Clinical Trials List
Protocol NumberWO30070
NCT Number(ClinicalTrials.gov Identfier)NCT02807636
Completed
2016-06-01 - 2024-06-28
Phase III
Terminated6
ICD-10C66.2
Malignant neoplasm of left ureter
ICD-10C67
Malignant neoplasm of bladder
A PHASE III, MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND STUDY OF ATEZOLIZUMAB (ANTI−PD-L1 ANTIBODY) IN COMBINATION WITH GEMCITABINE/CARBOPLATIN VERSUS GEMCITABINE/CARBOPLATIN ALONE IN PATIENTS WITH UNTREATED LOCALLY ADVANCED OR METASTATIC UROTHELIAL CARCINOMA WHO ARE INELIGIBLE FOR CISPLATIN-BASED THERAPY
-
Trial Applicant
-
Sponsor
Hoffmann-La Roche
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Wu-Chou Su Division of General Internal Medicine
- Sin-Syue Li Division of General Internal Medicine
- Yu-Min Yeh Division of General Internal Medicine
- Shang-Yin Wu Division of General Internal Medicine
- Wei-Pang Chung Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- 劉建廷 Division of Hematology & Oncology
- 陳彥豪 Division of Hematology & Oncology
- 陳彥仰 Division of Hematology & Oncology
- Tai-Jan Chiu Division of Hematology & Oncology
- Shau-Hsuan Li Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Che-Hung Lin Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Shian-Shiang Wang Division of Urology
- Cheng-Che Chen Division of Urology
- 裘坤元 Division of Urology
- 洪啟峰 Division of Urology
- Cheng-Kuang Yang Division of Urology
- 熊小澐 Division of Radiology
- Chuan-Shu Chen Division of Urology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Linkou Chang Gung Medical Foundation
Taiwan National PI
莊正鏗
Co-Principal Investigator
- See-Tong Pang Division of Hematology & Oncology
- 劉忠一 Division of Hematology & Oncology
- Po-Jung Su Division of Hematology & Oncology
- Yung-Chia Kao Division of Hematology & Oncology
- 張英勛 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
1 Terminated
Audit
None
Co-Principal Investigator
- Yeong-Shiau Pu Division of Urology
- - - Division of Urology
- CHUNG-HSIN CHEN Division of Urology
- JHE-CYUAN GUO Division of Hematology & Oncology
- - - Division of Urology
- Ying-Chun Shen Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
LOCALLY ADVANCED OR METASTATIC UROTHELIAL CARCINOMA
Objectives
This is a Phase III, multicenter, randomized, placebo-controlled, double-blind study
designed to evaluate the efficacy of atezolizumab in combination with
gemcitabine/carboplatin versus placebo in combination with gemcitabine/carboplatin in
patients with locally advanced or metastatic UC, who have not received prior systemic
therapy and who are ineligible to receive cisplatin-based therapy.
