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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05208944




Registration number
NCT05208944
Ethics application status
Date submitted
5/12/2021
Date registered
26/01/2022

Titles & IDs
Public title
THIO Sequenced With Cemiplimab in Advanced NSCLC
Scientific 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)
Secondary ID [1] 0 0
2021-005136-34
Secondary ID [2] 0 0
THIO-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non-Small-Cell Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 6-Thio-2'-Deoxyguanosine
Treatment: Drugs - Cemiplimab

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

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

Experimental: Optional Part C - THIO total 540 mg per cycle (180 mg on D1-3 Q3W) plus 350 mg cemiplimab on Day 5


Treatment: Drugs: 6-Thio-2'-Deoxyguanosine
small molecule telomere targeting agent

Treatment: Drugs: Cemiplimab
programmed cell death protein 1 (PD-1) inhibitor
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To determine the incidence of dose limiting toxicities (DLTs) [Safety and Tolerability] of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC
Timepoint [1] 0 0
Up to 1 year
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
Up to 1 year
Primary outcome [3] 0 0
To determine the incidence of serious adverse events (SAEs) [Safety and Tolerability] of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC
Timepoint [3] 0 0
Up to 1 year
Primary outcome [4] 0 0
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.
Timepoint [4] 0 0
Up to 1 year
Primary outcome [5] 0 0
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.
Timepoint [5] 0 0
Up to 1 year
Secondary outcome [1] 0 0
Additional efficacy measurement by observing Duration of Response (DoR) in subjects.
Timepoint [1] 0 0
Up to 1 year
Secondary outcome [2] 0 0
Efficacy measured by observing Progression-Free Survival (PFS) in subjects.
Timepoint [2] 0 0
Up to 1 year
Secondary outcome [3] 0 0
Measure efficacy by observing Overall Survival (OS) in subjects.
Timepoint [3] 0 0
Up to 1 year

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/06/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
2/12/2024
Actual
Sample size
Target
182
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Sunshine Coast Haematology and Oncology Clinic - Buderim
Recruitment hospital [2] 0 0
Cancer Research SA - Adelaide
Recruitment hospital [3] 0 0
St. Vincent Hospital Melbourne - Fitzroy
Recruitment postcode(s) [1] 0 0
4556 - Buderim
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
Bulgaria
State/province [1] 0 0
Pleven
Country [2] 0 0
Bulgaria
State/province [2] 0 0
Sofia
Country [3] 0 0
Hungary
State/province [3] 0 0
Budapest
Country [4] 0 0
Hungary
State/province [4] 0 0
Debrecen
Country [5] 0 0
Hungary
State/province [5] 0 0
Kecskemet
Country [6] 0 0
Hungary
State/province [6] 0 0
Matrahaza
Country [7] 0 0
Hungary
State/province [7] 0 0
Szolnok
Country [8] 0 0
Hungary
State/province [8] 0 0
Törökbálint
Country [9] 0 0
Poland
State/province [9] 0 0
Oswiecim
Country [10] 0 0
Poland
State/province [10] 0 0
Bydgoszcz
Country [11] 0 0
Poland
State/province [11] 0 0
Krakow
Country [12] 0 0
Poland
State/province [12] 0 0
Lodz
Country [13] 0 0
Poland
State/province [13] 0 0
Lublin
Country [14] 0 0
Poland
State/province [14] 0 0
Poznan
Country [15] 0 0
Poland
State/province [15] 0 0
Rzeszow,
Country [16] 0 0
Poland
State/province [16] 0 0
Skorzewo
Country [17] 0 0
Poland
State/province [17] 0 0
Torun

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Maia Biotechnology
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Mihail Obrocea, MD
Address 0 0
Maia Biotechnology
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Paul Watkins
Address 0 0
Country 0 0
Phone 0 0
805-231-5740
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05208944