Clinical Trials List
Protocol NumberWO29637
NCT Number(ClinicalTrials.gov Identfier)NCT02420821
2015-04-10 - 2019-06-30
Phase III
Terminated3
ICD-10C64
Malignant neoplasm of kidney, except renal pelvis
A PHASE III, OPEN-LABEL, RANDOMIZED STUDY OF MPDL3280A (AntiPD-L1 ANTIBODY) IN COMBINATION WITH BEVACIZUMAB VERSUS SUNITINIB IN PATIENTS WITH UNTREATED ADVANCED RENAL CELL CARCINOMA
-
Trial Applicant
-
Sponsor
Hoffmann-La Roche
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 林萬鈺 Division of Urology
- Chuan-Shu Chen Division of Urology
- Cheng-Che Chen Division of Urology
- Shian-Shiang Wang Division of Urology
- 熊小澐 Division of Urology
- 洪啟峰 Division of Urology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 張英勛 Division of General Surgery
- See-Tong Pang Division of General Surgery
- Wen-Cheng Chang Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
6 Terminated
Audit
None
Co-Principal Investigator
- - - Division of Urology
- Yeong-Shiau Pu Division of Urology
- Yu-Chieh Tsai Division of Hematology & Oncology
- CHUNG-HSIN CHEN Division of Urology
- - - Division of Urology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
UNTREATED ADVANCED RENAL CELL CARCINOMA
Objectives
Analyses of the following objectives will be performed in an intent-to-treat (ITT) fashion for the
population of patients with inoperable, locally advanced, or metastatic renal cell carcinoma
(RCC), unless otherwise indicated. Where specified, a comparison of the treatment arms will
be performed in different patient subpopulations according to tumor programmed death-ligand 1
(PD-L1) expression as evaluated by immunohistochemistry (IHC).
Efficacy Objectives
The primary efficacy objective of the study is to evaluate the efficacy of
MPDL3280Abevacizumab compared with sunitinib as measured by investigator-assessed
progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1
(RECIST v1.1).
Test Drug
Atezolizumab
Active Ingredient
Atezolizumab
Dosage Form
Injection
Dosage
1200mg/20ml
Endpoints
Efficacy Outcome Measures
The primary efficacy outcome measure is PFS, defined as the time from randomization to the
first occurrence of disease progression, as determined by the investigator from tumor
assessments based on RECIST v1.1,or death from any cause.
The secondary efficacy outcome measures for this study are as follows:
PFS based on IRC assessment of radiographic progression per RECIST v1.1
OS, defined as the time from randomization to death due to any cause
Time to deterioration in tiredness on the basis of Question 3 on the BFI
Change from baseline in the following scores:
Fatigue interference (Question 4 on BFI)
Symptom interference (from MDASI)
Diarrhea severity (from the MDASI)
Treatment side effects subscale (from the FKSI-19)
ORR, defined as the proportion of patients with an objective response (either complete
response or partial response, confirmation not required) as determined by investigator per
RECIST v1.1
DOR, defined as the time from the first documented response to documented disease
progression as determined by the investigator per RECIST v1.1 or death due to any cause,
whichever occurs first
ORR and DOR based on IRC assessment per RECIST v1.1
PFS, ORR, and DOR based on investigator assessment per modified RECIST criteria
PFS based on investigator assessment per RECIST v1.1 and OS in patients who have
detectable PD-L1 expression, which is defined as IC1/2/3
Safety Outcome Measures
The safety outcome measures for this study are as follows:
Incidence, nature, and severity of all adverse events, including Grade 3 laboratory
toxicities (grading per National Cancer Institute Common Terminology Criteria for Adverse
Events version 4.0; laboratory toxicities based on local laboratory assessments), during
first-line treatment
Incidence of ATA response to MPDL3280A and potential correlation with pharmacokinetics,
safety, and efficacy parameters
Pharmacokinetic Outcome Measures
The pharmacokinetic outcome measures for this study are as follows:
Maximum MPDL3280A serum concentration (Cmax) after infusion on Cycle 1, Day 1
Minimum MPDL3280A serum concentration (Cmin) prior to the infusion on Day 1 of Cycles 1,
2, 4, 8 and every eight cycles thereafter; Day 22 of Cycles 1, 2, and 4; and at study
termination
Bevacizumab Cmax after infusion on Day 1 of Cycles 1 and 2
Bevacizumab Cmin prior to the infusion on Day 1 of Cycles 1 and 2 and at study termination
The primary efficacy outcome measure is PFS, defined as the time from randomization to the
first occurrence of disease progression, as determined by the investigator from tumor
assessments based on RECIST v1.1,or death from any cause.
