| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Non-Small Cell Lung Cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| Non-Small Cell Lung Cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061873 |
| E.1.2 | Term | Non-small cell lung cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10029519 |
| E.1.2 | Term | Non-small cell lung cancer stage III |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10029522 |
| E.1.2 | Term | Non-small cell lung cancer stage IV |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Primary:
• To determine the safety and tolerability of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC
• To assess the efficacy of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC
|
|
| E.2.2 | Secondary objectives of the trial |
Secondary:
• Additional efficacy evaluation
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
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 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,
are excluded:
• 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 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
x ULN due to Gilbert's syndrome
Alanine aminotransferase (ALT) and aspartate aminotransferase
(AST) ≤ 1.5 xULN. For subjects with liver metastases present at
baseline, ALT and/or AST≤ 3xULN iis permitted.
Renal function: Creatinine clearance ≥ 60 mL/min calculated by the
Cockcroft-Gault formula using actual body weight 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.
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. |
|
| E.4 | Principal exclusion criteria |
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 will 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. 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• Incidence of dose limiting toxicities (DLTs; applicable for Part A and Part C), treatment emergent adverse events (TEAEs), and serious adverse events (SAEs) 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.
• 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
• Disease control rate (DCR) defined as CR, PR or stable disease (SD) as assessed by the investigator based on RECIST v1.1 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| DLTs will be assessed following Part A enrollment and Part C safety lead-in enrollment (if applicable). |
|
| E.5.2 | Secondary end point(s) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| End of study, since no interim analysis is planned according to the protocol |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Bulgaria |
| Czechia |
| Hungary |
| Poland |
| Romania |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
A subject is considered to have completed the study treatment if he/she has completed the EoT
visit. The end of the study is defined as the date of the last subject completed the study, withdrew
informed consent or study closure by Sponsor whichever occurs last. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
Print