Test Drug
TECENTRIQ (Atezolizumab)
Active Ingredient
Atezolizumab
Dosage Form
Injection
Dosage
1200mg/20ml
Endpoints
Primary Outcome Measures :
1. Progression-Free Survival (PFS) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in Participants Treated with Atezolizumab Combination Therapy Compared With Placebo Arm
2. Overall Survival (OS)
3. Percentage of Participants with Adverse Events (AEs) Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Secondary Outcome Measures :
1. Percentage of Participants with Best Overall Response of Complete Response (CR) or Partial Response (PR) Assessed by Investigator Using RECIST v1.1
2. Duration of response (DOR) Assessed by Investigator Using RECIST v1.1
3. IRF-PFS as determined by blinded independent central review using RECIST v1.1
4. Percentage of Participants Who Were Alive at Year 1
5. Percentage of Participants Who Were Alive and Progression Free at Year 1 Using RECIST v1.1
6. Median Time to Deterioration in Global Health Status as Measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score
7. Median Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score
8. Maximum Atezolizumab Serum Concentration
9. Minimum Atezolizumab Serum Concentration
10. Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs)
11. Investigator-Assessed Progression-Free Survival (INV-PFS) Assessed by Investigator Using RECIST v1.1 in Participants Treated with Atezolizumab Montotherapy Compared With Placebo Arm
1. Progression-Free Survival (PFS) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in Participants Treated with Atezolizumab Combination Therapy Compared With Placebo Arm
2. Overall Survival (OS)
3. Percentage of Participants with Adverse Events (AEs) Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Secondary Outcome Measures :
1. Percentage of Participants with Best Overall Response of Complete Response (CR) or Partial Response (PR) Assessed by Investigator Using RECIST v1.1
2. Duration of response (DOR) Assessed by Investigator Using RECIST v1.1
3. IRF-PFS as determined by blinded independent central review using RECIST v1.1
4. Percentage of Participants Who Were Alive at Year 1
5. Percentage of Participants Who Were Alive and Progression Free at Year 1 Using RECIST v1.1
6. Median Time to Deterioration in Global Health Status as Measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score
7. Median Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score
8. Maximum Atezolizumab Serum Concentration
9. Minimum Atezolizumab Serum Concentration
10. Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs)
11. Investigator-Assessed Progression-Free Survival (INV-PFS) Assessed by Investigator Using RECIST v1.1 in Participants Treated with Atezolizumab Montotherapy Compared With Placebo Arm
Inclution Criteria
Inclusion Criteria
Patients must meet the following criteria for study entry:
• Signed Informed Consent Form
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Able to comply with the study protocol, in the investigator’s judgment
• Histologically documented, locally advanced (T4b, any N; or any T, N 2−3) or metastatic
urothelial carcinoma (mUC) (M1, Stage IV) (also termed TCC or UCC of the urinary tract;
including renal pelvis, ureters, urinary bladder, and urethra)
Patients with mixed histologies are required to have a dominant transitional cell pattern.
Locally advanced bladder cancer must be inoperable on the basis of involvement of
pelvic sidewall or adjacent viscera (clinical Stage T4b) or bulky nodal metastasis
(N2−N3).
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin
blocks (blocks preferred) or at least 15 unstained slides, with an associated pathology
report, for central testing and determined to be evaluable for tumor PD-L1 expression prior
to study enrollment; patients who have fewer than 15 unstained slides available at baseline
(but no fewer than 10) may be eligible following discussion with the Medical Monitor.
Tumor tissue should be of good quality based on total and viable tumor content.
Fine-needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, and
lavage samples are not acceptable. For core-needle biopsy specimens, at least three
cores should be submitted for evaluation.
Transurethral Resection of Bladder Tumor (TURBT) specimens must contain a muscle
invasive component (i.e., T2 or greater) of the bladder tumor as verified by local
pathology review. If the TURBT specimens do not contain a muscle invasive
component, then specimens obtained at the time of cystectomy/nephroureterectomy or
metastatic spread (i.e., sample from a metastatic lesion) will be required prior to
randomization. An archival specimen, if available, should also be submitted.
Patients who do not have tissue specimens that meet eligibility requirements may
undergo a biopsy during the screening period. Acceptable samples include core needle
biopsies for deep tumor tissue (minimum three cores) or excisional, incisional, punch, or
forceps biopsies for cutaneous, subcutaneous, or mucosal lesions.
Tumor tissue from bone metastases is not evaluable for PD-L1 expression and is
therefore not acceptable.
Patients who have additional tissue samples from procedures performed at different
times during the course of their urothelial carcinoma may also submit these samples for
central testing. Tissue samples that are obtained at multiple times for individual
patients may contribute to an improved understanding of the dynamics of PD-L1
expression and relationship with intervening anti-cancer therapy. In situations where
multiple specimens were received from different sites or at different times, the highest
score will be used for stratification and for subsequent analyses.
• No prior chemotherapy for inoperable locally advanced or mUC
For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation
for urothelial carcinoma, a treatment-free interval > 12 months between the last
treatment administration and the date of recurrence is required in order to be
considered treatment naive in the metastatic setting.
Prior local intravesical chemotherapy or immunotherapy is allowed if completed at least
4 weeks prior to the initiation of study treatment.
