Clinical Trials List
Protocol NumberXL184–312
NCT Number(ClinicalTrials.gov Identfier)NCT03755791
2019-03-01 - 2023-12-31
Phase III
Recruiting7
Terminated2
ICD-10C22.0
Liver cell carcinoma
A Randomized, Controlled Phase 3 Study of Cabozantinib (XL184) in Combination with Atezolizumab versus Sorafenib in Subjects with Advanced Hepatocellular Carcinoma Who Have Not Received Previous Systemic Anticancer Therapy
-
Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
-
Sponsor
Exelixis, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chiu Hung Chiu 無
- Yih-Jyh Lin 無
- 簡世杰 無
- 劉奕廷 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Jen-Shi Chen 無
- 彭夣婷 無
- Cheng-Lung Hsu 無
- Wen-Chi Chou 無
- Chia-Hsun Hsieh 無
- Ming-Mo Hou 無
- 呂嘉偉 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Co-Principal Investigator
- San-Chi Chen 無
- Ming-Huang Chen 無
- Yee Chao Division of Hematology & Oncology
- Rheun-Chuan Lee 無
- Pei-Chang Lee 無
- Yi-Hsiang Huang 無
- Chung-Pin Li 無
- Yun-Cheng Hsieh 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 吳佳哲 無
- 陳彥豪 無
- 劉建廷 無
- Tai-Jan Chiu 無
- Yu-Li Su 無
- Shau-Hsuan Li 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- TENG-YU LEE 無
- 蘇德晟 無
- 黃儀倢 無
- 呂宜達 無
- CHUNG-HSIN CHANG 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Ying-Chun Shen 無
- TSUNG-HAO LIU 無
- 林宗哲 無
- Chien-Hung Chen 無
- Chiun Hsu 無
- YU-YUN SHAO 無
- Chih-Hung Hsu 無
- 呂理駿 無
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Advanced Hepatocellular Carcinoma
Objectives
This is a multicenter, randomized, open-label, controlled Phase 3 trial of cabozantinib in combination with atezolizumab versus sorafenib in adults with advanced HCC who have not received previous systemic anticancer therapy in the advanced HCC setting. The primary objective of this study is to evaluate the effect of cabozantinib in combination with atezolizumab on the duration of progression-free survival (PFS) and duration of overall survival (OS) versus sorafenib. The secondary objective is to evaluate the activity of single-agent cabozantinib compared with sorafenib in this patient population.
Test Drug
Cabozantinib (XL184) 20mg and 60mg tablet; Atezolizumab 1200mg/ 20ml solution for IV infusion
Active Ingredient
Atezolizumab
Cabozantinib
Cabozantinib
Dosage Form
tablet
solution for IV infusion
solution for IV infusion
Dosage
20
1200
1200
Endpoints
Primary Efficacy Endpoints:
• Duration of PFS per Response Evaluable Criteria in Solid Tumors version 1.1 (RECIST
1.1), by BIRC
• Duration of OS
Secondary Efficacy Endpoints:
• Objective response rate (ORR) per RECIST 1.1 by BIRC
• Duration of PFS per Response Evaluable Criteria in Solid Tumors version 1.1 (RECIST
1.1), by BIRC
• Duration of OS
Secondary Efficacy Endpoints:
• Objective response rate (ORR) per RECIST 1.1 by BIRC
Inclution Criteria
Inclusion Criteria
1. Histological or cytological diagnosis of HCC.
2. The subject has disease that is not amenable to a curative treatment approach (eg, transplant,
surgery, ablation therapy) or locoregional therapy (eg, TACE).
3. The subject is receiving antiviral therapy per local standard of care if the subject has active
HBV infection (defined by HBsAg positive); the subject must have HBV DNA < 500 IU/mL.
4. Measurable disease per RECIST 1.1 as determined by the Investigator.
5. Barcelona Clinic Liver Cancer (BCLC) stage Category B or C (Appendix J).
6. Child-Pugh Score of A (Appendix K).
7. Recovery to baseline or ≤ Grade 1 per Common Terminology Criteria for Adverse Events
(CTCAE) v5 from toxicities related to any prior treatments, unless AE(s) are clinically
nonsignificant and/or stable on supportive therapy as determined by the Investigator.
