Clinical Trials List
Protocol NumberCA017-078
NCT Number(ClinicalTrials.gov Identfier)NCT03661320
Active
2019-05-19 - 2027-01-25
Phase III
Recruiting4
ICD-10C67.0
Malignant neoplasm of trigone of bladder
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9188.0
Malignant neoplasm of trigone of urinary bladder
A Phase 3, Randomized, Study of Neoadjuvant Chemotherapy Alone Versus Neoadjuvant Chemotherapy Plus Nivolumab or Nivolumab and BMS-986205, Followed by Continued Post- Surgery Therapy With Nivolumab or Nivolumab and BMS-986205 in Participants With Muscle- Invasive Bladder Cancer
-
Trial Applicant
BRISTOL-MYERS SQUIBB (TAIWAN) LTD.
-
Sponsor
Bristol-Myers Squibb
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Yi-Hsiu Huang Division of Urology
- Mu-Hsin Chang Division of Urology
- Chih-Chieh Lin Division of Urology
- Hsiao-Jen Chung Division of Urology
- 潘競成 Division of Urology
- Jiun-I Lai Division of Urology
- Yen-Hwa Chang Division of Urology
- Chueh-Chuan Yen Division of Urology
- Tzu-chun Wei Division of Urology
- 沈書慧 Division of Urology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Shian-Shiang Wang Division of Urology
- Chia-Yen Lin Division of Urology
- 熊小澐 Division of Radiology
- 廖博崎 Division of Urology
- 洪晟鈞 Division of Urology
- Jian-Ri Li Division of Urology
- 賴谷順 Division of Urology
- 裘坤元 Division of Urology
- 盧嘉文 Division of Urology
- 洪啟峰 Division of Urology
- JU-CHUAN HU Division of Urology
- Cheng-Kuang Yang Division of Urology
- 王樹吉 Division of Urology
- Cheng-Che Chen Division of Urology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- - - Division of Hematology & Oncology
- 洪士鈞 Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
- Yeong-Shiau Pu Division of Hematology & Oncology
- YU-CHUAN LU Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
- CHUNG-HSIN CHEN Division of Hematology & Oncology
- JHE-CYUAN GUO Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Muscle- Invasive Bladder Cancer
Objectives
Primary Objectives
To compare the pCR rate of neoadjuvant nivolumab/BMS-986205 + GC to neoadjuvant GC alone in
all randomized participants.
To compare EFS of neoadjuvant nivolumab/BMS-986205 +GC followed by continued nivolumab/BMS-986205 after
RC versus SOC GC followed by RC in all randomized participants.
To compare the pCR rate of neoadjuvant nivolumab + GC to neoadjuvant GC alone in all randomized participants.
To compare EFS of neoadjuvant nivolumab + GC followed by continued nivolumab after RC versus neoadjuvant SOC
GC followed by RC in all randomized participants.
Test Drug
BMS-986205
Active Ingredient
BMS-986205
Dosage Form
film coated tablet
Dosage
50, 100
Endpoints
Primary Outcome Measures :
Pathological Complete Response (pCR) rate, in all randomized participants [ Time Frame: Approx. 39 months ]
Comparison of Arm B to Arm A; and Comparison of Arm C to Arm A
Event-Free Survival (EFS), in all randomized participants [ Time Frame: Approx. 57 months ]
Comparison of Arm B to Arm A; and Comparison of Arm C to Arm A;
Secondary Outcome Measures :
Overall Survival (OS) in all randomized participants [ Time Frame: Approx. 76 months ]
Comparison of Arm C vs Arm A; and Comparison of Arm B vs Arm A
Incidence of Adverse Events (AE) in all treated participants [ Time Frame: Approx. 76 months ]
Incidence of Serious Adverse Events (SAE) in all treated participants [ Time Frame: Approx. 76 months ]
Incidence of Laboratory abnormalities in all treated participants [ Time Frame: Approx. 76 months ]
Incidence of death in all treated participants [ Time Frame: Approx. 76 months ]
Pathological Complete Response (pCR) rate, in all randomized participants [ Time Frame: Approx. 39 months ]
Comparison of Arm B v Arm C
Event Free Survival (EFS), in all randomized participants [ Time Frame: Approx. 57 months ]
Comparison of Arm B v Arm C
Pathological Complete Response (pCR) rate, in all randomized participants [ Time Frame: Approx. 39 months ]
Comparison of Arm B to Arm A; and Comparison of Arm C to Arm A
Event-Free Survival (EFS), in all randomized participants [ Time Frame: Approx. 57 months ]
Comparison of Arm B to Arm A; and Comparison of Arm C to Arm A;
Secondary Outcome Measures :
Overall Survival (OS) in all randomized participants [ Time Frame: Approx. 76 months ]
Comparison of Arm C vs Arm A; and Comparison of Arm B vs Arm A
Incidence of Adverse Events (AE) in all treated participants [ Time Frame: Approx. 76 months ]
Incidence of Serious Adverse Events (SAE) in all treated participants [ Time Frame: Approx. 76 months ]
Incidence of Laboratory abnormalities in all treated participants [ Time Frame: Approx. 76 months ]
Incidence of death in all treated participants [ Time Frame: Approx. 76 months ]
Pathological Complete Response (pCR) rate, in all randomized participants [ Time Frame: Approx. 39 months ]
Comparison of Arm B v Arm C
Event Free Survival (EFS), in all randomized participants [ Time Frame: Approx. 57 months ]
Comparison of Arm B v Arm C
Inclution Criteria
Inclusion 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
patient care.