The secondary efficacy outcome measures for this study are as follows:
PFS based on IRC assessment of radiographic progression per RECIST v1.1
OS, defined as the time from randomization to death due to any cause
Time to deterioration in tiredness on the basis of Question 3 on the BFI
Change from baseline in the following scores:
Fatigue interference (Question 4 on BFI)
Symptom interference (from MDASI)
Diarrhea severity (from the MDASI)
Treatment side effects subscale (from the FKSI-19)
ORR, defined as the proportion of patients with an objective response (either complete
response or partial response, confirmation not required) as determined by investigator per
RECIST v1.1
DOR, defined as the time from the first documented response to documented disease
progression as determined by the investigator per RECIST v1.1 or death due to any cause,
whichever occurs first
ORR and DOR based on IRC assessment per RECIST v1.1
PFS, ORR, and DOR based on investigator assessment per modified RECIST criteria
PFS based on investigator assessment per RECIST v1.1 and OS in patients who have
detectable PD-L1 expression, which is defined as IC1/2/3
Safety Outcome Measures
The safety outcome measures for this study are as follows:
Incidence, nature, and severity of all adverse events, including Grade 3 laboratory
toxicities (grading per National Cancer Institute Common Terminology Criteria for Adverse
Events version 4.0; laboratory toxicities based on local laboratory assessments), during
first-line treatment
Incidence of ATA response to MPDL3280A and potential correlation with pharmacokinetics,
safety, and efficacy parameters
Pharmacokinetic Outcome Measures
The pharmacokinetic outcome measures for this study are as follows:
Maximum MPDL3280A serum concentration (Cmax) after infusion on Cycle 1, Day 1
Minimum MPDL3280A serum concentration (Cmin) prior to the infusion on Day 1 of Cycles 1,
2, 4, 8 and every eight cycles thereafter; Day 22 of Cycles 1, 2, and 4; and at study
termination
Bevacizumab Cmax after infusion on Day 1 of Cycles 1 and 2
Bevacizumab Cmin prior to the infusion on Day 1 of Cycles 1 and 2 and at study termination
Inclution Criteria
Inclusion Criteria
Patients must meet the following criteria for study entry:
Signed Informed Consent Form
Unresectable advanced or metastatic RCC with clear-cell histology and/or sarcomatoid
carcinoma (defined below)
Sarcomatoid renal cell carcinoma is defined as any histologic type of renal cell
carcinoma containing a foci of high-grade malignant spindle cells encompassing
20% of the area relative to the entire tumor area. (See the protocol for further
guidelines regarding defining sarcomatoid histology.)
Evaluable MSKCC risk score (i.e., “Motzer” score)
All MSKCC risk scores are included
Patients with good risk MSKCC (risk score 0) will comprise no more than 20% of the
study population
Definitive diagnosis of RCC on the basis of a representative, formalin-fixed,
paraffin-embedded tumor specimen accompanied by an associated pathology report
collected within 24 months prior to Cycle 1, Day 1 available at the study site that allows
determination of PD-L1 expression status (IC) (required prior to randomization)
The archival specimen must contain adequate viable tumor tissue to establish PD-L1
expression status by a central laboratory prior to randomization.
The specimen may consist of a tissue block (preferred) or at least 15 unstained,
serial sections.
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 embedded into a single paraffin block should be submitted for evaluation.
Tumor tissue from bone metastases is not evaluable for PD-L1 expression and is
therefore not acceptable.
If the archival tissue was acquired 24 months prior to Cycle 1, Day 1, the patient may
still be eligible provided the patient is willing to consent to and undergo a pre-treatment
core or excisional biopsy of the tumor. If the location of the tumor renders the tumor
biopsy medically unsafe, eligibility may be provided with Medical Monitor approval. A
local analysis to confirm the diagnosis of RCC is required.