8. Age eighteen years or older on the day of consent.
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
10. Adequate organ and marrow function, based upon meeting all of the following laboratory
criteria within 14 days prior to randomization:
a. Absolute neutrophil count (ANC) ≥ 1500/µL (≥ 1.5 GI/L) without granulocyte
colony-stimulating factor support within 2 weeks before screening laboratory sample
collection.
b. White blood cell (WBC) count ≥ 2000/µL (≥ 2.0 GI/L).
c. Platelets ≥ 60,000/µL (≥ 60 GI/L) without transfusion within 2 weeks before screening
laboratory sample collection.
d. Hemoglobin ≥ 9 g/dL (≥ 90 g/L) without transfusion within 2 weeks before screening
laboratory sample collection.
e. Hemoglobin A1c (HbA1c) ≤ 8% within 28 days before randomization (if HbA1c results
are unavailable [eg, hemoglobin variant], a fasting serum glucose ≤ 160 mg/dL)
f. Alanine aminotransferase (ALT), AST, and alkaline phosphatase (ALP) ≤ 5 × upper limit
of normal (ULN).
g. Total bilirubin ≤ 2 mg/dL (≤ 34.2 µmol/L).
h. Serum albumin ≥ 2.8 g/dL (≥ 28 g/L).
i. Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 40 mL/min (≥ 0.67
mL/sec) using the Cockcroft-Gault equation (see Table 5-2).
j. Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h protein
≤ 1 g.
11. Capable of understanding and complying with the protocol requirements and must have
signed the informed consent document prior to any screening assessment except those
procedures performed as standard of care within the screening window.
12. Sexually active fertile subjects and their partners must agree to use highly effective methods
of contraception that alone or in combination result in a failure rate of less than 1% per year
when used consistently and correctly (see Appendix I) during the course of the study and for
5 months after the last dose of study treatment. An additional contraceptive method, such as a
barrier method (eg, condom), is recommended.
13. Female subjects of childbearing potential must not be pregnant at screening. Females of
childbearing potential are defined as premenopausal females capable of becoming pregnant
(ie, females who have had any evidence of menses in the past 12 months, with the exception
of those who had prior hysterectomy). However, women who have been amenorrheic for
12 or more months are still considered to be of childbearing potential if the amenorrhea is
possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or
other reasons.
1. Histological or cytological diagnosis of HCC.
2. The subject has disease that is not amenable to a curative treatment approach (eg, transplant,
surgery, ablation therapy) or locoregional therapy (eg, TACE).
3. The subject is receiving antiviral therapy per local standard of care if the subject has active
HBV infection (defined by HBsAg positive); the subject must have HBV DNA < 500 IU/mL.
4. Measurable disease per RECIST 1.1 as determined by the Investigator.
5. Barcelona Clinic Liver Cancer (BCLC) stage Category B or C (Appendix J).
6. Child-Pugh Score of A (Appendix K).
7. Recovery to baseline or ≤ Grade 1 per Common Terminology Criteria for Adverse Events
(CTCAE) v5 from toxicities related to any prior treatments, unless AE(s) are clinically
nonsignificant and/or stable on supportive therapy as determined by the Investigator.
8. Age eighteen years or older on the day of consent.
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
10. Adequate organ and marrow function, based upon meeting all of the following laboratory
criteria within 14 days prior to randomization:
a. Absolute neutrophil count (ANC) ≥ 1500/µL (≥ 1.5 GI/L) without granulocyte
colony-stimulating factor support within 2 weeks before screening laboratory sample
collection.
b. White blood cell (WBC) count ≥ 2000/µL (≥ 2.0 GI/L).
c. Platelets ≥ 60,000/µL (≥ 60 GI/L) without transfusion within 2 weeks before screening
laboratory sample collection.
d. Hemoglobin ≥ 9 g/dL (≥ 90 g/L) without transfusion within 2 weeks before screening
laboratory sample collection.
e. Hemoglobin A1c (HbA1c) ≤ 8% within 28 days before randomization (if HbA1c results
are unavailable [eg, hemoglobin variant], a fasting serum glucose ≤ 160 mg/dL)
f. Alanine aminotransferase (ALT), AST, and alkaline phosphatase (ALP) ≤ 5 × upper limit
of normal (ULN).
g. Total bilirubin ≤ 2 mg/dL (≤ 34.2 µmol/L).
h. Serum albumin ≥ 2.8 g/dL (≥ 28 g/L).
i. Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 40 mL/min (≥ 0.67
mL/sec) using the Cockcroft-Gault equation (see Table 5-2).
j. Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h protein
≤ 1 g.
