Clinical Trials List
Protocol NumberONO-4538-25
NCT Number(ClinicalTrials.gov Identfier)NCT02582125
2015-07-01 - 2020-12-31
Phase II
Not yet recruiting1
Terminated8
ICD-10C34
Malignant neoplasm of bronchus and lung
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
Multicenter, open-label, single arm, Phase II study in advanced non-small cell lung cancer；Subtitle:A multicenter, open-label, single arm Phase II study to evaluate safety and efficacy of ONO-4538 in stage IIIB/IV or recurrent non-small cell lung cancer patients who are unsuited to radical radiotherapy and resistant to a platinum-base chemotherapeutic regimen.
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Trial Applicant
PROTECH PHARMASERVICES CORPORATION
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Sponsor
ONO Pharmaceutical Co., Ltd.
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Trial scale
Taiwan Multiple Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
3 Not yet recruiting
Audit
CRO
Principal Investigator
Co-Principal Investigator
- 趙東瀛 Division of Thoracic Medicine
- 陳友木 無
- 林孟志 Division of Thoracic Medicine
- 王逸熙 Division of Thoracic Medicine
- 黃國棟 Division of Thoracic Medicine
- 鍾聿修 Division of Thoracic Medicine
- Chia-Cheng Tseng Division of Thoracic Medicine
- 蘇茂昌 Division of Thoracic Medicine
- CHIN-CHOU WANG Division of Thoracic Medicine
- 張晃智 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Chao-Hua Chiu Division of Thoracic Medicine
- 賴信良 Division of Thoracic Medicine
- Jen-Fu Shih Division of Thoracic Medicine
- Yung-Hung Luo Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
13 Completed
Audit
None
Co-Principal Investigator
- KUO-HSUAN HSU Division of Thoracic Medicine
- TSUNG -YING YANG Division of Thoracic Medicine
- 陳焜結 Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- 陳鴻仁 Division of Thoracic Medicine
- 廖偉志 Division of Thoracic Medicine
- Chen Chia-Hung Division of Thoracic Medicine
- Chih-Yen Tu Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Completed
Principal Investigator
Co-Principal Investigator
- Sin-Syue Li Division of General Internal Medicine
- Yu-Min Yeh Division of General Internal Medicine
- Shang-Yin Wu Division of General Internal Medicine
- Wen-Pin Su Division of General Internal Medicine
- Wu-Chou Su Division of General Internal Medicine
- Wei-Pang Chung Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Completed
Principal Investigator
Co-Principal Investigator
- Inn-Wen Chong Division of Thoracic Medicine
- 李玫萱 Division of Thoracic Medicine
- Chih-Jen Yang Division of Thoracic Medicine
- Jen-Yu Hung Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Shih-Hong Li Division of Hematology & Oncology
- 李忠恕 Division of Infectious Disease
- Chih-Liang Wang Division of Hematology & Oncology
- 林倡葦 Division of Infectious Disease
- Kuo-Chin Kao Division of Hematology & Oncology
- 黃世豪 Division of Hematology & Oncology
- 謝任富 Division of Radiology
- Chien-Ying Liu Division of Hematology & Oncology
- Chih-Hung Chen Division of Hematology & Oncology
- Wen-Cheng Chang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
10 Completed
Audit
None
Co-Principal Investigator
- JIN-YUAN SHIH Division of General Internal Medicine
- 陳冠宇 Division of General Internal Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- 林宗哲 Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- Jih-Hsiang Lee Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- 許嘉林 Division of General Internal Medicine
- Chong-Jen Yu Division of General Internal Medicine
- 廖斌志 Division of Hematology & Oncology
- 廖唯昱 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Completed
Audit
None
Condition/Disease
stage IIIB/IV or recurrent non-small cell lung cancer
Objectives
The objective of the study is to investigate the safety and efficacy of ONO-4538 in stage IIIB/IV or recurrent non-small cell lung cancer unsuited to radical radiotherapy and resistant to a platinum-based chemotherapeutic regimen in a multicenter, open-label, single arm study.The primary objective of this study was to investigate the safety of ONO-4538 stage IIIB/IV or recurrent non-small cell lung cancer unsuited to radical radiotherapy and resistant to a platinum-based chemotherapeutic regimen.