Measurable disease, as defined by RECIST v1.1
Age 18 years
Karnofsky performance status 70
Ability and capacity to comply with study and follow-up procedures
Adequate hematologic and end-organ function, defined by the following laboratory results
obtained within 28 calendar days prior to the first study treatment:
ANC 1500 cells/L (without granulocyte colony-stimulating factor support within
2 weeks prior to Cycle 1, Day 1)
WBC counts 2500/L
Lymphocyte count 300/L
Platelet count 100,000/L (without transfusion within 2 weeks prior to Cycle 1, Day 1)
Hemoglobin 9.0 g/dL
AST,ALT, and alkaline phosphatase 2.5theupperlimit ofnormal(ULN), with
the following exceptions:
Patients with documented liver metastases: AST andALT 5ULN
Patients with documented liver or bone metastases: alkaline phosphatase
5ULN
Serumbilirubin1.5ULN
Patients with known Gilbert disease who have serum bilirubin level 3
ULNmaybeenrolled.
INR and aPTT 1.5ULN, unless on a stable dose of
warfarinSerum albumin2.5g/dL
Creatinine clearance 30 mL/min (Cockcroft-Gault formula or based on 24-hour urine
collection)
For women who are not postmenopausal ( 12 months of non-therapy-induced amenorrhea)
or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or
use single or combined 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 MPDL3280A or
bevacizumab, or at least 30 days after the last dose of sunitinib.
Abstinence is only acceptable if it is in line with 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.
Examples of contraceptive methods with a failure rate of 1% per year include tubal
ligation, male sterilization, hormonal implants, established, proper use of combined
oral or injected hormonal contraceptives, and certain intrauterine devices. Alternatively,
two methods (e.g., two barrier methods such as a condom and a cervical cap) may be
combined to achieve a failure rate of 1% per year. Barrier methods must always be
supplemented with the use of a spermicide.
Patients must meet the following criteria for study entry:
Signed Informed Consent Form
Unresectable advanced or metastatic RCC with clear-cell histology and/or sarcomatoid
carcinoma (defined below)
Sarcomatoid renal cell carcinoma is defined as any histologic type of renal cell
carcinoma containing a foci of high-grade malignant spindle cells encompassing
20% of the area relative to the entire tumor area. (See the protocol for further
guidelines regarding defining sarcomatoid histology.)
Evaluable MSKCC risk score (i.e., “Motzer” score)
All MSKCC risk scores are included
Patients with good risk MSKCC (risk score 0) will comprise no more than 20% of the
study population
Definitive diagnosis of RCC on the basis of a representative, formalin-fixed,
paraffin-embedded tumor specimen accompanied by an associated pathology report
collected within 24 months prior to Cycle 1, Day 1 available at the study site that allows
determination of PD-L1 expression status (IC) (required prior to randomization)
The archival specimen must contain adequate viable tumor tissue to establish PD-L1
expression status by a central laboratory prior to randomization.
The specimen may consist of a tissue block (preferred) or at least 15 unstained,
serial sections.
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 embedded into a single paraffin block should be submitted for evaluation.
Tumor tissue from bone metastases is not evaluable for PD-L1 expression and is
therefore not acceptable.
If the archival tissue was acquired 24 months prior to Cycle 1, Day 1, the patient may
still be eligible provided the patient is willing to consent to and undergo a pre-treatment
core or excisional biopsy of the tumor. If the location of the tumor renders the tumor
biopsy medically unsafe, eligibility may be provided with Medical Monitor approval. A
local analysis to confirm the diagnosis of RCC is required.
Measurable disease, as defined by RECIST v1.1
Age 18 years
Karnofsky performance status 70
Ability and capacity to comply with study and follow-up procedures
Adequate hematologic and end-organ function, defined by the following laboratory results
obtained within 28 calendar days prior to the first study treatment:
ANC 1500 cells/L (without granulocyte colony-stimulating factor support within
2 weeks prior to Cycle 1, Day 1)
WBC counts 2500/L
Lymphocyte count 300/L
Platelet count 100,000/L (without transfusion within 2 weeks prior to Cycle 1, Day 1)
Hemoglobin 9.0 g/dL
AST,ALT, and alkaline phosphatase 2.5theupperlimit ofnormal(ULN), with
the following exceptions:
Patients with documented liver metastases: AST andALT 5ULN
Patients with documented liver or bone metastases: alkaline phosphatase
5ULN
Serumbilirubin1.5ULN
Patients with known Gilbert disease who have serum bilirubin level 3
ULNmaybeenrolled.
INR and aPTT 1.5ULN, unless on a stable dose of
warfarinSerum albumin2.5g/dL
Creatinine clearance 30 mL/min (Cockcroft-Gault formula or based on 24-hour urine
collection)
For women who are not postmenopausal ( 12 months of non-therapy-induced amenorrhea)
or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or
use single or combined 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 MPDL3280A or
bevacizumab, or at least 30 days after the last dose of sunitinib.
