Clinical Trials List
Protocol NumberD4190C00002
NCT Number(ClinicalTrials.gov Identfier)NCT01938612
2015-07-01 - 2019-03-31
Phase I
Not yet recruiting3
ICD-10C80.1
Malignant (primary) neoplasm, unspecified
A Phase I, Open-Label, Multicentre Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MEDI4736 in Patients with Advanced Solid Tumours
-
Trial Applicant
-
Sponsor
AstraZeneca
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Shang-Yin Wu Division of Hematology & Oncology
- Nai-Jung Chiang Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- Wu-Chou Su Division of Hematology & Oncology
- Yau-Lin Tseng Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
- 姜乃榕 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Audit
None
Co-Principal Investigator
- Tsai-Sheng Yang Division of Hematology & Oncology
- Chia-Hsun Hsieh Division of Hematology & Oncology
- Wen-Cheng Chang Division of Hematology & Oncology
- Wen-Chi Shen Division of Hematology & Oncology
- Ming-Mo Hou Division of Hematology & Oncology
- Hung-Chih Hsu Division of Hematology & Oncology
- Hsien-Kun Chang Division of Hematology & Oncology
- Wen-Chi Chou Division of Hematology & Oncology
- Yung-Chia Kao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
7 Not yet recruiting
Audit
None
Co-Principal Investigator
- Chia-Chi Lin Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
- Kun-Huei Yeh Division of Hematology & Oncology
- TA-CHEN HUANG Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Audit
None
Condition/Disease
Advanced Solid Tumours
Objectives
Primary objective
To evaluate the safety and tolerability of MEDI4736 when given to patients with
advanced solid tumours.
Secondary objective(s)
1. To identify the maximum tolerated dose (MTD) or optimal biological dose (OBD) of
MEDI4736 in patients with advanced solid tumours, if possible.
2. To describe the pharmacokinetics (PK) of MEDI4736 in patients with advanced solid
tumours.
3. To determine the immunogenicity (IM) of MEDI4736 in patients with advanced
solid tumours.
4. To evaluate the antitumour activity of MEDI4736 in patients with advanced solid
tumours.
Exploratory objective(s)
1. To evaluate biomarkers that may correlate with activity or prospectively identify
patients likely to respond to MEDI4736 treatment.
2. To explore immune-related Response Evaluation Criteria in Solid Tumours
(irRECIST) as an assessment methodology for antitumour activity of MEDI4736 by
Independent Central Review (ICR)
Test Drug
MEDI4736
Active Ingredient
MEDI4736
Dosage Form
Injection
Dosage
200mg/bottle
Endpoints
1. Primary endpoint(s):
The primary efficacy endpoint in the dose expansion is ORR based on the RECIST 1.1
by the investigators’ assessment. ORR is defined as the number (%) of patients with a
confirmed overall response of CR or PR and will be based on a subset of all treated
patients.
2. Other efficacy variables:
Progression free survival(PFS)
Duration of response (DoR)
Overall survival (OS)
Proportion of patients alive at 12 months
Deep sustained response (DSR)
Proportion of patients alive and progression free at 6 months and 12 months
Best objective response (BoR)
Disease control rate (DCR)
The primary efficacy endpoint in the dose expansion is ORR based on the RECIST 1.1
by the investigators’ assessment. ORR is defined as the number (%) of patients with a
confirmed overall response of CR or PR and will be based on a subset of all treated
patients.
2. Other efficacy variables:
Progression free survival(PFS)
Duration of response (DoR)
Overall survival (OS)
Proportion of patients alive at 12 months
Deep sustained response (DSR)
Proportion of patients alive and progression free at 6 months and 12 months
Best objective response (BoR)
Disease control rate (DCR)
Inclution Criteria
Inclusion Criteria:
For inclusion in the study, patients must fulfil all of the following criteria.
1. Provision of signed and dated, written informed consent prior to any study specific
procedures, including screening evaluations.
2. Men or women at least 20 years of age or older at time of study enrollment.
3. In the dose-escalation phase: patients with advanced solid tumours refractory to
standard treatment, intolerant of standard treatment, or for which no standard therapy
exists.
In the dose-expansion phase: histologically- or cytologically-confirmed advanced or
metastatic biliary tract cancer (BTC), esophagus cancer (EC) (squamous cell
carcinoma) or squamous cell carcinoma of the head and neck (SCCHN).
Patients with BTC must have experienced disease progression during or after
receiving at least 1 platinum based palliative therapy for unresectable disease due
to locally advanced, recurrent or metastatic condition.
Patients with EC (squamous cell carcinoma) must have experienced disease
progression during or after receiving at least 1 platinum based palliative therapy
for unresectable disease due to locally advanced, recurrent or metastatic
condition.
Patients with EC who have disease progression within 24 weeks after completion
of multimodality therapy containing platinum, could be enrolled.
Patients with SCCHN must have experienced disease progression during or after
receiving at least 1 platinum based palliative therapy for recurrent or metastatic
disease.
(For Taiwan, We only enroll EC and BTC patients)
4. BTC, EC and SCCHN dose-expansion cohorts: A minimum of 5-10 subjects with
tumoural PD-L1 expression should be enrolled in each cohort.
5. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 and minimum life
expectancy of 16 weeks.
6. Adequate organ and marrow function as defined below:
- Hemoglobin ≥ 9 g/dL
- Absolute neutrophil count ≥ 1,500/mm3
- Platelet count ≥ 100,000/mm3
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ×
institutional upper limit of normal (ULN) or ≤ 5 × ULN for subjects with liver
metastases
- Total bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN for subjects with pancreatic
adenocarcinoma or ≤ 3 × ULN for subjects with documented/suspected Gilbert’s
disease
- Creatinine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation
or by 24-hour urine collection for determination of creatinine clearance (creatinine
clearance by 24-hour urine collection is prioritized if both data is available)
7. Patients must have at least 1 measurable lesion by RECIST v1.1 criteria. Lesion in a
previously irradiated field can be used as measurable disease provided that there has
been clearly demonstrated progression in the lesion.