Test Drug
Opdivo®
Active Ingredient
Nivolumab
Dosage Form
IV
Dosage
10mg/mL
Endpoints
safety
adverse event
lab
vital sign
ECG
ECOG
efficancy
The objective of the study is to investigate the safety and efficacy of ONO-4538 in stage IIIB/IV or recurrent non-small cell lung cancer unsuited to radical radiotherapy and resistant to a platinum-based chemotherapeutic regimen in a multicenter, open-label, single arm study
adverse event
lab
vital sign
ECG
ECOG
efficancy
The objective of the study is to investigate the safety and efficacy of ONO-4538 in stage IIIB/IV or recurrent non-small cell lung cancer unsuited to radical radiotherapy and resistant to a platinum-based chemotherapeutic regimen in a multicenter, open-label, single arm study
Inclution Criteria
Patients satisfying all the following criteria will be included:
1. Male or female.
2. ≥ 20 years of age (at time of enrollment).
3. Histologically or cytologically confirmed non-small cell lung cancer.
4. Diagnosis of NSCLC in stage IIIB/IV unsuited to radical radiotherapy according to UICC-TNM
classification (7th edition) or recurrent NSCLC.
5. Has at least one measurable lesion, as defined by the RECIST guideline (version 1.1) (Appendix
1), in diagnostic imaging performed 14 or fewer days before enrollment. (Patients who have
received radiotherapy for a measurable lesion must have confirmed progress in diagnostic
imaging following radiotherapy.)
6. Has a history of prior treatment with any of the following systemic anti-cancer products (e.g.,
chemotherapy, molecular targeted therapy, immunotherapy):
1） History of prior platinum-based chemotherapy and up to 1 regimen of prior treatment for
patients negative for or with unknown EGFR activity mutation or ALK gene translocation
2） History of prior platinum-based chemotherapy and an EGFR tyrosine kinase inhibitor, and
up to 2 regimens of prior treatment, for patients positive for EGFR activity mutation
3） History of prior platinum-based chemotherapy and an ALK inhibitor, and up to 2 regimens
of prior treatment, for patients positive for ALK gene translocation
7. ECOG Performance Status (Appendix 2) is 0 to 1.
8. Life expectancy is ≥ 90 days.
9. Women of childbearing potential (including women who are amenorrheic due to chemical
menopause or for another medical reason) must agree to engage in contraception from the time of
informed consent to at least 320 days after the final dose of the investigational product.
10. Men must agree to use a contraceptive from the start of study treatment until at least 320 days
following the last dose of investigational product.
11. Percutaneous oxygen saturation by pulse oximetry performed 7 or fewer days before enrollment
is ≥ 94% in the absence of oxygen supplementation.
12. Most recently determined laboratory values, determined 7 or fewer days before enrollment,
satisfy the criteria listed below. Laboratory testing must be performed with no granulocyte
colony stimulating factor (G-CSF) treatment or blood transfusion having taken place 14 or fewer
days before testing. The following testing will be judged by the results of performed at the
investigative site.
- WBC count ≥ 2,000/mm3
and neutrophil count ≥ 1,500/mm3
- Platelet count ≥ 100,000/mm3
- Hemoglobin ≥ 9.0 g/dL
- AST (GOT) and ALT (GPT) ≤ 3.0 times the upper limit of normal range of each institute (In
the case of patients with liver metastasis, AST (GOT) and ALT (GPT) ≤ 5.0 times the upper limit
of normal range)
- Total bilirubin ≤ 2.0 times the upper limit of normal range of each institute
- Creatinine ≤ 1.5 times the upper limit of normal range of each institute or creatinine clearance
(raw or estimated using Cockcroft/Gault formula) > 45 mL/min
13. Tumor tissue (archival or fresh biopsy specimen) must be available for PD-L1 expression
analysis in this study. For subjects where a fresh biopsy is not feasible, archival tumor material
must be made available.