b) Participants must be willing and able to comply with scheduled visits, treatment schedule,
laboratory testing, tumor biopsies, and other requirements of the study.
2) Type of Participant and Target Disease Characteristics
a) Participants with MIBC, clinical stage T2-T4a, N0 (<10 mm on CT or MRI), M0,
diagnosed at TURBT and confirmed by radiographic imaging. Variant histology is
acceptable if there is a predominant urothelial component.
b) Participant must be deemed eligible for RC by his/her oncologist and/or urologist, and must
agree to undergo RC after completion of neoadjuvant therapy.
c) Prior BCG or other intravesical treatment of NMIBC is permitted if completed at least
6 weeks prior to initiating study treatment.
d) ECOG Performance Status 0 or 1
e) Life expectancy ≥ 6 months
f) Documentation of PD-L1 status by immunohistochemistry (IHC) performed by the central
lab during the screening period; the results must be submitted to IRT prior to
randomization. Either a formalin-fixed, paraffin-embedded (FFPE) tissue block or
20 unstained tumor tissue sections [minimum of 15 slides acceptable], with an associated
pathology report, must be submitted for biomarker evaluation prior to treatment. The tumor
tissue sample may be fresh or archival ( 4 months old), and should be from the TURBT
or biopsy that made the diagnosis of MIBC. No systemic therapy (eg, adjuvant or
neoadjuvant chemotherapy) should be given after the sample was obtained. PD-L1 results
are not required prior to beginning treatment on the safety lead-in.
g) Re-enrollment: This study permits the re-enrollment of a participant that has discontinued
the study as a pre-treatment failure (ie, participant has not been randomized (or treated in the safety lead-in). If re-enrolled, the participant must be re-consented and
inclusion/exclusion criteria reassessed.
3) Age and Reproductive Status
a) Males and females, ages 18 years 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) WOCBP must agree to follow instructions for methods(s) of contraception for the duration
of any study drugs (including chemotherapy) and 5 months after the last dose of any study
drugs (including chemotherapy) (ie, 30 days [duration of ovulatory cycle] plus the time
required for nivolumab to undergo approximately five half-lives).
e) Males who are sexually active with WOCBP must agree to use a latex or synthetic condom
during sexual activity (see Appendix 4) for the duration of treatment with study treatment
plus 7 months after the last dose of the study treatment (ie, 90 days [duration of sperm
turnover] plus the time required for nivolumab to undergo approximately 5 half-lives). This
criterion applies to azoospermic males as well.
f) WOCBP who are continuously not heterosexually active are exempt from contraceptive
requirements. However they must still undergo pregnancy testing as described in these
sections.
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
patient care.
b) Participants must be willing and able to comply with scheduled visits, treatment schedule,
laboratory testing, tumor biopsies, and other requirements of the study.
2) Type of Participant and Target Disease Characteristics
a) Participants with MIBC, clinical stage T2-T4a, N0 (<10 mm on CT or MRI), M0,
diagnosed at TURBT and confirmed by radiographic imaging. Variant histology is
acceptable if there is a predominant urothelial component.
b) Participant must be deemed eligible for RC by his/her oncologist and/or urologist, and must
agree to undergo RC after completion of neoadjuvant therapy.
c) Prior BCG or other intravesical treatment of NMIBC is permitted if completed at least
6 weeks prior to initiating study treatment.
d) ECOG Performance Status 0 or 1
e) Life expectancy ≥ 6 months
f) Documentation of PD-L1 status by immunohistochemistry (IHC) performed by the central
lab during the screening period; the results must be submitted to IRT prior to
randomization. Either a formalin-fixed, paraffin-embedded (FFPE) tissue block or
20 unstained tumor tissue sections [minimum of 15 slides acceptable], with an associated
pathology report, must be submitted for biomarker evaluation prior to treatment. The tumor
tissue sample may be fresh or archival ( 4 months old), and should be from the TURBT
or biopsy that made the diagnosis of MIBC. No systemic therapy (eg, adjuvant or
neoadjuvant chemotherapy) should be given after the sample was obtained. PD-L1 results
are not required prior to beginning treatment on the safety lead-in.
g) Re-enrollment: This study permits the re-enrollment of a participant that has discontinued
the study as a pre-treatment failure (ie, participant has not been randomized (or treated in the safety lead-in). If re-enrolled, the participant must be re-consented and
inclusion/exclusion criteria reassessed.