Abstinence is only acceptable if it is in line with 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.
Examples of contraceptive methods with a failure rate of 1% per year include tubal
ligation, male sterilization, hormonal implants, established, proper use of combined
oral or injected hormonal contraceptives, and certain intrauterine devices. Alternatively,
two methods (e.g., two barrier methods such as a condom and a cervical cap) may be
combined to achieve a failure rate of 1% per year. Barrier methods must always be
supplemented with the use of a spermicide.
Exclusion Criteria
Exclusion Criteria
Disease-SpecificExclusions
No prior treatment with active or experimental systemic agents, including treatment in the
neoadjuvant or adjuvant setting. Prior treatment with placebo in adjuvant setting is allowed.
Radiotherapy for RCC within 14 calendar days prior to Cycle 1, Day 1
Active or untreated CNS metastases as determined by computed tomography (CT) 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, cerebellum, or within 10 mm of the
optic apparatus (optic nerves and chiasm)
No history of intracranial or spinal cord hemorrhage
No ongoing requirement for dexamethasone as therapy for CNS disease; anticonvulsants at a stable dose are allowed
No evidence of significant vasogenic edema
No stereotactic radiation, whole-brain radiation or neurosurgical resection with
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
Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or
metastases causing nerve impingement) should be treated at least 14 days prior to Cycle 1,
Day 1.
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage
procedures (once monthly or more frequently)
Uncontrolled hypercalcemia ( 1.5 mmol/L ionized calcium or Ca 12 mg/dL or corrected
serum calcium greater than the upper limit of normal]) or symptomatic hypercalcemia
refractory to bisphosphonate therapy or denosumab
Patients who are currently receiving bisphosphonate therapy without current
hypercalcemia (corrected serum calcium greater than the upper limit of normal) are
eligible. Patients currently receiving denosumab must substitute a bisphosphonate (if
eligible)
Malignancies other than RCC within 5 years prior to Cycle 1, Day 1, with the exception of
those with a negligible risk of metastasis or death, treated with expected curative outcome
(such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin
cancer, localized prostate cancer treated with curative intent, ductal carcinoma in situ of the
breast treated surgically with curative intent). Contact the Medical Monitor if there are
concerns or if clarification is needed.
General Medical Exclusions
Life expectancy of 12 weeks
Current, recent (within 4 weeks of Cycle 1, Day 1), or planned participation in another
experimental drug study
Pregnant and lactating , or intending to become pregnant during the study
Women who are not postmenopausal (12 months of non-therapy-induced amenorrhea) or
surgically sterile must have a negative serum pregnancy test result within 7 days prior to
initiation of study drug.
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 MPDL3280A 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 (see the protocol for a more comprehensive list of autoimmune
diseases)
Patients with a history of autoimmune-related hypothyroidism on a stable dose of
thyroid replacement hormone are eligible for this study.
Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen
may be eligible for this study.
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans),
drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on
screening chest CT scan
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
Positive test for HIV
Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface
antigen [HBsAg] test at screening)
Patients with past/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.
HBV DNA must be obtained in patients with positive hepatitis B core antibody prior to
Cycle 1, Day 1.
Patients with controlled Type I diabetes mellitus on a stable insulin regimen may be
eligible for this study
Patients with active hepatitis C
Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR)
analysis is negative for HCV RNA.
Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to
hospitalization for complications of infection, bacteremia, or severe pneumonia
Signs or symptoms of infection (including active tuberculosis) within 2 weeks prior to
Cycle 1, Day 1
Received therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1
Patients receiving routine antibiotic prophylaxis (e.g., to prevent chronic obstructive
pulmonary disease exacerbation or for dental extraction) are eligible.
Significant cardiovascular or cerebrovascular disease, such as New York Heart Association
cardiac disease (Class II or greater), unstable angina, myocardial infarction or
cerebrovascular events within the previous 6 months or unstable arrhythmias within the
previous 3 months.
Patients with known coronary artery disease, arrhythmias, congestive heart failure not
meeting the above criteria must be on a stable medical regimen that is optimized in the
opinion of the treating physician, in consultation with a cardiologist if appropriate.
Baseline evaluation of left ventricular ejection fraction should be considered for all
patients, especially in those with cardiac risk factors and/or history of coronary artery
disease.
Patients with known left ventricular ejection fraction 50%
Major surgical procedure other than for diagnosis within 21 days prior to Cycle 1, Day 1, or
planned procedure or surgery during the study
Prior allogeneic stem cell or solid organ transplant
Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
Influenza vaccination should be given during influenza season only. Patients must not
receive live, attenuated influenza vaccine within 4 weeks prior to Cycle 1, Day 1 or at
any time during the study.
