Clinical Trials List
Protocol NumberCA209-816
NCT Number(ClinicalTrials.gov Identfier)NCT02998528
Completed
2017-09-01 - 2027-03-09
Phase III
Terminated4
ICD-10C34
Malignant neoplasm of bronchus and lung
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
Randomized, Open-Label, Phase 3 Trial of Nivolumab plus Ipilimumab or Nivolumab plus Platinum-Doublet Chemotherapy versus Platinum-Doublet Chemotherapy in Early Stage NSCLC
-
Trial Applicant
BRISTOL-MYERS SQUIBB (TAIWAN) LTD.
-
Sponsor
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- TSUNG -YING YANG Division of Thoracic Medicine
- 陳焜結 Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Kai-Ling Lee Division of Hematology & Oncology
- Huey-En Tzeng Division of Hematology & Oncology
- CHIA-CHUN KUO Division of Hematology & Oncology
- Yu-Min Liao Division of Hematology & Oncology
- Hsin-Lun Lee Division of Hematology & Oncology
- 禚靖 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
2 Terminated
Audit
None
Co-Principal Investigator
- Tzu-Tao Chen Division of Hematology & Oncology
- Ching-Shan Luo Division of Hematology & Oncology
- Po-Hao Feng Division of Hematology & Oncology
- Kuang-Tai Kuo Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
1 Terminated
Audit
CRO
Co-Principal Investigator
- 周德盈 Division of Thoracic Medicine
- 趙恒勝 Division of Thoracic Medicine
- Chao-Hua Chiu Division of Thoracic Medicine
- Yu-Chung Wu Division of Thoracic Medicine
- Heng-Sheng Chao Division of Thoracic Medicine
- Yung-Hung Luo Division of Thoracic Medicine
- 黃建勝 Division of Thoracic Medicine
- Hsu-ching Huang Division of Hematology & Oncology
- 蕭慈慧 Division of Thoracic Medicine
- Yi-Chen Yeh Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
2 Terminated
Audit
None
Condition/Disease
Melanoma, metastatic
Objectives
Primary Objectives:
1. To compare the event-free survival (EFS) by blinded independent central review (BICR) in participants receiving nivolumab plus platinum doublet chemotherapy vs participants receiving platinum doublet chemotherapy in operable stage IB ( 4 cm), II, or resectable IIIA (N2) NSCLC
2. To compare the pathologic complete response (pCR) rate in participants receiving nivolumab plus platinum doublet chemotherapy vs participants receiving platinum doublet chemotherapy in operable stage IB ( 4 cm), II, or resectable IIIA (N2) NSCLC
Secondary Objectives:
1. To assess the major pathologic response (MPR) rate by BIPR of participants receiving nivolumab plus platinum doublet chemotherapy vs participants receiving platinum doublet chemotherapy in operable stage IB ( 4 cm), II, or resectable IIIA (N2) NSCLC
2. To compare the OS of participants receiving nivolumab plus platinum doublet chemotherapy vs participants receiving platinum doublet chemotherapy in operable stage IB ( 4 cm), II, or resectable IIIA (N2) NSCLC
3. To assess the time to death or distant metastases (TTDM) of participants receiving nivolumab plus platinum doublet chemotherapy vs participants receiving platinum doublet chemotherapy in operable stage IB ( 4 cm), II, or resectable IIIA (N2) NSCLC
Test Drug
NIVOLUMAB SINJ 100MG(1VLX10); IPILIMUMAB SINJ200MG(1VLX4)
Active Ingredient
Dosage Form
Solution for Injection
Solution for Injection
Solution for Injection
Dosage
10mg/mL
5mg/mL
5mg/mL
Endpoints
Primary Endpoints:
1. EFS defined as the length of time from randomization to any of the following events: any progression of disease precluding
surgery, progression or recurrence disease (based on BICR assessment per RECIST 1.1) after surgery, or death due to any cause.
Participants who don’t undergo surgery for reason other than progression will be considered to have an event at RECIST 1.1
(based on BICR) progression or death.
2. pCR rate is defined as number of randomized participants with absence of residual tumor in lung and lymph nodes as evaluated by blinded independent pathological review (BIPR), divided by the number of randomized participants for each treatment group.