3) Age and Reproductive Status
a) Males and females, ages 18 years 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) WOCBP must agree to follow instructions for methods(s) of contraception for the duration
of any study drugs (including chemotherapy) and 5 months after the last dose of any study
drugs (including chemotherapy) (ie, 30 days [duration of ovulatory cycle] plus the time
required for nivolumab to undergo approximately five half-lives).
e) Males who are sexually active with WOCBP must agree to use a latex or synthetic condom
during sexual activity (see Appendix 4) for the duration of treatment with study treatment
plus 7 months after the last dose of the study treatment (ie, 90 days [duration of sperm
turnover] plus the time required for nivolumab to undergo approximately 5 half-lives). This
criterion applies to azoospermic males as well.
f) WOCBP who are continuously not heterosexually active are exempt from contraceptive
requirements. However they must still undergo pregnancy testing as described in these
sections.
Exclusion Criteria
Exclusion Criteria
1) Target Disease Exceptions
a) Clinical evidence of pathologic LN (≥ 10 mm in short axis) or metastatic bladder cancer
2) Medical Conditions
a) Ineligible to receive cisplatin due to Grade 2 or higher peripheral neuropathy or
audiometric hearing loss, or calculated (Cockcroft-Gault formula) or measured (24-hour
urine) creatinine clearance (CrCl) < 50 mL/min
b) 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.
c) Participants with conditions known to interfere significantly with the absorption of oral
medication, as per investigator judgement.
d) 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.
e) Participants with uncontrolled adrenal insufficiency.
f) Unstable angina, New York Heart Association (NYHA) Grade II or greater congestive
heart failure, history of myocardial infarction or stroke within 6 months (Appendix 8).
g) Evidence of bleeding diathesis or coagulopathy. Therapeutic anticoagulation is permitted,
but participants must be on a stable dose.
h) Participants with a personal or family (ie, in a first-degree relative) history or presence of
cytochrome b5 reductase deficiency (previously called methemoglobin reductase
deficiency) or other diseases that puts them at risk of methemoglobinemia. All participants
will be screened for methemoglobin levels prior to randomization.
i) Participants with a history of G6PD deficiency or other congenital or autoimmune
hemolytic disorders. All participants will be screened for G6PD deficiency prior to
randomization.
j) Prior history of serotonin syndrome
k) Participants with active interstitial lung disease (ILD) or pneumonitis or with recent history
of ILD or pneumonitis requiring steroids (excluding radiation pneumonitis)
l) Known medical condition that, in the Investigator’s opinion, would increase the risk
associated with study participation or study drug administration or interfere with the
interpretation of safety results
m) 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, prostate cancer with evidence of undetectable Prostate Specific Antigen (PSA), or
carcinoma in situ of the prostate, cervix, or breast
n) Major surgical procedure within 14 days prior to initiating study treatment or anticipation
of the need for a major surgical procedure (other than RC) during the course of the study
3) Prior/Concomitant Therapy
a) Prior treatment of bladder cancer (including MIBC) with systemic chemotherapy,
immunotherapy, radiation therapy, or surgery for bladder cancer other than TURBT or biopsies. Prior intravesical BCG or chemotherapy is permitted if completed at least 6 weeks
before initiating study treatment.
b) Participants may not have received live/attenuated vaccines within 30 days of first
treatment.
c) Use of an investigational agent within 4 weeks of the start of study treatment.
d) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or
any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint
pathways.
e) Treatment with botanical preparations (eg, herbal supplements or traditional Chinese
medicines) intended for general health support or to treat the disease under study within
2 weeks prior to randomization. Refer to Section 7.7.1 for additional notes.