• Ineligible (“unfit”) for cisplatin-based chemotherapy as defined by any one of the following
criteria:
Impaired renal function (glomerular filtration rate [GFR] > 30 but < 60 mL/min); GFR
should be assessed by direct measurement (i.e., creatinine clearance or
ethyldediaminetetra-acetate) or, if not available, by calculation from serum/plasma
creatinine (Cockcroft-Gault formula)
CTCAE v4.0 Grade ≥ 2 audiometric hearing loss of 25 dB at two contiguous frequencies
CTCAE v4.0 Grade ≥ 2 peripheral neuropathy (i.e., sensory alteration or paresthesias,
including tingling)
ECOG performance status of 2
• Measurable disease, as defined by RECIST v1.1
Previously irradiated lesions should not be counted as target lesions unless there has
been demonstrated progression in the lesion since radiotherapy and no other lesions
are available for selection as target lesions.
• Adequate hematologic and end-organ function, defined by the following laboratory results
obtained within 28 days prior to the first study treatment:
ANC ≥ 1500 cells/μL (without granulocyte colony-stimulating factor support within
2 weeks prior to Cycle 1, Day 1)
WBC counts > 2500/μL
Lymphocyte count ≥ 300/μL
Platelet count ≥ 100,000/μL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
Hemoglobin ≥ 9.0 g/dL
Patients may be transfused to meet this criterion.
Patients with a solitary kidney or chronic kidney disease with low erythropoietin
production may use erythropoietin-stimulating agents.
AST, ALT, and alkaline phosphatase ≤ 2.5 × the upper limit of normal (ULN), with the
following exceptions:
Patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN
Patients with documented liver or bone metastases: alkaline phosphatase
≤ 5 × ULN
Serum bilirubin ≤ 1.5 × ULN
Patients with known Gilbert disease who have serum bilirubin level ≤ 3 × ULN may
be enrolled.
PTT ≤ 1.5 × ULN
PT ≤ 1.5 × ULN or INR < 1.7
This applies only to patients who are not receiving therapeutic anticoagulation;
patients receiving therapeutic anticoagulation should be on a stable dose.
Calculated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula)
Serum calcium ≤ 12 mg/dL
For patients with serum albumin < 4.0 g/dL, corrected serum calcium must
be ≤ ULN
• For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1%
per year during the treatment period and for at least 6 months after the last dose of
carboplatin or gemcitabine or for 90 days after the last dose of atezolizumab
A woman is considered to be of childbearing potential if she is postmenarcheal, has
not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no
identified cause other than menopause), and has not undergone surgical sterilization
(removal of ovaries and/or uterus).
Examples of contraceptive methods with a failure rate of < 1% per year
include bilateral tubal ligation, male sterilization, established and proper use
of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine
devices, and copper intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the duration of
the clinical study and the preferred and usual lifestyle of the patient. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
withdrawal are not acceptable methods of contraception.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures and agreement to refrain from donating sperm, as defined below:
With female partners of childbearing potential, men must remain abstinent or use a
condom plus an additional contraceptive method that together result in a failure rate
of < 1% per year during the treatment period and for at least 6 months after the last
dose of gemcitabine and/or carboplatin. Men must refrain from donating sperm during
this same period.
The reliability of sexual abstinence should be evaluated in relation to the duration of
the clinical study and the preferred and usual lifestyle of the patient. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
withdrawal are not acceptable methods of contraception.
Patients must meet the following criteria for study entry:
• Signed Informed Consent Form
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Able to comply with the study protocol, in the investigator’s judgment
• Histologically documented, locally advanced (T4b, any N; or any T, N 2−3) or metastatic
urothelial carcinoma (mUC) (M1, Stage IV) (also termed TCC or UCC of the urinary tract;
including renal pelvis, ureters, urinary bladder, and urethra)
Patients with mixed histologies are required to have a dominant transitional cell pattern.
Locally advanced bladder cancer must be inoperable on the basis of involvement of
pelvic sidewall or adjacent viscera (clinical Stage T4b) or bulky nodal metastasis
(N2−N3).