Secondary Endpoints:
1. MPR rate, defined as number of randomized participants with 10% residual tumor in lung and lymph nodes as evaluated by BIPR, divided by the number of randomized participants for each treatment group. Viable tumors in situ carcinoma should not be included in MPR calculation.
2. OS is defined as the time between the date of randomization and the date of death. OS will be censored on the last date a participant was known to be alive.
3. TTDM is defined as the time between the date of randomization and the first date of distant metastasis or the date of death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is outside of the thorax using BICR according to RECIST 1.1. Patients who have not developed distant metastasis or died at the time of analysis will be censored on the date of their last evaluable tumor assessment.
1. EFS defined as the length of time from randomization to any of the following events: any progression of disease precluding
surgery, progression or recurrence disease (based on BICR assessment per RECIST 1.1) after surgery, or death due to any cause.
Participants who don’t undergo surgery for reason other than progression will be considered to have an event at RECIST 1.1
(based on BICR) progression or death.
2. pCR rate is defined as number of randomized participants with absence of residual tumor in lung and lymph nodes as evaluated by blinded independent pathological review (BIPR), divided by the number of randomized participants for each treatment group.
Secondary Endpoints:
1. MPR rate, defined as number of randomized participants with 10% residual tumor in lung and lymph nodes as evaluated by BIPR, divided by the number of randomized participants for each treatment group. Viable tumors in situ carcinoma should not be included in MPR calculation.
2. OS is defined as the time between the date of randomization and the date of death. OS will be censored on the last date a participant was known to be alive.
3. TTDM is defined as the time between the date of randomization and the first date of distant metastasis or the date of death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is outside of the thorax using BICR according to RECIST 1.1. Patients who have not developed distant metastasis or died at the time of analysis will be censored on the date of their last evaluable tumor assessment.
Inclution Criteria
1) Signed Written Informed Consent
a) Participants must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care.
b) Participants must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
2) Type of Participant and Target Disease Characteristics
a) Eastern Cooperative Group (ECOG) Performance Status 0-1 (Appendix 3)
b) Participants with histologically confirmed Stage IB ( 4 cm), II, IIIA (N2) NSCLC (per the 7th International Association for the Study of Lung Cancer) with disease that is considered resectable.49
c) Measurable disease according to RECIST version 1.1
d) Participants must have a tumor tissue sample available for PD-L1 IHC testing performed by a third-party analyzing lab during the screening period:
i) Either a formalin-fixed, paraffin-embedded (FFPE) tissue block or unstained tumor tissue sections, with an associated pathology report, must be submitted for biomarker evaluation prior to randomization. The tumor tissue sample may be fresh or archival if obtained within 3 months prior to enrollment.
ii) Tissue must be a core needle biopsy, excisional or incisional biopsy. Fine needle biopsies obtained by EBUS is not considered adequate for biomarker review and randomization. Core needle biopsies obtained by EBUS are acceptable for randomization.
e) Absence of major associated pathologies that increase the surgery risk to an unacceptable level
f) All suspicious mediastinal lymph nodes including those that are pathologically enlarged or FDG avid on PET/CT require further sampling for pathological confirmation of accessible by mediastinoscopy, thoracoscopy, or EBUS.
g) Pulmonary function capacity capable of tolerating the proposed lung resection according to the surgeon.
3) Age and Reproductive Status
a) Males and Females, ages ove 18 or age of majority
b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment.
c) Women must not be breastfeeding
d) Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception (Appendix 6) for the duration of treatment with nivolumab and 5 months after the last dose of study treatment (ie, 30 days [duration of ovulatory cycle]) plus the time required for the investigational drug to undergo approximately 5 half-lives (for participants treated in Arm A).
e) WOCBP must also agree to follow instructions for method(s) of contraception from the time of enrollment for the duration of treatment with chemotherapy plus 5 half-lives of chemotherapy plus 30 days (duration of ovulatory cycle) for a total of 30 days post-treatment completion or a duration specified by the local labels of the chemotherapy drugs received, whichever is longer (for participants treated in Arm B).
f) Males who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception (Appendix 6) for the duration of treatment with nivolumab and 7 months after the last dose of study treatment (ie, 90 days [duration of sperm turnover] plus the time required for the investigational drug to undergo approximately 5 half-lives)
(for participants treated in Arm A). In addition, male participants must be willing to refrain from sperm donation during this time.
g) Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) with chemotherapy plus 5 half-lives of the study treatment plus 90 days (duration of sperm turnover) for a total of 90 days post-treatment completion or a duration specified by the local labels of the chemotherapy drugs received, whichever is longer (participants in Arm B). In addition, male participants must be willing to refrain from sperm donation during this time.
h) Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section. Investigators shall counsel WOCBP, and male participants who are sexually active with WOCBP, on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly effective methods of contraception, which have a failure rate of < 1% when used consistently and correctly.
a) Participants must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care.
b) Participants must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
2) Type of Participant and Target Disease Characteristics
a) Eastern Cooperative Group (ECOG) Performance Status 0-1 (Appendix 3)
b) Participants with histologically confirmed Stage IB ( 4 cm), II, IIIA (N2) NSCLC (per the 7th International Association for the Study of Lung Cancer) with disease that is considered resectable.49
c) Measurable disease according to RECIST version 1.1
d) Participants must have a tumor tissue sample available for PD-L1 IHC testing performed by a third-party analyzing lab during the screening period:
i) Either a formalin-fixed, paraffin-embedded (FFPE) tissue block or unstained tumor tissue sections, with an associated pathology report, must be submitted for biomarker evaluation prior to randomization. The tumor tissue sample may be fresh or archival if obtained within 3 months prior to enrollment.
ii) Tissue must be a core needle biopsy, excisional or incisional biopsy. Fine needle biopsies obtained by EBUS is not considered adequate for biomarker review and randomization. Core needle biopsies obtained by EBUS are acceptable for randomization.
e) Absence of major associated pathologies that increase the surgery risk to an unacceptable level
f) All suspicious mediastinal lymph nodes including those that are pathologically enlarged or FDG avid on PET/CT require further sampling for pathological confirmation of accessible by mediastinoscopy, thoracoscopy, or EBUS.
g) Pulmonary function capacity capable of tolerating the proposed lung resection according to the surgeon.
3) Age and Reproductive Status
a) Males and Females, ages ove 18 or age of majority
b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment.
c) Women must not be breastfeeding
d) Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception (Appendix 6) for the duration of treatment with nivolumab and 5 months after the last dose of study treatment (ie, 30 days [duration of ovulatory cycle]) plus the time required for the investigational drug to undergo approximately 5 half-lives (for participants treated in Arm A).
e) WOCBP must also agree to follow instructions for method(s) of contraception from the time of enrollment for the duration of treatment with chemotherapy plus 5 half-lives of chemotherapy plus 30 days (duration of ovulatory cycle) for a total of 30 days post-treatment completion or a duration specified by the local labels of the chemotherapy drugs received, whichever is longer (for participants treated in Arm B).
f) Males who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception (Appendix 6) for the duration of treatment with nivolumab and 7 months after the last dose of study treatment (ie, 90 days [duration of sperm turnover] plus the time required for the investigational drug to undergo approximately 5 half-lives)
(for participants treated in Arm A). In addition, male participants must be willing to refrain from sperm donation during this time.
g) Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) with chemotherapy plus 5 half-lives of the study treatment plus 90 days (duration of sperm turnover) for a total of 90 days post-treatment completion or a duration specified by the local labels of the chemotherapy drugs received, whichever is longer (participants in Arm B). In addition, male participants must be willing to refrain from sperm donation during this time.
h) Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section. Investigators shall counsel WOCBP, and male participants who are sexually active with WOCBP, on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly effective methods of contraception, which have a failure rate of < 1% when used consistently and correctly.
Exclusion Criteria
1) Medical Conditions
a) Presence of locally advanced unresectable (regardless of stage) or metastatic disease
(stage IV).
b) Participants with known EGFR mutations or ALK translocation. If testing is done, an FDA-approved assay should be used, and testing will be performed locally.
c) Participants with brain metastases are excluded from this study, and all participants with stage II or higher disease and those with suspicion of brain metastases should have MRI or CT of the brain with contrast 28 days prior to randomization.
d) Participants with Grade 2 peripheral neuropathy
e) Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not
expected to recur in the absence of an external trigger are permitted to enroll.
f) Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active
autoimmune disease
g) Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally.
h) Participants with serious or uncontrolled medical disorders
2) Prior/Concomitant Therapy
a) Administration of chemotherapy or any other cancer therapy in the pre-operative period.
b) Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody or any other antibody targeting T cell co-regulatory pathways.