4) Physical and Laboratory Test Findings
a) WBC < 2000/L
b) Neutrophils < 1500/L
c) Platelets < 100 103
/L
d) Hemoglobin < 9.0 g/dL (transfusion to achieve this level is not permitted within 1 week of
this laboratory assessment)
e) CrCl < 50 mL/min (measured or calculated 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]
f) AST or ALT > 3.0 ULN
g) Total bilirubin > 1.5 ULN (except participants with Gilbert Syndrome who must have a
total bilirubin level of < 3.0 ULN)
h) Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of
virus, eg, Hepatitis B surface antigen (HBsAg) positive, or Hepatitis C antibody (antiHCV) positive (except if HCV RNA negative)
i) 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.
j) Quantitative or qualitative G6PD assay results suggesting underlying G6PD deficiency
(refer to current investigator brochure)
k) Blood methemoglobin > ULN, assessed in an arterial or venous blood sample
l) Positive pregnancy test at enrollment or prior to administration of study medication
5) Allergies and Adverse Drug Reaction
a) History or presence of hypersensitivity or idiosyncratic reaction to methylene blue
b) History of allergy or hypersensitivity to any study treatment components
6) Other Exclusion Criteria
a) Prisoners or participants who are involuntarily incarcerated. (Note: under specific
circumstances a person who has been imprisoned may be included 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
1) Target Disease Exceptions
a) Clinical evidence of pathologic LN (≥ 10 mm in short axis) or metastatic bladder cancer
2) Medical Conditions
a) Ineligible to receive cisplatin due to Grade 2 or higher peripheral neuropathy or
audiometric hearing loss, or calculated (Cockcroft-Gault formula) or measured (24-hour
urine) creatinine clearance (CrCl) < 50 mL/min
b) 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.
c) Participants with conditions known to interfere significantly with the absorption of oral
medication, as per investigator judgement.
d) 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.
e) Participants with uncontrolled adrenal insufficiency.
f) Unstable angina, New York Heart Association (NYHA) Grade II or greater congestive
heart failure, history of myocardial infarction or stroke within 6 months (Appendix 8).
g) Evidence of bleeding diathesis or coagulopathy. Therapeutic anticoagulation is permitted,
but participants must be on a stable dose.
h) Participants with a personal or family (ie, in a first-degree relative) history or presence of
cytochrome b5 reductase deficiency (previously called methemoglobin reductase
deficiency) or other diseases that puts them at risk of methemoglobinemia. All participants
will be screened for methemoglobin levels prior to randomization.
i) Participants with a history of G6PD deficiency or other congenital or autoimmune
hemolytic disorders. All participants will be screened for G6PD deficiency prior to
randomization.
j) Prior history of serotonin syndrome
k) Participants with active interstitial lung disease (ILD) or pneumonitis or with recent history
of ILD or pneumonitis requiring steroids (excluding radiation pneumonitis)
l) Known medical condition that, in the Investigator’s opinion, would increase the risk
associated with study participation or study drug administration or interfere with the
interpretation of safety results
m) 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, prostate cancer with evidence of undetectable Prostate Specific Antigen (PSA), or
carcinoma in situ of the prostate, cervix, or breast
n) Major surgical procedure within 14 days prior to initiating study treatment or anticipation
of the need for a major surgical procedure (other than RC) during the course of the study
3) Prior/Concomitant Therapy
a) Prior treatment of bladder cancer (including MIBC) with systemic chemotherapy,
immunotherapy, radiation therapy, or surgery for bladder cancer other than TURBT or biopsies. Prior intravesical BCG or chemotherapy is permitted if completed at least 6 weeks
before initiating study treatment.
b) Participants may not have received live/attenuated vaccines within 30 days of first
treatment.
c) Use of an investigational agent within 4 weeks of the start of study treatment.
d) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or
any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint
pathways.
e) Treatment with botanical preparations (eg, herbal supplements or traditional Chinese
medicines) intended for general health support or to treat the disease under study within
2 weeks prior to randomization. Refer to Section 7.7.1 for additional notes.
4) Physical and Laboratory Test Findings
a) WBC < 2000/L
b) Neutrophils < 1500/L
c) Platelets < 100 103
/L
d) Hemoglobin < 9.0 g/dL (transfusion to achieve this level is not permitted within 1 week of
this laboratory assessment)
e) CrCl < 50 mL/min (measured or calculated 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]
f) AST or ALT > 3.0 ULN
g) Total bilirubin > 1.5 ULN (except participants with Gilbert Syndrome who must have a
total bilirubin level of < 3.0 ULN)
h) Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of
virus, eg, Hepatitis B surface antigen (HBsAg) positive, or Hepatitis C antibody (antiHCV) positive (except if HCV RNA negative)
i) 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.
j) Quantitative or qualitative G6PD assay results suggesting underlying G6PD deficiency
(refer to current investigator brochure)
k) Blood methemoglobin > ULN, assessed in an arterial or venous blood sample
l) Positive pregnancy test at enrollment or prior to administration of study medication
5) Allergies and Adverse Drug Reaction
a) History or presence of hypersensitivity or idiosyncratic reaction to methylene blue
b) History of allergy or hypersensitivity to any study treatment components
6) Other Exclusion Criteria
a) Prisoners or participants who are involuntarily incarcerated. (Note: under specific
circumstances a person who has been imprisoned may be included 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
The Estimated Number of Participants
-
Taiwan
21 participants
-
Global
1200 participants