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin
blocks (blocks preferred) or at least 15 unstained slides, with an associated pathology
report, for central testing and determined to be evaluable for tumor PD-L1 expression prior
to study enrollment; patients who have fewer than 15 unstained slides available at baseline
(but no fewer than 10) may be eligible following discussion with the Medical Monitor.
Tumor tissue should be of good quality based on total and viable tumor content.
Fine-needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, and
lavage samples are not acceptable. For core-needle biopsy specimens, at least three
cores should be submitted for evaluation.
Transurethral Resection of Bladder Tumor (TURBT) specimens must contain a muscle
invasive component (i.e., T2 or greater) of the bladder tumor as verified by local
pathology review. If the TURBT specimens do not contain a muscle invasive
component, then specimens obtained at the time of cystectomy/nephroureterectomy or
metastatic spread (i.e., sample from a metastatic lesion) will be required prior to
randomization. An archival specimen, if available, should also be submitted.
Patients who do not have tissue specimens that meet eligibility requirements may
undergo a biopsy during the screening period. Acceptable samples include core needle
biopsies for deep tumor tissue (minimum three cores) or excisional, incisional, punch, or
forceps biopsies for cutaneous, subcutaneous, or mucosal lesions.
Tumor tissue from bone metastases is not evaluable for PD-L1 expression and is
therefore not acceptable.
Patients who have additional tissue samples from procedures performed at different
times during the course of their urothelial carcinoma may also submit these samples for
central testing. Tissue samples that are obtained at multiple times for individual
patients may contribute to an improved understanding of the dynamics of PD-L1
expression and relationship with intervening anti-cancer therapy. In situations where
multiple specimens were received from different sites or at different times, the highest
score will be used for stratification and for subsequent analyses.
• No prior chemotherapy for inoperable locally advanced or mUC
For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation
for urothelial carcinoma, a treatment-free interval > 12 months between the last
treatment administration and the date of recurrence is required in order to be
considered treatment naive in the metastatic setting.
Prior local intravesical chemotherapy or immunotherapy is allowed if completed at least
4 weeks prior to the initiation of study treatment.
• Ineligible (“unfit”) for cisplatin-based chemotherapy as defined by any one of the following
criteria:
Impaired renal function (glomerular filtration rate [GFR] > 30 but < 60 mL/min); GFR
should be assessed by direct measurement (i.e., creatinine clearance or
ethyldediaminetetra-acetate) or, if not available, by calculation from serum/plasma
creatinine (Cockcroft-Gault formula)
CTCAE v4.0 Grade ≥ 2 audiometric hearing loss of 25 dB at two contiguous frequencies
CTCAE v4.0 Grade ≥ 2 peripheral neuropathy (i.e., sensory alteration or paresthesias,
including tingling)
ECOG performance status of 2
• Measurable disease, as defined by RECIST v1.1
Previously irradiated lesions should not be counted as target lesions unless there has
been demonstrated progression in the lesion since radiotherapy and no other lesions
are available for selection as target lesions.
• Adequate hematologic and end-organ function, defined by the following laboratory results
obtained within 28 days prior to the first study treatment:
ANC ≥ 1500 cells/μL (without granulocyte colony-stimulating factor support within
2 weeks prior to Cycle 1, Day 1)
WBC counts > 2500/μL
Lymphocyte count ≥ 300/μL
Platelet count ≥ 100,000/μL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
Hemoglobin ≥ 9.0 g/dL
Patients may be transfused to meet this criterion.
Patients with a solitary kidney or chronic kidney disease with low erythropoietin
production may use erythropoietin-stimulating agents.
AST, ALT, and alkaline phosphatase ≤ 2.5 × the upper limit of normal (ULN), with the
following exceptions:
Patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN
Patients with documented liver or bone metastases: alkaline phosphatase
≤ 5 × ULN
Serum bilirubin ≤ 1.5 × ULN
Patients with known Gilbert disease who have serum bilirubin level ≤ 3 × ULN may
be enrolled.