11. Capable of understanding and complying with the protocol requirements and must have
signed the informed consent document prior to any screening assessment except those
procedures performed as standard of care within the screening window.
12. Sexually active fertile subjects and their partners must agree to use highly effective methods
of contraception that alone or in combination result in a failure rate of less than 1% per year
when used consistently and correctly (see Appendix I) during the course of the study and for
5 months after the last dose of study treatment. An additional contraceptive method, such as a
barrier method (eg, condom), is recommended.
13. Female subjects of childbearing potential must not be pregnant at screening. Females of
childbearing potential are defined as premenopausal females capable of becoming pregnant
(ie, females who have had any evidence of menses in the past 12 months, with the exception
of those who had prior hysterectomy). However, women who have been amenorrheic for
12 or more months are still considered to be of childbearing potential if the amenorrhea is
possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or
other reasons.
Exclusion Criteria
Exclusion Criteria
1. Fibrolamellar carcinoma, sarcomatoid HCC or mixed hepatocellular cholangiocarcinoma.
2. Prior systemic anticancer therapy for advanced HCC including but not limited to
chemotherapy, small molecule kinase inhibitors, and ICIs. Subjects who have received local
intratumoral or arterial chemotherapy are eligible.
3. Hepatic encephalopathy or requirement for medication for prevention or control of
encephalopathy within 6 months before randomization.
4. Clinically meaningful ascites (ie, ascites requiring paracentesis or escalation in diuretics)
within 6 months before randomization.
5. Subjects who have received any local anticancer therapy including surgery, PEI, RFA,
MWA, transarterial [chemo] embolization, or radiotherapy within 28 days prior to
randomization
6. Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within
8 weeks prior to randomization. Subjects with clinically relevant ongoing complications from
prior radiation therapy are not eligible.
7. Known brain metastases or cranial epidural disease unless adequately treated with
radiotherapy and/or surgery (including radiosurgery) and stable for at least 8 weeks prior to
randomization. Subjects who are neurologically symptomatic or are receiving systemic
corticosteroid treatment at the planned time of randomization are not eligible.
8. Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and
Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel), except for the following allowed
anticoagulants:
• Low-dose aspirin for cardioprotection (per local applicable guidelines) and low-dose low
molecular weight heparins (LMWH)
9. Administration of a live, attenuated vaccine within 30 days prior to randomization.
10. Any subject who cannot be evaluated by either triphasic liver computed tomography (CT) or
triphasic liver magnetic resonance imaging (MRI) because of allergy or other
contraindication to both CT and MRI contrast agents.
11. The subject has uncontrolled, significant intercurrent or recent (within the last 3 months
before randomization [unless otherwise specified below]) illness including, but not limited to,
the following conditions:
a. Cardiovascular disorders:
i. Congestive heart failure (CHF) class III or IV as defined by the New York Heart
Association, unstable angina pectoris, serious cardiac arrhythmias.
ii. Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg
systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
iii. Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or
other ischemic event or thromboembolic event (eg, deep vein thrombosis [DVT],
pulmonary embolism) within 6 months before randomization.
b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation
or fistula formation:
i. Tumors invading the GI-tract, active peptic ulcer disease, inflammatory bowel
disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute
pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet
obstruction.
ii. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess
within 6 months prior to randomization. Complete healing of an intra-abdominal
abscess must be confirmed prior to randomization.
iii. Gastric or esophageal varices that are untreated or incompletely treated with bleeding
or high risk for bleeding. Subjects treated with adequate endoscopic therapy
(according to institutional standards) without any episodes of recurrent GI bleeding
requiring transfusion or hospitalization for at least 6 months before randomization are
eligible.
c. Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml)
of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within
3 months before randomization.
d. Cavitating pulmonary lesion(s) or known endobronchial disease manifestation.
e. Lesions invading major blood vessel, including, but not limited to: inferior vena cava,
pulmonary artery, or aorta. Subjects with lesions invading the intrahepatic vasculature,
including portal vein, hepatic vein, and hepatic artery, are eligible.
f. Other clinically significant disorders such as:
i. Active or history of autoimmune disease or immune deficiency, including, but not
limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease,
antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren’s syndrome,
Guillain-Barré syndrome, or multiple sclerosis (see Appendix E for a more
comprehensive list of autoimmune diseases and immune deficiencies). Subjects with
the following conditions are eligible for the study:
• A history of autoimmune-related hypothyroidism and on thyroid replacement
hormone
• Controlled Type 1 diabetes mellitus and on an insulin regimen
• Asthma that requires intermittent use of bronchodilators
• Eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic
manifestations only provided all of following are true:
o Rash covers < 10% of body surface area
o Disease is well controlled at baseline and requires only low-potency topical
corticosteroids
o No occurrence of acute exacerbations of the underlying condition requiring
psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents,
oral calcineurin inhibitors, or high potency or oral corticosteroids within the
previous 12 months
ii. Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily
prednisone equivalent) or other immunosuppressive medications within 14 days
before randomization.