1. Male or female.
2. ≥ 20 years of age (at time of enrollment).
3. Histologically or cytologically confirmed non-small cell lung cancer.
4. Diagnosis of NSCLC in stage IIIB/IV unsuited to radical radiotherapy according to UICC-TNM
classification (7th edition) or recurrent NSCLC.
5. Has at least one measurable lesion, as defined by the RECIST guideline (version 1.1) (Appendix
1), in diagnostic imaging performed 14 or fewer days before enrollment. (Patients who have
received radiotherapy for a measurable lesion must have confirmed progress in diagnostic
imaging following radiotherapy.)
6. Has a history of prior treatment with any of the following systemic anti-cancer products (e.g.,
chemotherapy, molecular targeted therapy, immunotherapy):
1） History of prior platinum-based chemotherapy and up to 1 regimen of prior treatment for
patients negative for or with unknown EGFR activity mutation or ALK gene translocation
2） History of prior platinum-based chemotherapy and an EGFR tyrosine kinase inhibitor, and
up to 2 regimens of prior treatment, for patients positive for EGFR activity mutation
3） History of prior platinum-based chemotherapy and an ALK inhibitor, and up to 2 regimens
of prior treatment, for patients positive for ALK gene translocation
7. ECOG Performance Status (Appendix 2) is 0 to 1.
8. Life expectancy is ≥ 90 days.
9. Women of childbearing potential (including women who are amenorrheic due to chemical
menopause or for another medical reason) must agree to engage in contraception from the time of
informed consent to at least 320 days after the final dose of the investigational product.
10. Men must agree to use a contraceptive from the start of study treatment until at least 320 days
following the last dose of investigational product.
11. Percutaneous oxygen saturation by pulse oximetry performed 7 or fewer days before enrollment
is ≥ 94% in the absence of oxygen supplementation.
12. Most recently determined laboratory values, determined 7 or fewer days before enrollment,
satisfy the criteria listed below. Laboratory testing must be performed with no granulocyte
colony stimulating factor (G-CSF) treatment or blood transfusion having taken place 14 or fewer
days before testing. The following testing will be judged by the results of performed at the
investigative site.
- WBC count ≥ 2,000/mm3
and neutrophil count ≥ 1,500/mm3
- Platelet count ≥ 100,000/mm3
- Hemoglobin ≥ 9.0 g/dL
- AST (GOT) and ALT (GPT) ≤ 3.0 times the upper limit of normal range of each institute (In
the case of patients with liver metastasis, AST (GOT) and ALT (GPT) ≤ 5.0 times the upper limit
of normal range)
- Total bilirubin ≤ 2.0 times the upper limit of normal range of each institute
- Creatinine ≤ 1.5 times the upper limit of normal range of each institute or creatinine clearance
(raw or estimated using Cockcroft/Gault formula) > 45 mL/min
13. Tumor tissue (archival or fresh biopsy specimen) must be available for PD-L1 expression
analysis in this study. For subjects where a fresh biopsy is not feasible, archival tumor material
must be made available.
Exclusion Criteria
Patients satisfying any of the following criteria will be excluded:
1. Current or prior severe hypersensitivity to another antibody product.
2. Adverse drug reactions due to prior treatments or remaining effects of surgical therapy that, in
the principal or sub investigator’s opinion, may interfere with the safety evaluation of the
investigational product.
3. Active autoimmune disease or history of chronic or recurring autoimmune disease (Appendix 3).
4. Current or prior interstitial lung disease or pulmonary fibrosis diagnosed based on diagnostic
imaging or clinical findings. (Radiation pneumonitis allows to be enrolled as long as not acute
phase with fibrosis.)