PTT ≤ 1.5 × ULN
PT ≤ 1.5 × ULN or INR < 1.7
This applies only to patients who are not receiving therapeutic anticoagulation;
patients receiving therapeutic anticoagulation should be on a stable dose.
Calculated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula)
Serum calcium ≤ 12 mg/dL
For patients with serum albumin < 4.0 g/dL, corrected serum calcium must
be ≤ ULN
• For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1%
per year during the treatment period and for at least 6 months after the last dose of
carboplatin or gemcitabine or for 90 days after the last dose of atezolizumab
A woman is considered to be of childbearing potential if she is postmenarcheal, has
not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no
identified cause other than menopause), and has not undergone surgical sterilization
(removal of ovaries and/or uterus).
Examples of contraceptive methods with a failure rate of < 1% per year
include bilateral tubal ligation, male sterilization, established and proper use
of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine
devices, and copper intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the duration of
the clinical study and the preferred and usual lifestyle of the patient. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
withdrawal are not acceptable methods of contraception.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures and agreement to refrain from donating sperm, as defined below:
With female partners of childbearing potential, men must remain abstinent or use a
condom plus an additional contraceptive method that together result in a failure rate
of < 1% per year during the treatment period and for at least 6 months after the last
dose of gemcitabine and/or carboplatin. Men must refrain from donating sperm during
this same period.
The reliability of sexual abstinence should be evaluated in relation to the duration of
the clinical study and the preferred and usual lifestyle of the patient. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
withdrawal are not acceptable methods of contraception.
Exclusion Criteria
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:
Cancer-Specific Exclusions
• Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within
3 weeks prior to initiation of study treatment; the following exceptions are allowed:
Palliative radiotherapy for bone metastases or soft tissue lesions should be
completed > 7 days prior to baseline imaging.
Hormone-replacement therapy or oral contraceptives
• Treatment with any other investigational agent or participation in another clinical study with
therapeutic intent within 28 days prior to enrollment
• Active or untreated CNS metastases as determined by computed tomography or magnetic
resonance imaging evaluation during screening and prior radiographic assessments
Patients with treated asymptomatic CNS metastases are eligible, provided they meet all
of the following criteria:
Evaluable or measurable disease outside the CNS
No metastases to midbrain, pons, medulla, or within 10 mm of the optic apparatus
(optic nerves and chiasm)
No history of intracranial or spinal cord hemorrhage
No ongoing requirement for corticosteroid as therapy for CNS disease;
anti-convulsants at a stable dose are allowed
No evidence of significant vasogenic edema
No stereotactic radiation, whole-brain radiation or neurosurgical resection within
4 weeks prior to Cycle 1, Day 1
Radiographic demonstration of interim stability (i.e., no progression) between the
completion of CNS-directed therapy and the screening radiographic study
Screening CNS radiographic study ≥ 4 weeks since completion of radiotherapy or
surgical resection and ≥ 2 weeks since discontinuation of corticosteroids
• Leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage
procedures (once monthly or more frequently)
Patients with indwelling catheters (e.g., PleurX) are allowed.
• Uncontrolled tumor-related pain
Patients who require pain medication must be on a stable regimen at study entry.
Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or
metastases causing nerve impingement) should be treated prior to enrollment.
Asymptomatic metastatic lesions whose further growth would likely cause functional
deficits or intractable pain (e.g., epidural metastasis that is not presently associated
with spinal cord compression) should be considered for loco-regional therapy if
appropriate prior to enrollment.
• Uncontrolled hypercalcemia defined as any one or more of the following criteria:
> 1.5 mmol/L ionized calcium
Serum calcium > 12 mg/dL
Corrected serum calcium > ULN (if serum albumin < 4.0 g/dL)
Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or
denosumab
Patients who are receiving bisphosphonate therapy or denosumab specifically to
prevent skeletal events and who do not have a history of clinically significant
hypercalcemia are eligible.
