| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Previously treated Non−Small Cell Lung Cancer in the second or third line setting. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Previously treated Non−Small Cell Lung Cancer in the second or third line setting. |
|
| 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.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To compare the efficacy, as measured by overall survival (OS), of tislelizumab with docetaxel in the second- or third-line setting in patients with non-small cell lung cancer (NSCLC) who have progressed on a prior platinum-containing regimen. A comparison of the treatment arms will be performed in:
o The intent-to-treat (ITT) analysis set
o The program cell death protein ligand-1 (PD-L1) positive analysis set, where PD-L1 positive is defined as ≥25% of tumor cells (TCs) with PD-L1 membrane staining via the Ventana SP263 assay |
|
| E.2.2 | Secondary objectives of the trial |
1. To compare the efficacy of tislelizumab and docetaxel as measured by objective response rate (ORR), duration of response (DoR), and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in:
o The ITT population
o The PD-L1 positive analysis set
2. To compare health-related quality of life (HRQoL) between tislelizumab and docetaxel
3. To evaluate the safety and tolerability of tislelizumab versus docetaxel |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Able to provide written informed consent and can understand and
comply with the requirements of the study and the schedule of
assessments.
2. Age ≥ 18 years on the day of signing the informed consent form (or
the legal age of consent in the jurisdiction in which the study is taking place).
3. Histologically confirmed disease which is currently locally advanced or
metastatic NSCLC of either squamous or non-squamous histology.
4. With disease progression during or following treatment with at least
one platinum-containing regimen.
• Patients who received prior neo-adjuvant or adjuvant chemotherapy
but progressed within 6 months after last dose are eligible provided the
target lesion(s) have not been previously treated with local therapy
(radiation) or the target lesion(s) within the field of local therapy have
subsequently progressed as defined per RECIST v1.1
• Anti-EGFR treatment with disease progression as the treatment
outcome is counted as a line of therapy.
• Anticancer agents used for pleurodesis are not counted as a line of
therapy.
5. Patients must be able to provide archival/fresh tumor tissues (FFPE
blocks or approximately 11 [at least 5] freshly cut unstained FFPE
slides) for biomarker analysis to assess PD-L1 expression and, provided
sufficient tissue, including tumor mutational burden (TMB), and gene
expression profiling (GEP). Documentation of wild type status of EGFR
by tissue-based test must be provided for patients with non-squamous
NSCLC prior to enrollment. For undocumented cases, archival/fresh
tumor tissues (FFPE blocks or 6 freshly cut unstained FFPE slides) are
required for central assessment of EGFR mutation. In the absence of
archival tumor tissues, a fresh biopsy of a tumor lesion at baseline
(within 42 days before Cycle 1 Day 1) is mandatory (written informed
consent is required prior to fresh tumor biopsies)..
6. ECOG PS ≤1.
7. Adequate hematologic and end-organ function, as defined by the
following laboratory results (obtained ≤28 days prior to randomization):
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelets ≥ 100 ×
109/L, and hemoglobin ≥ 90 g/L. Note: Patients must not have required
a blood transfusion or growth factor support within the 14 days before
sample collection
• Estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73m2 by
Chronic Kidney Disease Epidemiology Collaboration equation (Appendix
6)
• Total serum bilirubin ≤1.5 × upper limit of normal (ULN)
- ≤3 × ULN, if Gilbert's syndrome or if indirect bilirubin concentrations
are suggestive of extrahepatic source of the elevation
• Aspartate and alanine aminotransferase (AST and ALT) ≤3 × ULN
- ≤5 × ULN, if liver metastases
8. Females of childbearing potential must be willing to practice highly
effective method of birth control (Appendix 4) for the duration of the
study, and, for patients in Arm A, for at least 120 days after the last dose
of tislelizumab, and have a negative urine or serum pregnancy test
within 7 days of randomization.
9. Non-sterile males must be willing to use a highly effective method of
birth control for the duration of the study and, for patients in Arm A, for
at least 120 days after the last dose of tislelizumab.
10. Expected life span > 12 weeks. |
|
| E.4 | Principal exclusion criteria |
1. Received prior docetaxel treatment for metastatic disease or prior
immune checkpoint inhibitor therapies targeting PD-1, PD-L1 or CTLA-4.
2. Diagnosed with NSCLC that harbors EGFR sensitizing or driver
mutation or ALK gene translocation.
3. Patients with toxicities (as a result of prior anticancer therapy including radiation) which
have not recovered to baseline or stabilized except for AEs not
constituting a likely safety risk including but not limited to alopecia,
rash, pigmentation, specific laboratory abnormalities etc.
4. Received chemotherapy, immunotherapy (eg, interleukin, interferon,
thymoxin), or investigational agent, used to control cancer ≤ 28 days (or
≤ 5 half lives, whichever is shorter) prior to randomization
5. Received any herbal medicine used to control cancer within 14 days
prior to randomization.