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
Disease-SpecificExclusions
No prior treatment with active or experimental systemic agents, including treatment in the
neoadjuvant or adjuvant setting. Prior treatment with placebo in adjuvant setting is allowed.
Radiotherapy for RCC within 14 calendar days prior to Cycle 1, Day 1
Active or untreated CNS metastases as determined by computed tomography (CT) 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, cerebellum, or within 10 mm of the
optic apparatus (optic nerves and chiasm)
No history of intracranial or spinal cord hemorrhage
No ongoing requirement for dexamethasone as therapy for CNS disease; anticonvulsants at a stable dose are allowed
No evidence of significant vasogenic edema
No stereotactic radiation, whole-brain radiation or neurosurgical resection with
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
Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or
metastases causing nerve impingement) should be treated at least 14 days prior to Cycle 1,
Day 1.
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage
procedures (once monthly or more frequently)
Uncontrolled hypercalcemia ( 1.5 mmol/L ionized calcium or Ca 12 mg/dL or corrected
serum calcium greater than the upper limit of normal]) or symptomatic hypercalcemia
refractory to bisphosphonate therapy or denosumab
Patients who are currently receiving bisphosphonate therapy without current
hypercalcemia (corrected serum calcium greater than the upper limit of normal) are
eligible. Patients currently receiving denosumab must substitute a bisphosphonate (if
eligible)
Malignancies other than RCC within 5 years prior to Cycle 1, Day 1, with the exception of
those with a negligible risk of metastasis or death, treated with expected curative outcome
(such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin
cancer, localized prostate cancer treated with curative intent, ductal carcinoma in situ of the
breast treated surgically with curative intent). Contact the Medical Monitor if there are
concerns or if clarification is needed.
General Medical Exclusions
Life expectancy of 12 weeks
Current, recent (within 4 weeks of Cycle 1, Day 1), or planned participation in another
experimental drug study
Pregnant and lactating , or intending to become pregnant during the study
Women who are not postmenopausal (12 months of non-therapy-induced amenorrhea) or
surgically sterile must have a negative serum pregnancy test result within 7 days prior to
initiation of study drug.
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 MPDL3280A 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 (see the protocol for a more comprehensive list of autoimmune
diseases)
Patients with a history of autoimmune-related hypothyroidism on a stable dose of
thyroid replacement hormone are eligible for this study.
Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen
may be eligible for this study.
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans),
drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on
screening chest CT scan
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
Positive test for HIV
Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface
antigen [HBsAg] test at screening)
Patients with past/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.
HBV DNA must be obtained in patients with positive hepatitis B core antibody prior to
Cycle 1, Day 1.
Patients with controlled Type I diabetes mellitus on a stable insulin regimen may be
eligible for this study
Patients with active hepatitis C
Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR)
analysis is negative for HCV RNA.
Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to
hospitalization for complications of infection, bacteremia, or severe pneumonia
Signs or symptoms of infection (including active tuberculosis) within 2 weeks prior to
Cycle 1, Day 1
Received therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1
Patients receiving routine antibiotic prophylaxis (e.g., to prevent chronic obstructive
pulmonary disease exacerbation or for dental extraction) are eligible.
Significant cardiovascular or cerebrovascular disease, such as New York Heart Association
cardiac disease (Class II or greater), unstable angina, myocardial infarction or
cerebrovascular events within the previous 6 months or unstable arrhythmias within the
previous 3 months.
Patients with known coronary artery disease, arrhythmias, congestive heart failure not
meeting the above criteria must be on a stable medical regimen that is optimized in the
opinion of the treating physician, in consultation with a cardiologist if appropriate.
Baseline evaluation of left ventricular ejection fraction should be considered for all
patients, especially in those with cardiac risk factors and/or history of coronary artery
disease.
Patients with known left ventricular ejection fraction 50%
Major surgical procedure other than for diagnosis within 21 days prior to Cycle 1, Day 1, or
planned procedure or surgery during the study
Prior allogeneic stem cell or solid organ transplant
Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
Influenza vaccination should be given during influenza season only. Patients must not
receive live, attenuated influenza vaccine within 4 weeks prior to Cycle 1, Day 1 or at
any time during the study.
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
The Estimated Number of Participants
-
Taiwan
12 participants
-
Global
900 participants