• Malignancies other than urothelial carcinoma within 5 years prior to Cycle 1, Day 1
Patients with localized low-risk prostate cancer (defined as Stage ≤ pT2b, Gleason
score ≤ 7, and prostate-specific antigen (PSA) at prostate cancer diagnosis ≤ 20 ng/mL)
treated with curative intent and without PSA recurrence are eligible.
Patients with pre-existing low-risk prostate cancer (defined as Stage cT1/T2a, Gleason
score ≤ 6 and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active
surveillance are eligible.
Patients with malignancies of a negligible risk of metastasis or death (e.g., risk of
metastasis or death < 5% at 5 years) are eligible provided they meet all of the following
criteria:
Malignancy treated with expected curative intent (e.g., adequately treated
carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal
carcinoma in situ treated surgically with curative intent)
No evidence of recurrence or metastasis by follow-up imaging and any
disease-specific tumor markers
General Medical Exclusions
• Life expectancy of < 12 weeks
• Pregnant or lactating, or intending to become pregnant during the study
Women of childbearing potential must have a negative serum pregnancy test result
within 7 days prior to initiation of study drug.
• Serum albumin < 2.5 g/dL
Exclusion Criteria Related to Atezolizumab
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or
humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary
cells or any component of the atezolizumab formulation
• History of autoimmune disease including but not limited to myasthenia gravis, myositis,
autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory
bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s
granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis,
or glomerulonephritis
Patients with a history of autoimmune-related hypothyroidism on a stable dose of
thyroid-replacement hormone may be eligible for this study.
Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be
eligible for this study.
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic
manifestations only (e.g., patients with psoriatic arthritis) are permitted provided that
they meet the following conditions:
Rash must cover less than 10% of body surface area (BSA)
Disease is well controlled at baseline and only requiring low potency topical
steroids
No acute exacerbations of underlying condition within the last 12 months (not
requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate, retinoids,
biologic agents, oral calcineurin inhibitors, high potency or oral steroids)
• Patients with prior allogeneic stem cell or solid organ transplantation
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis,
organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or
evidence of active pneumonitis on screening chest computed tomography (CT) scan
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Significant cardiovascular disease, such as New York Heart Association cardiac disease
(Class III or greater), myocardial infarction within 3 months prior to randomization, unstable
arrhythmias, or unstable angina
• Known left ventricular ejection fraction (LVEF) < 40%
Patients with known coronary artery disease, congestive heart failure not meeting the
above criteria, or LVEF 40%−50% must be on a stable medical regimen that is
optimized in the opinion of the treating physician, in consultation with a cardiologist if
appropriate. Patients with a history of clinically significant cardiac disease (including
anatomic abnormality, coronary disease, congestive heart failure, abnormal LVEF,
arrhythmia, or abnormal ECG) will be required to undergo a screening echocardiogram.
• Positive test for HIV
• Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at
screening) or hepatitis C
Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined
as having a negative HBsAg test and a positive antibody to hepatitis B core antigen
[anti-HBc] antibody test) are eligible. A negative HBV DNA test must be obtained in
these patients prior to Cycle 1, Day 1.
Patients who test positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction is negative for HCV RNA.
• Active tuberculosis
• Severe infections within 4 weeks prior to randomization including but not limited to
hospitalization for complications of infection, bacteremia, or severe pneumonia
• Therapeutic oral or IV antibiotics within 2 weeks prior to randomization
Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
infection or chronic obstructive pulmonary disease or for dental extraction) are eligible.
• Major surgical procedure within 4 weeks prior to randomization or anticipation of need for a
major surgical procedure during the course of the study other than for diagnosis.
• Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
Influenza vaccination should be given during influenza season only (approximately
October through May in the Northern Hemisphere and approximately April through
September in the Southern Hemisphere).
Patients must agree not to receive live, attenuated influenza vaccine within 28 days
prior to randomization, during treatment, or within 90 days after the last dose of
atezolizumab.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that contraindicates
the use of an investigational drug or that may affect the interpretation of the results or
render the patient at high risk from treatment complications
• Prior treatment with CD137 agonists, anti-CTLA-4, anti−programmed death-1 (PD-1), or
anti−PD-L1 therapeutic antibody or pathway-targeting agents
• Treatment with systemic immunostimulatory agents (including but not limited to interferons
or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to
Cycle 1, Day 1.