5. Active diverticulitis or symptomatic gastrointestinal ulcerative disease.
6. Multiple primary cancers (except for completely resected basal cell cancer, stage I squamous cell
carcinoma, carcinoma in situ, intramucosal carcinoma, or superficial bladder cancer or any other
cancer from which the patient has been recurrence-free for at least 5 years).
7. Metastases to the brain or meninges (unless such lesions are asymptomatic and do not require
treatment).
8. Pericardial effusion, pleural effusion, or ascites requiring treatment.
9. Pain associated with bone metastases and others not controllable with a fixed regimen of an
analgesic.
10. History of transient ischemic attack, cerebrovascular accident, thrombosis, or thromboembolism
(pulmonary arterial embolism or deep vein thrombosis) within 180 days of enrollment.
11. Any of the following cardiovascular diseases that are uncontrollable or severe:
- Myocardial infarction within 180 days of enrollment
- Uncontrollable angina pectoris within 180 days of enrollment
- New York Heart Association (NYHA) Grade III or IV congestive cardiac failure
- Hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mmHg
persisting for ≥ 24 hours) despite appropriate treatment
- Arrhythmia requiring treatment
12. On anticoagulant therapy (other than antiplatelet therapy with low-dose aspirin) or having a
disease requiring anticoagulant therapy.
13. Uncontrollable diabetes.
14. Has received a systemic corticosteroid (unless temporarily for testing, prophylaxis, or a similar
purpose unrelated to an autoimmune disease) or an immune suppressant 28 or fewer days before
enrollment.
15. Has received an anti-cancer product (e.g., chemotherapy, molecular targeted therapy (except for
tyrosine kinase inhibitor), and immunotherapy) 28 or fewer days before enrollment or a tyrosine
kinase inhibitor 14 or few days before enrollment.
16. Has undergone surgery for pleural, pericardial, or similar adhesion 28 or fewer days before
enrollment.
17. Has undergone surgical treatment accompanying general anesthesia 28 or fewer days before
enrollment.
18. Has undergone surgical treatment accompanying local or surface anesthesia 14 or fewer days
before enrollment.
19. Has received radiotherapy (except for palliative local radiotherapy) 28 or fewer days before
enrollment, palliative local radiotherapy 14 or few days before enrollment or thoracic
radiotherapy or a radiopharmaceutical agent (except when the radiopharmaceutical agent is used
for testing or diagnostic purposes) 56 or fewer days before enrollment.
20. Has undergone gamma knife or CyberKnife treatment 14 or fewer days before enrollment.
21. Has not resolution to Grade ≤1 by the National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events (CTCAE) ver. 4.0 of all toxic effects of prior tyrosin kinase inhibitor
therapy and palliative local radiotherapy.
22. Has a systemic infection that requires treatment.
23. Has tested positive for HIV-1 antibody, HIV-2 antibody, HTLV-1 antibody, HBs antigen, or
HCV antibody.
24. Has tested positive for HBs antibody or HBc antibody unless patients has a result of undetectable
in HBV-DNA assay despite testing negative for HBs antigen.
25. Is pregnant, nursing, or possibly pregnant.
26. Has received another investigational product 28 or fewer days before enrollment.
27. Has previously received ONO-4538 (MDX-1106 or BMS-936558), an anti-CTLA-4 antibody,
anti-PD-1 antibody, anti-PD-L1 antidody, or other antibody therapy or drug therapy intended to
regulate T-cells.
28. Is found incapable of giving consent due to dementia or another such condition.
29. Patients otherwise found by the principal or sub investigator to be ineligible.
1. Current or prior severe hypersensitivity to another antibody product.
2. Adverse drug reactions due to prior treatments or remaining effects of surgical therapy that, in
the principal or sub investigator’s opinion, may interfere with the safety evaluation of the
investigational product.
