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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 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 assess the efficacy 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 assess the efficacy of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC
Timepoint [3] 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
Inclusion Criteria

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

Age

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.

Type of Subject and Disease Characteristics
2. Stage 3 or 4 histologically or cytologically confirmed NSCLC which has progressed or relapsed after treatment in the advanced setting ? Stage 4 subjects - must have progressed or relapsed after first line treatment.

* Stage 3 subjects - must have already failed, or be ineligible for, local, curative-intent therapy including surgery, and/or chemoradiation. Stage 3 subjects with documented relapse/progression after consolidation therapy with durvalumab following definitive chemoradiotherapy are eligible.
* Patients with primary resistance, as defined by the Society for Immunotherapy of Cancer (SITC) immunotherapy resistance task force (Kluger, 2020), are excluded:

Resistance phenotype Drug exposure requirements Best response Confirmation scan for PD requirement Confirmation scan timeframe Primary resistance

* 6 weeks PD; SD for < 6 months Yes1 At least 4 weeks after initial disease progression (per RECIST V1.1) Secondary resistance
* 6 months CR, PR, SD for > 6 months Yes1 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.

* Subjects with drug exposure > 6 weeks who achieved a PR or CR then progressed before 6 months, would still be eligible.

3. Only one prior treatment for NSCLC in the advanced setting, which must have included one anti-PD-1/PD-L1 agent with documented radiographic disease progression on or after treatment.
* Prior treatment may have been with anti-PD-1/PD-L1 agent either alone or in combination with a non-anti-PD-1/PD-L1 treatment (e.g., chemotherapy)
* Prior platinum-based chemotherapy is not required for eligibility.
* Subjects receiving more than one ICI in the advanced setting (e.g., anti-PD-1/PD-L1 and anti-CTLA-4 compounds) will not be eligible.

4. At least one measurable target lesion that meets the definition of RECIST v1.1.

5. An archival tissue sample (FFPE tissue block or unstained slides) is required if tissue is available at baseline. Sample does not need to be received by central lab prior to C1D1. Subjects without archival tissue available at baseline may be eligible with Medical Monitor approval.

Diagnostic Assessments 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 7. Demonstrate adequate organ function as defined below. All screening laboratories should be performed up to 14 days before 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), up to = 3 × ULN due to Gilbert's syndrome
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 1.5 × ULN. For subjects with liver metastases present at baseline, ALT and/or AST = 3 × ULN is permitted.

Renal function:

? Creatinine clearance = 60 mL/min calculated by the Cockcroft-Gault formula using actual body weight (see Table 15) or 24-hour urine collection.

Gender and Reproductive Considerations 8. 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.

9. Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Refer to Appendix 4, Section 10.4 for details and definitions of WOCBP, postmenopausal females and contraception guidance.

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 the methods specified in Section 10.4 for the women along with 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.

Informed Consent 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
Exclusion Criteria

The subject must be excluded from participating in the study if he/she meets any of the following:

Medical Conditions

1. Have not recovered from adverse events (must be Grade = 1) due to prior anti-cancer treatment.
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. 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.

a) QTcF > 480 msec at screening (based on average of triplicate ECGs at baseline).

i. If the QTc is prolonged in a subject with a pacemaker or bundle branch block, the subject may be enrolled in the study if confirmed by the Medical Monitor.
9. Ongoing immune-related/stimulated adverse events (irAEs) from other agents or required permanent discontinuation of prior ICIs due to irAEs. Subjects with resolved irAE may be allowed to enroll following consultation with Sponsor's Medical Monitor (or designee).
10. 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;

Exclusion Criteria

The subject must be excluded from participating in the study if he/she meets any of the following:

Medical Conditions

1. Have not recovered from adverse events (must be Grade = 1) due to prior anti-cancer treatment.
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. 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.

a) QTcF > 480 msec at screening (based on average of triplicate ECGs at baseline).

i. If the QTc is prolonged in a subject with a pacemaker or bundle branch block, the subject may be enrolled in the study if confirmed by the Medical Monitor.
9. Ongoing immune-related/stimulated adverse events (irAEs) from other agents or required permanent discontinuation of prior ICIs due to irAEs. Subjects with resolved irAE may be allowed to enroll following consultation with Sponsor's Medical Monitor (or designee).
10. 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 (e.g., vitiligo, psoriasis, or alopecia);
* Any other disease that is not expected to recur in the absence of external triggering factors.
11. Pregnancy or lactating.
12. A serious nonmalignant disease (e.g., psychiatric, substance abuse, uncontrolled intercurrent illness, etc.) that could compromise protocol objectives in the opinion of the investigator and/or the Sponsor.
13. Any other condition that, in the opinion of the investigator, would prohibit the subject from participating in the study.

Prior Therapy
14. Prior chemotherapy and/or non-biologic targeted therapy within 4 weeks, or biologic targeted therapy, immunotherapy, and/or radiation therapy within 6 weeks prior to Cycle 1 Day 1. Subjects who receive targeted radiation therapy for localized palliative care may be eligible to start treatment < 6 weeks with Medical Monitor agreement.
15. Prior treatment with cemiplimab.
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 live, attenuated, inactivated or research vaccines within 30 days prior to the first dose of IP. Refer to Section 6.9.1 for prohibited vaccines. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed.
19. Prior allogeneic hematopoietic stem cell transplant or solid organ transplant. Prior/Concurrent Clinical Study Experience
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.

Other
21. 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
Active, not 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
31/10/2026
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
Victor Zaporojan, 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
pwatkins@maiabiotech.com
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