• Treatment with systemic corticosteroids or other systemic immunosuppressive medications
(including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine,
methotrexate, thalidomide, and anti−tumor necrosis factor [TNF] agents) within 2 weeks
prior to to Cycle 1, Day 1 or anticipated requirement for systemic immunosuppressive
medications during the study
Patients who have received acute, low-dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in
the study after discussion with and approval by the Medical Monitor.
The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids
(i.e., for adrenal insufficiency), and mineralocorticoids (e.g., fludrocortisone) is allowed.
Patients who meet any of the following criteria will be excluded from study entry:
Cancer-Specific Exclusions
• Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within
3 weeks prior to initiation of study treatment; the following exceptions are allowed:
Palliative radiotherapy for bone metastases or soft tissue lesions should be
completed > 7 days prior to baseline imaging.
Hormone-replacement therapy or oral contraceptives
• Treatment with any other investigational agent or participation in another clinical study with
therapeutic intent within 28 days prior to enrollment
• Active or untreated CNS metastases as determined by computed tomography or magnetic
resonance imaging evaluation during screening and prior radiographic assessments
Patients with treated asymptomatic CNS metastases are eligible, provided they meet all
of the following criteria:
Evaluable or measurable disease outside the CNS
No metastases to midbrain, pons, medulla, or within 10 mm of the optic apparatus
(optic nerves and chiasm)
No history of intracranial or spinal cord hemorrhage
No ongoing requirement for corticosteroid as therapy for CNS disease;
anti-convulsants at a stable dose are allowed
No evidence of significant vasogenic edema
No stereotactic radiation, whole-brain radiation or neurosurgical resection within
4 weeks prior to Cycle 1, Day 1
Radiographic demonstration of interim stability (i.e., no progression) between the
completion of CNS-directed therapy and the screening radiographic study
Screening CNS radiographic study ≥ 4 weeks since completion of radiotherapy or
surgical resection and ≥ 2 weeks since discontinuation of corticosteroids
• Leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage
procedures (once monthly or more frequently)
Patients with indwelling catheters (e.g., PleurX) are allowed.
• Uncontrolled tumor-related pain
Patients who require pain medication must be on a stable regimen at study entry.
Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or
metastases causing nerve impingement) should be treated prior to enrollment.
Asymptomatic metastatic lesions whose further growth would likely cause functional
deficits or intractable pain (e.g., epidural metastasis that is not presently associated
with spinal cord compression) should be considered for loco-regional therapy if
appropriate prior to enrollment.
• Uncontrolled hypercalcemia defined as any one or more of the following criteria:
> 1.5 mmol/L ionized calcium
Serum calcium > 12 mg/dL
Corrected serum calcium > ULN (if serum albumin < 4.0 g/dL)
Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or
denosumab
Patients who are receiving bisphosphonate therapy or denosumab specifically to
prevent skeletal events and who do not have a history of clinically significant
hypercalcemia are eligible.
• Malignancies other than urothelial carcinoma within 5 years prior to Cycle 1, Day 1
Patients with localized low-risk prostate cancer (defined as Stage ≤ pT2b, Gleason
score ≤ 7, and prostate-specific antigen (PSA) at prostate cancer diagnosis ≤ 20 ng/mL)
treated with curative intent and without PSA recurrence are eligible.
Patients with pre-existing low-risk prostate cancer (defined as Stage cT1/T2a, Gleason
score ≤ 6 and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active
surveillance are eligible.
Patients with malignancies of a negligible risk of metastasis or death (e.g., risk of
metastasis or death < 5% at 5 years) are eligible provided they meet all of the following
criteria:
Malignancy treated with expected curative intent (e.g., adequately treated
carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal
carcinoma in situ treated surgically with curative intent)
No evidence of recurrence or metastasis by follow-up imaging and any
disease-specific tumor markers
General Medical Exclusions
• Life expectancy of < 12 weeks
• Pregnant or lactating, or intending to become pregnant during the study
Women of childbearing potential must have a negative serum pregnancy test result
within 7 days prior to initiation of study drug.
