective birth control and refrain from oocyte donation during the study (prior to the first dose with THIO, for the duration of the treatment with THIO plus 6 months after last dose of IP), if conception is possible during this interval.
  11. Male subjects and WOCBP partners of male subjects should use a combination of a male condom from first dose of THIO (Cycle 1, Day 1), for the duration of the treatment with THIO plus 6 months after last dose of IP, unless permanently sterile by bilateral orchidectomy. Male subjects should also refrain from sperm donation during this time.
  12. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion Criteria:

  1. Have not recovered from adverse events (must be Grade ≤1) due to agents administered more than 4 weeks earlier.
  2. Untreated or symptomatic central nervous system (CNS) metastases. Note: subjects with treated asymptomatic brain metastasis are eligible.
  3. Active gastrointestinal bleeding as evidenced by either hematemesis or melena.
  4. 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.
  5. 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.
  6. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy within 2 weeks of screening.
  7. Positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active hepatitis B or hepatitis C.
  8. Positive for COVID-19 using polymerase chain reaction (PCR) test; subjects with positive PCR test will be eligible after 2 consecutive negative results are obtained, minimum 1 week apart.
  9. 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.
  10. Ongoing immune-related/stimulated adverse events (irAEs) from other agents or required permanent discontinuation of prior ICIs due to immune-related AEs (irAEs). Subjects with resolved irAE may be allowed to enroll following consultation with Sponsor's Medical Monitor (or designee).
  11. 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;
    • Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or alopecia);
    • Any other disease that is not expected to recur in the absence of external triggering factors.
  12. Pregnancy or lactating.
  13. A serious nonmalignant disease (eg, psychiatric, substance abuse, uncontrolled intercurrent illness, etc.) that could compromise protocol objectives in the opinion of the investigator and/or the Sponsor.
  14. Any other condition that, in the opinion of the investigator, would prohibit the subject from participating in the study.
  15. Prior chemotherapy, targeted therapy, and immunotherapy within the 28 days prior to Screening.
  16. Undergone major surgery within 4 weeks prior to Cycle 1, Day 1.
  17. Received blood, red blood cell or platelet transfusion within 2 weeks before the first dose of IP.
  18. Any vaccines (live, attenuated, inactivated or research vaccines) within 30 days prior to the first dose of IP. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed.
  19. Prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
  20. Actively participating in another clinical study.

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05208944


Contacts
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Contact: Stuart Byham (919) 271-6528 sbyham@maiabiotech.com
Contact: Paul Watkins (805) 231-5740 pwatkins@maiabiotech.com

Locations
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Australia, Queensland
Sunshine Coast Haematology and Oncology Clinic Active, not recruiting
Buderim, Queensland, Australia, 4556
Australia, South Australia
Cancer Research SA Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Rohit Joshi, MD    08 8359 2565    rjoshi@cancerresearchsa.com.au   
Contact: Meena Okera, MD    08 8359 2565    mokera@cancerresearchsa.com.au   
Principal Investigator: Rohit Joshi, MD         
Sponsors and Collaborators
Maia Biotechnology
Investigators
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Study Chair: Mihail Obrocea, MD Maia Biotechnology
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Responsible Party: Maia Biotechnology
ClinicalTrials.gov Identifier: NCT05208944    
Other Study ID Numbers: THIO-101
First Posted: January 26, 2022    Key Record Dates
Last Update Posted: July 8, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Maia Biotechnology:
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
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Cemiplimab
Antineoplastic Agents, Immunological
Antineoplastic Agents