Note: Inhaled, intranasal, intra-articular, and topical corticosteroids and
mineralocorticoids are permitted.
Transient use of systemic corticosteroids for allergic conditions such as contrast
allergy is allowed.
iii. Active infection requiring systemic treatment, known history of infection with human
immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness, or a known positive test for tuberculosis due to tuberculosis
infection. Subjects with active hepatitis B virus infection controlled with antiviral
therapy are eligible (see Inclusion Criterion 3). Subjects with active, uncontrolled
hepatitis C virus infection are eligible provided liver function meets eligibility criteria
and are receiving management of the disease per local institutional practice (note:
antiviral treatment for HCV is allowed with Sponsor approval).
iv. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest CT scan
v. Serious non-healing wound/ulcer/bone fracture.
vi. Malabsorption syndrome.
vii. Free thyroxine (FT4) outside the laboratory normal reference range. Asymptomatic
subjects with FT4 abnormalities can be eligible after sponsor approval.
viii. Moderate to severe hepatic impairment (Child-Pugh B or C).
ix. Requirement for hemodialysis or peritoneal dialysis.
x. History of solid organ transplant including liver transplant, or allogeneic stem cell
transplant.
12. Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks before
randomization. Minor surgeries within 10 days before randomization. Subjects must have
complete wound healing from major surgery or minor surgery before randomization. Subjects
with clinically relevant ongoing complications from prior surgery are not eligible.
13. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per
electrocardiogram (ECG) within 14 days before randomization.
Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs
at intervals of approximately 3 min must be performed within 30 min after the initial ECG,
and the average of these three consecutive results for QTcF will be used to determine
eligibility
14. History of psychiatric illness likely to interfere with ability to comply with protocol
requirements or give informed consent
15. Pregnant or breastfeeding females.
16. Inability to swallow tablets.
17. Previously identified allergy or hypersensitivity to components of the study treatment
formulations or history of severe hypersensitivity to monoclonal antibodies.
18. Any other active malignancy at time of randomization or diagnosis of another malignancy
within 2 years before randomization that requires active treatment, except for superficial skin
cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
1. Fibrolamellar carcinoma, sarcomatoid HCC or mixed hepatocellular cholangiocarcinoma.
2. Prior systemic anticancer therapy for advanced HCC including but not limited to
chemotherapy, small molecule kinase inhibitors, and ICIs. Subjects who have received local
intratumoral or arterial chemotherapy are eligible.
3. Hepatic encephalopathy or requirement for medication for prevention or control of
encephalopathy within 6 months before randomization.
4. Clinically meaningful ascites (ie, ascites requiring paracentesis or escalation in diuretics)
within 6 months before randomization.
5. Subjects who have received any local anticancer therapy including surgery, PEI, RFA,
MWA, transarterial [chemo] embolization, or radiotherapy within 28 days prior to
randomization
6. Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within
8 weeks prior to randomization. Subjects with clinically relevant ongoing complications from
prior radiation therapy are not eligible.
7. Known brain metastases or cranial epidural disease unless adequately treated with
radiotherapy and/or surgery (including radiosurgery) and stable for at least 8 weeks prior to
randomization. Subjects who are neurologically symptomatic or are receiving systemic
corticosteroid treatment at the planned time of randomization are not eligible.
8. Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and
Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel), except for the following allowed
anticoagulants:
• Low-dose aspirin for cardioprotection (per local applicable guidelines) and low-dose low
molecular weight heparins (LMWH)
9. Administration of a live, attenuated vaccine within 30 days prior to randomization.
10. Any subject who cannot be evaluated by either triphasic liver computed tomography (CT) or
triphasic liver magnetic resonance imaging (MRI) because of allergy or other
contraindication to both CT and MRI contrast agents.