3. Active autoimmune disease or history of chronic or recurring autoimmune disease (Appendix 3).
4. Current or prior interstitial lung disease or pulmonary fibrosis diagnosed based on diagnostic
imaging or clinical findings. (Radiation pneumonitis allows to be enrolled as long as not acute
phase with fibrosis.)
5. Active diverticulitis or symptomatic gastrointestinal ulcerative disease.
6. Multiple primary cancers (except for completely resected basal cell cancer, stage I squamous cell
carcinoma, carcinoma in situ, intramucosal carcinoma, or superficial bladder cancer or any other
cancer from which the patient has been recurrence-free for at least 5 years).
7. Metastases to the brain or meninges (unless such lesions are asymptomatic and do not require
treatment).
8. Pericardial effusion, pleural effusion, or ascites requiring treatment.
9. Pain associated with bone metastases and others not controllable with a fixed regimen of an
analgesic.
10. History of transient ischemic attack, cerebrovascular accident, thrombosis, or thromboembolism
(pulmonary arterial embolism or deep vein thrombosis) within 180 days of enrollment.
11. Any of the following cardiovascular diseases that are uncontrollable or severe:
- Myocardial infarction within 180 days of enrollment
- Uncontrollable angina pectoris within 180 days of enrollment
- New York Heart Association (NYHA) Grade III or IV congestive cardiac failure
- Hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mmHg
persisting for ≥ 24 hours) despite appropriate treatment
- Arrhythmia requiring treatment
12. On anticoagulant therapy (other than antiplatelet therapy with low-dose aspirin) or having a
disease requiring anticoagulant therapy.
13. Uncontrollable diabetes.
14. Has received a systemic corticosteroid (unless temporarily for testing, prophylaxis, or a similar
purpose unrelated to an autoimmune disease) or an immune suppressant 28 or fewer days before
enrollment.
15. Has received an anti-cancer product (e.g., chemotherapy, molecular targeted therapy (except for
tyrosine kinase inhibitor), and immunotherapy) 28 or fewer days before enrollment or a tyrosine
kinase inhibitor 14 or few days before enrollment.
16. Has undergone surgery for pleural, pericardial, or similar adhesion 28 or fewer days before
enrollment.
17. Has undergone surgical treatment accompanying general anesthesia 28 or fewer days before
enrollment.
18. Has undergone surgical treatment accompanying local or surface anesthesia 14 or fewer days
before enrollment.
19. Has received radiotherapy (except for palliative local radiotherapy) 28 or fewer days before
enrollment, palliative local radiotherapy 14 or few days before enrollment or thoracic
radiotherapy or a radiopharmaceutical agent (except when the radiopharmaceutical agent is used
for testing or diagnostic purposes) 56 or fewer days before enrollment.
20. Has undergone gamma knife or CyberKnife treatment 14 or fewer days before enrollment.
21. Has not resolution to Grade ≤1 by the National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events (CTCAE) ver. 4.0 of all toxic effects of prior tyrosin kinase inhibitor
therapy and palliative local radiotherapy.
22. Has a systemic infection that requires treatment.
23. Has tested positive for HIV-1 antibody, HIV-2 antibody, HTLV-1 antibody, HBs antigen, or
HCV antibody.
24. Has tested positive for HBs antibody or HBc antibody unless patients has a result of undetectable
in HBV-DNA assay despite testing negative for HBs antigen.
25. Is pregnant, nursing, or possibly pregnant.
26. Has received another investigational product 28 or fewer days before enrollment.
27. Has previously received ONO-4538 (MDX-1106 or BMS-936558), an anti-CTLA-4 antibody,
anti-PD-1 antibody, anti-PD-L1 antidody, or other antibody therapy or drug therapy intended to
regulate T-cells.
28. Is found incapable of giving consent due to dementia or another such condition.
29. Patients otherwise found by the principal or sub investigator to be ineligible.
The Estimated Number of Participants
-
Taiwan
50 participants
-
Global
0 participants