• Serum albumin < 2.5 g/dL
Exclusion Criteria Related to Atezolizumab
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or
humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary
cells or any component of the atezolizumab formulation
• History of autoimmune disease including but not limited to myasthenia gravis, myositis,
autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory
bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s
granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis,
or glomerulonephritis
Patients with a history of autoimmune-related hypothyroidism on a stable dose of
thyroid-replacement hormone may be eligible for this study.
Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be
eligible for this study.
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic
manifestations only (e.g., patients with psoriatic arthritis) are permitted provided that
they meet the following conditions:
Rash must cover less than 10% of body surface area (BSA)
Disease is well controlled at baseline and only requiring low potency topical
steroids
No acute exacerbations of underlying condition within the last 12 months (not
requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate, retinoids,
biologic agents, oral calcineurin inhibitors, high potency or oral steroids)
• Patients with prior allogeneic stem cell or solid organ transplantation
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis,
organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or
evidence of active pneumonitis on screening chest computed tomography (CT) scan
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Significant cardiovascular disease, such as New York Heart Association cardiac disease
(Class III or greater), myocardial infarction within 3 months prior to randomization, unstable
arrhythmias, or unstable angina
• Known left ventricular ejection fraction (LVEF) < 40%
Patients with known coronary artery disease, congestive heart failure not meeting the
above criteria, or LVEF 40%−50% must be on a stable medical regimen that is
optimized in the opinion of the treating physician, in consultation with a cardiologist if
appropriate. Patients with a history of clinically significant cardiac disease (including
anatomic abnormality, coronary disease, congestive heart failure, abnormal LVEF,
arrhythmia, or abnormal ECG) will be required to undergo a screening echocardiogram.
• Positive test for HIV
• Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at
screening) or hepatitis C
Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined
as having a negative HBsAg test and a positive antibody to hepatitis B core antigen
[anti-HBc] antibody test) are eligible. A negative HBV DNA test must be obtained in
these patients prior to Cycle 1, Day 1.
Patients who test positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction is negative for HCV RNA.
• Active tuberculosis
• Severe infections within 4 weeks prior to randomization including but not limited to
hospitalization for complications of infection, bacteremia, or severe pneumonia
• Therapeutic oral or IV antibiotics within 2 weeks prior to randomization
Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
infection or chronic obstructive pulmonary disease or for dental extraction) are eligible.
• Major surgical procedure within 4 weeks prior to randomization or anticipation of need for a
major surgical procedure during the course of the study other than for diagnosis.
• Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
Influenza vaccination should be given during influenza season only (approximately
October through May in the Northern Hemisphere and approximately April through
September in the Southern Hemisphere).
Patients must agree not to receive live, attenuated influenza vaccine within 28 days
prior to randomization, during treatment, or within 90 days after the last dose of
atezolizumab.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that contraindicates
the use of an investigational drug or that may affect the interpretation of the results or
render the patient at high risk from treatment complications
• Prior treatment with CD137 agonists, anti-CTLA-4, anti−programmed death-1 (PD-1), or
anti−PD-L1 therapeutic antibody or pathway-targeting agents
• Treatment with systemic immunostimulatory agents (including but not limited to interferons
or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to
Cycle 1, Day 1.
• Treatment with systemic corticosteroids or other systemic immunosuppressive medications
(including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine,
methotrexate, thalidomide, and anti−tumor necrosis factor [TNF] agents) within 2 weeks
prior to to Cycle 1, Day 1 or anticipated requirement for systemic immunosuppressive
medications during the study
Patients who have received acute, low-dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in
the study after discussion with and approval by the Medical Monitor.
The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids
(i.e., for adrenal insufficiency), and mineralocorticoids (e.g., fludrocortisone) is allowed.
The Estimated Number of Participants
-
Taiwan
30 participants
-
Global
1200 participants
