A phase 3 study evaluating ociperlimab plus tislelizumab plus cCRT or tislelizumab plus cCRT versus cCRT followed by durvalumab
- Conditions
- Previously Untreated, Locally Advanced, Unresectable Non-Small Cell Lung CancerMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004656-14-ES
- Lead Sponsor
- BeiGene, Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 900
1. Age = 18 years on the day of signing the ICF (or the legal age of consent in the jurisdiction in which the study is taking place).
2. Ability to provide written informed consent and to understand and agree to comply with the requirements of the study and the schedule of assessments.
3. Patient has newly diagnosed, histologically confirmed, locally advanced, Stage III unresectable NSCLC (AJCC Cancer Staging Manual 2017).
a. Tumors of mixed non-small cell histology will be categorized by the predominant cell type; if small cell elements are present, the patient is ineligible.
b. Staging will be confirmed at screening by positron emission tomography (PET)/computed tomography (CT) and brain imaging by magnetic resonance imaging (MRI) or computed tomography (CT) with contrast.
c. Fluorodeoxyglucose (FDG)-PET/CT will be performed for the whole body, or sufficient to rule out distant metastases (eg, from skull base to knees), to exclude distant disease and confirm that patients are in Stage III. If the CT scan portion is with contrast and is of sufficiently high quality, a separate CT scan at screening can be skipped.
d. While centers are encouraged to obtain tissue confirmation of lymph node metastases in N2 or N3 disease, the tumor board/multidisciplinary team in individual cases may dispense with this procedure (AJCC Cancer Staging Manual 2017).
4. Measurable disease as assessed by RECIST v1.1.
5. Patients must submit archival tumor tissue (formalin-fixed paraffin-embedded [FFPE] block containing tumor [preferred] or approximately 15 [at least 6] freshly cut unstained FFPE slides) with an associated pathology report, or agree to a tumor biopsy for determination of PD-L1 expression and other biomarker analyses (Fresh tumor biopsies are strongly recommended at baseline in patients with readily accessible tumor lesions and who consent to the biopsies. An additional = 6 slides are required if EGFR mutation status needs to be tested in a central laboratory). PD-L1 expression in TC will be prospectively assessed via VENTANA PD-L1 (SP263) assay at a central laboratory. Only patients who have evaluable PD-L1 expression results are eligible.
6. ECOG Performance Status of 0 or 1.
7. Patients must have adequate organ function as indicated by the following screening laboratory values obtained within 7 days before the first study treatment:
a. Patients must not have required blood transfusion or growth factor support = 14 days before sample collection at screening for the following:
i. Absolute neutrophil count (ANC) = 1.5 x 109/L
ii. Platelets = 100 x 109/L
iii. Hemoglobin = 90 g/L or = 5.6 mmol /L (Note: Criteria must be met without a transfusion within 14 days of obtaining the sample)
b. Calculated creatinine clearance (CrCl) = 60 mL/min (Cockcroft-Gault formula) for patients receiving cisplatin and = 45 mL/min (Cockcroft-Gault formula) for patients receiving carboplatin or pemetrexed.
c. Serum total bilirubin = 1.5 x upper limit of normal (ULN) (total bilirubin must be < 3 x ULN for patients with Gilbert syndrome).
d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x ULN.
8. Females of childbearing potential must consent to use a highly effective method of birth control for the duration of the study, and for = 120 days after the last dose of ociperlimab and tislelizumab in Arm A or tislelizumab in Arm B, or at least 3 months after the last dose of durvalumab, or at least 180 days after the last dose of chemotherapy or
1. Any prior therapy for lung cancer, including but not limited to chemotherapy, radiotherapy, targeted therapy, biologic therapy, or immunotherapy.
2. Any prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or for breast cancer.
3. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, TIGIT, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
4. Diagnosed with NSCLC that harbors an EGFR-sensitizing mutation or ALK gene translocation.
a. For non-squamous and squamous NSCLC, patients with known EGFR mutation status or ALK translocation who are sensitive to available targeted inhibitor therapy are excluded.
b. For non-squamous NSCLC, patients with unknown EGFR mutation status will be required to undergo a tissue-based EGFR test locally or at a central laboratory before enrollment. Patients with sensitive EGFR mutation status will be excluded. Patients with unknown ALK status may be enrolled.
c. Patients with squamous NSCLC and unknown EGFR mutation or ALK status will not be required to be tested at screening.
5. Any patient for whom the clinician plans to perform neoadjuvant therapy (eg chemotherapy, chemoradiotherapy) followed by definite surgery, or induction therapy (eg chemotherapy) followed by definitive chemoradiotherapy will be considered ineligible.
6. Patient’s radiation treatment plans are likely to encompass a volume of whole lung (total lung volume minus PTV) receiving = 20 Gy in total (V20) of more than 35% of lung volume.
7. Active autoimmune diseases or history of autoimmune diseases that may relapse.
8. Any active malignancy = 2 years before the first dose of study treatment except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively.
9. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication = 14 days before the first dose of study treatment.
10. 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 the first dose of study treatment.
11. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence within 2 weeks of intervention).
12. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases, etc.
13. Infection (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal or antiviral therapy within 14 days before the first dose of study treatment.
14. Untreated chronic hepatitis B or chronic HBV carriers with HBV DNA > 500 IU/mL (or > 2500 copies/mL) at screening.
15. Patients with active hepatitis C.
16. Known history of HIV infection.
17. Any major surgical procedure = 28 days before the first dose of study treatment. Patients must have recovered adequately from the toxicity and/or complications from the intervention before the first dose of study treatment.
18. Prior allogeneic stem cell transplantation or organ transplantation.
19. Any of the following cardiovascular risk factors:
a. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, = 28 days before the first dose of study treatment.
b. Pulmonary embolism = 28 days before the firs
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method