11. The subject has uncontrolled, significant intercurrent or recent (within the last 3 months
before randomization [unless otherwise specified below]) illness including, but not limited to,
the following conditions:
a. Cardiovascular disorders:
i. Congestive heart failure (CHF) class III or IV as defined by the New York Heart
Association, unstable angina pectoris, serious cardiac arrhythmias.
ii. Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg
systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
iii. Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or
other ischemic event or thromboembolic event (eg, deep vein thrombosis [DVT],
pulmonary embolism) within 6 months before randomization.
b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation
or fistula formation:
i. Tumors invading the GI-tract, active peptic ulcer disease, inflammatory bowel
disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute
pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet
obstruction.
ii. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess
within 6 months prior to randomization. Complete healing of an intra-abdominal
abscess must be confirmed prior to randomization.
iii. Gastric or esophageal varices that are untreated or incompletely treated with bleeding
or high risk for bleeding. Subjects treated with adequate endoscopic therapy
(according to institutional standards) without any episodes of recurrent GI bleeding
requiring transfusion or hospitalization for at least 6 months before randomization are
eligible.
c. Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml)
of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within
3 months before randomization.
d. Cavitating pulmonary lesion(s) or known endobronchial disease manifestation.
e. Lesions invading major blood vessel, including, but not limited to: inferior vena cava,
pulmonary artery, or aorta. Subjects with lesions invading the intrahepatic vasculature,
including portal vein, hepatic vein, and hepatic artery, are eligible.
f. Other clinically significant disorders such as:
i. Active or history of autoimmune disease or immune deficiency, including, but not
limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease,
antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren’s syndrome,
Guillain-Barré syndrome, or multiple sclerosis (see Appendix E for a more
comprehensive list of autoimmune diseases and immune deficiencies). Subjects with
the following conditions are eligible for the study:
• A history of autoimmune-related hypothyroidism and on thyroid replacement
hormone
• Controlled Type 1 diabetes mellitus and on an insulin regimen
• Asthma that requires intermittent use of bronchodilators
• Eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic
manifestations only provided all of following are true:
o Rash covers < 10% of body surface area
o Disease is well controlled at baseline and requires only low-potency topical
corticosteroids
o No occurrence of acute exacerbations of the underlying condition requiring
psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents,
oral calcineurin inhibitors, or high potency or oral corticosteroids within the
previous 12 months
ii. Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily
prednisone equivalent) or other immunosuppressive medications within 14 days
before randomization.
Note: Inhaled, intranasal, intra-articular, and topical corticosteroids and
mineralocorticoids are permitted.
Transient use of systemic corticosteroids for allergic conditions such as contrast
allergy is allowed.
iii. Active infection requiring systemic treatment, known history of infection with human
immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness, or a known positive test for tuberculosis due to tuberculosis
infection. Subjects with active hepatitis B virus infection controlled with antiviral
therapy are eligible (see Inclusion Criterion 3). Subjects with active, uncontrolled
hepatitis C virus infection are eligible provided liver function meets eligibility criteria
and are receiving management of the disease per local institutional practice (note:
antiviral treatment for HCV is allowed with Sponsor approval).
iv. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest CT scan
v. Serious non-healing wound/ulcer/bone fracture.
vi. Malabsorption syndrome.
vii. Free thyroxine (FT4) outside the laboratory normal reference range. Asymptomatic
subjects with FT4 abnormalities can be eligible after sponsor approval.
viii. Moderate to severe hepatic impairment (Child-Pugh B or C).
ix. Requirement for hemodialysis or peritoneal dialysis.
x. History of solid organ transplant including liver transplant, or allogeneic stem cell
transplant.
12. Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks before
randomization. Minor surgeries within 10 days before randomization. Subjects must have
complete wound healing from major surgery or minor surgery before randomization. Subjects
with clinically relevant ongoing complications from prior surgery are not eligible.
13. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per
electrocardiogram (ECG) within 14 days before randomization.
Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs
at intervals of approximately 3 min must be performed within 30 min after the initial ECG,
and the average of these three consecutive results for QTcF will be used to determine
eligibility
14. History of psychiatric illness likely to interfere with ability to comply with protocol
requirements or give informed consent
15. Pregnant or breastfeeding females.
16. Inability to swallow tablets.
17. Previously identified allergy or hypersensitivity to components of the study treatment
formulations or history of severe hypersensitivity to monoclonal antibodies.
18. Any other active malignancy at time of randomization or diagnosis of another malignancy
within 2 years before randomization that requires active treatment, except for superficial skin
cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
The Estimated Number of Participants
-
Taiwan
62 participants
-
Global
840 participants