6. History of severe hypersensitivity reactions to other mAbs.
7. History of interstitial lung disease, non-infectious pneumonitis or
uncontrolled systemic diseases, including diabetes, hypertension,
pulmonary fibrosis, acute lung diseases, etc.
8. Patients with significantly impaired pulmonary function, or who
require supplemental oxygen at baseline.
9. Clinically significant pericardial effusion.
10. Clinically uncontrolled pleural effusion or ascites that requires
pleurocentesis or abdominal tapping for drainage within 2 weeks prior to
randomization.
11. Active Leptomeningeal disease or uncontrolled, untreated brain
metastasis as per protocol
12. Major surgical procedure requiring general anesthesia, or significant
traumatic injury ≤ 28 days prior to randomization, or anticipation of
need for major surgical procedure during the course of the study.
•Placement of vascular access device is not considered major surgery.
13. Malignancy other than NSCLC
14. Severe chronic or active infections (including tuberculosis infection)
requiring systemic antibacterial, antifungal, antiviral therapy, or
systemic oral/IV antibiotics within 14 days prior to randomization.
• Severe infections within 4 weeks prior to randomization, including but
not limited to hospitalization for complications of infection, bacteremia,
or severe pneumonia.
15. A known history of human immunodeficiency virus (HIV) infection.
16. Patients with active/symptomatic carrier or chronic hepatitis B virus
(HBV) whose HBV DNA ≥ 500 IU/mL (or ≥ 2500 copies/mL) should be
excluded.
17. Active autoimmune diseases or history of autoimmune diseases that
may relapse should be excluded.
18. Requiring systemic treatment with either corticosteroids (>10 mg
daily prednisone or equivalent) or other immunosuppressive medications
within 14 days of randomization.
19. With uncontrolled diabetes or > Grade 1 laboratory test
abnormalities in potassium, sodium, or corrected calcium despite
standard medical management or ≥ Grade 3 hypoalbuminemia ≤ 14 days
before randomization.
20. Any of the following cardiovascular criteria:
• Cardiac chest pain, defined as moderate pain that limits instrumental
activities of daily living, ≤ 28 days before randomization.
• Symptomatic pulmonary embolism ≤ 28 days before randomization.
• Acute myocardial infarction ≤ 6 months prior to randomization.
• Heart failure of New York Heart Association Classification III or IV
(see Appendix 5) ≤6 months prior to randomization
• Grade ≥2 ventricular arrhythmia ≤6 months prior to randomization
• Cerebral vascular accident or transient ischemic attack ≤ 6 months
prior to randomization.
• Uncontrolled hypertension: systolic pressure ≥ 160 mmHg or diastolic
pressure ≥ 100 mmHg despite anti-hypertension medications ≤ 28 days
before randomization.
• Any episode of syncope or seizure ≤ 28 days before randomization.
21. Prior allogeneic stem cell transplantation or organ transplantation.
22. Was administered a live vaccine ≤ 4 weeks before randomization.
Note: Seasonal vaccines for influenza are generally inactivated vaccines
and are allowed. Intranasal vaccines are live vaccines, and are not
allowed ≤ 4 weeks before randomization.
23. Underlying medical conditions (including laboratory abnormalities)
or alcohol or drug abuse or dependence that, will be unfavorable for the
administration of study drug or affect the explanation of drug toxicity or
AEs or result in insufficient or impaired compliance with study conduct.
24. Concurrent participation in another therapeutic clinical study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
OS - defined as the time from the date of randomization to the date of
death due to any cause in the ITT and PD-L1 positive analysis set. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• ORR – defined as the proportion of patients in the ITT and PD-L1 positive analysis set who had a CR or PR as assessed by the investigator per RECIST v1.1
• DoR – defined as the time from the first occurrence of a documented objective response to the time of relapse, as determined by the investigator per RECIST v1.1, or death from any cause, whichever comes first, in the ITT and PD-L1 positive analysis set
• PFS – defined as the time from the date of randomization to the date of the first objectively documented tumor progression as assessed by the investigator per RECIST v1.1 or death from any cause, whichever occurs first, in the ITT and PD-L1 positive analysis set
• HRQoL – measured using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) and Core 30 (EORTC QLQ-C30), and European Quality of Life 5-Dimensions, 5-level (EQ-5D-5L) scale
• Incidence and severity of TEAEs graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), v4.03 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 60 |
| 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 |
| Brazil |
| China |
| Mexico |
| New Zealand |
| Lithuania |
| Poland |
| Bulgaria |
| Russian Federation |
| Slovakia |
| Turkey |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| 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 | 9 |
| 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 | 9 |
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