3) Physical and Laboratory Test Findings
a) Screening laboratory values must meet the following criteria (using CTCAE v4):
i) WBC < 2000/L
ii) Neutrophils 1500/L
iii) Platelets < 100x103/L
iv) Hemoglobin 9.0 g/dL
v) Serum creatinine 1.5 x ULN or calculated creatinine clearance (CrCl) < 50 mL/min
(using the Cockcroft-Gault formula)
Female CrCl = (140- age in years) x weight in kg x 0.85
72 x serum creatinine in mg/ dL
Male CrCl = (140- age in years) x weight in kg x 1.00
72 x serum creatinine in mg/ dL
vi) AST > 3.0 x ULN
vii) ALT 3.0 x ULN
viii) Total Bilirubin 1.5 x ULN (except participants with Gilbert Syndrome who must
have a total bilirubin level of < 3.0 x ULN).
b) Participants with active hepatitis B (positive hepatitis B surface antigen [HBsAg] or
hepatitis C virus (HCV) (positive HCV RNA)
i) Participants with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and the absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to randomization. HBV carriers or those participants requiring antiviral therapy are not eligible to participate.
ii) Participants positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
c) Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
d) Excluding participants with serious or uncontrolled medical disorders
4) Allergies and Adverse Drug Reaction
a) History of allergy or hypersensitivity to study drug components
5) Other Exclusion Criteria
a) Prisoners or participants who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a participant. Strict conditions apply and Bristol-Myers Squibb approval is required.
b) Participants who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
Eligibility criteria for this study have been carefully considered to ensure the safety of the study participants and that the results of the study can be used. It is imperative that participants fully meet all eligibility criteria.
a) Presence of locally advanced unresectable (regardless of stage) or metastatic disease
(stage IV).
b) Participants with known EGFR mutations or ALK translocation. If testing is done, an FDA-approved assay should be used, and testing will be performed locally.
c) Participants with brain metastases are excluded from this study, and all participants with stage II or higher disease and those with suspicion of brain metastases should have MRI or CT of the brain with contrast 28 days prior to randomization.
d) Participants with Grade 2 peripheral neuropathy
e) Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not
expected to recur in the absence of an external trigger are permitted to enroll.
f) Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active
autoimmune disease
g) Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally.
h) Participants with serious or uncontrolled medical disorders
2) Prior/Concomitant Therapy
a) Administration of chemotherapy or any other cancer therapy in the pre-operative period.
b) Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody or any other antibody targeting T cell co-regulatory pathways.
3) Physical and Laboratory Test Findings
a) Screening laboratory values must meet the following criteria (using CTCAE v4):
i) WBC < 2000/L
ii) Neutrophils 1500/L
iii) Platelets < 100x103/L
iv) Hemoglobin 9.0 g/dL
v) Serum creatinine 1.5 x ULN or calculated creatinine clearance (CrCl) < 50 mL/min
(using the Cockcroft-Gault formula)
Female CrCl = (140- age in years) x weight in kg x 0.85
72 x serum creatinine in mg/ dL
Male CrCl = (140- age in years) x weight in kg x 1.00
72 x serum creatinine in mg/ dL
vi) AST > 3.0 x ULN
vii) ALT 3.0 x ULN
viii) Total Bilirubin 1.5 x ULN (except participants with Gilbert Syndrome who must
have a total bilirubin level of < 3.0 x ULN).
b) Participants with active hepatitis B (positive hepatitis B surface antigen [HBsAg] or
hepatitis C virus (HCV) (positive HCV RNA)
i) Participants with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and the absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to randomization. HBV carriers or those participants requiring antiviral therapy are not eligible to participate.
ii) Participants positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
c) Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
d) Excluding participants with serious or uncontrolled medical disorders
4) Allergies and Adverse Drug Reaction
a) History of allergy or hypersensitivity to study drug components
5) Other Exclusion Criteria
a) Prisoners or participants who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a participant. Strict conditions apply and Bristol-Myers Squibb approval is required.
b) Participants who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
Eligibility criteria for this study have been carefully considered to ensure the safety of the study participants and that the results of the study can be used. It is imperative that participants fully meet all eligibility criteria.
The Estimated Number of Participants
-
Taiwan
16 participants
-
Global
0 participants