8. Females of childbearing potential must use 2 methods of effective contraception as
barrier, intrauterine device or hormonal methods (see Table 1) from screening, and
must agree to continue using such precautions for 90 days after the final dose of
investigational product; cessation of birth control after this point should be discussed
with a responsible physician. Periodic abstinence, the rhythm method, and the
withdrawal method are not acceptable methods of birth control.
- Females of childbearing potential are defined as those who are not surgically sterile
(ie, bilateral oophorectomy, bilateral salpingectomy or complete hysterectomy) or
postmenopausal (defined as 12 months with no menses without an alternative
medical cause).
9. Nonsterilized males must use 2 acceptable methods of effective contraception as
barrier, intrauterine device or hormonal methods (see Table 1) from first dose and for
90 days after receipt of the final dose of investigational product.
10. Tumour sample requirements in the dose-escalation phase:
- Available archived tumour tissue sample or fresh biopsy of a lesion that may not be
used for the purpose of tumour assessment (target lesion).
- Tumour sample requirements in the dose-expansion phase:
- Available unstained archived tumour tissue sample in a quantity sufficient to allow
for analysis. Please refer to the Laboratory Manual for details AND
- A recent tumour biopsy (taken following completion of the most recent therapy)
must also be provided. Tumour lesions used for biopsy should not be lesions used
as RECIST target lesions, unless there are no other lesions suitable for biopsy. If a
RECIST target lesion is used for biopsy the lesion must be ≥ 2 cm in longest
diameter. Please refer to the Laboratory Manual for details.
For inclusion in the study, patients must fulfil all of the following criteria.
1. Provision of signed and dated, written informed consent prior to any study specific
procedures, including screening evaluations.
2. Men or women at least 20 years of age or older at time of study enrollment.
3. In the dose-escalation phase: patients with advanced solid tumours refractory to
standard treatment, intolerant of standard treatment, or for which no standard therapy
exists.
In the dose-expansion phase: histologically- or cytologically-confirmed advanced or
metastatic biliary tract cancer (BTC), esophagus cancer (EC) (squamous cell
carcinoma) or squamous cell carcinoma of the head and neck (SCCHN).
Patients with BTC must have experienced disease progression during or after
receiving at least 1 platinum based palliative therapy for unresectable disease due
to locally advanced, recurrent or metastatic condition.
Patients with EC (squamous cell carcinoma) must have experienced disease
progression during or after receiving at least 1 platinum based palliative therapy
for unresectable disease due to locally advanced, recurrent or metastatic
condition.
Patients with EC who have disease progression within 24 weeks after completion
of multimodality therapy containing platinum, could be enrolled.
Patients with SCCHN must have experienced disease progression during or after
receiving at least 1 platinum based palliative therapy for recurrent or metastatic
disease.
(For Taiwan, We only enroll EC and BTC patients)
4. BTC, EC and SCCHN dose-expansion cohorts: A minimum of 5-10 subjects with
tumoural PD-L1 expression should be enrolled in each cohort.
5. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 and minimum life
expectancy of 16 weeks.
6. Adequate organ and marrow function as defined below:
- Hemoglobin ≥ 9 g/dL
- Absolute neutrophil count ≥ 1,500/mm3
- Platelet count ≥ 100,000/mm3
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ×
institutional upper limit of normal (ULN) or ≤ 5 × ULN for subjects with liver
metastases
- Total bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN for subjects with pancreatic
adenocarcinoma or ≤ 3 × ULN for subjects with documented/suspected Gilbert’s
disease
- Creatinine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation
or by 24-hour urine collection for determination of creatinine clearance (creatinine
clearance by 24-hour urine collection is prioritized if both data is available)
7. Patients must have at least 1 measurable lesion by RECIST v1.1 criteria. Lesion in a
previously irradiated field can be used as measurable disease provided that there has
been clearly demonstrated progression in the lesion.
8. Females of childbearing potential must use 2 methods of effective contraception as
barrier, intrauterine device or hormonal methods (see Table 1) from screening, and
must agree to continue using such precautions for 90 days after the final dose of
investigational product; cessation of birth control after this point should be discussed
with a responsible physician. Periodic abstinence, the rhythm method, and the
withdrawal method are not acceptable methods of birth control.
- Females of childbearing potential are defined as those who are not surgically sterile
(ie, bilateral oophorectomy, bilateral salpingectomy or complete hysterectomy) or
postmenopausal (defined as 12 months with no menses without an alternative
medical cause).
9. Nonsterilized males must use 2 acceptable methods of effective contraception as
barrier, intrauterine device or hormonal methods (see Table 1) from first dose and for
90 days after receipt of the final dose of investigational product.
10. Tumour sample requirements in the dose-escalation phase:
- Available archived tumour tissue sample or fresh biopsy of a lesion that may not be
used for the purpose of tumour assessment (target lesion).
- Tumour sample requirements in the dose-expansion phase:
- Available unstained archived tumour tissue sample in a quantity sufficient to allow
for analysis. Please refer to the Laboratory Manual for details AND
- A recent tumour biopsy (taken following completion of the most recent therapy)
must also be provided. Tumour lesions used for biopsy should not be lesions used
as RECIST target lesions, unless there are no other lesions suitable for biopsy. If a
RECIST target lesion is used for biopsy the lesion must be ≥ 2 cm in longest
diameter. Please refer to the Laboratory Manual for details.
Exclusion Criteria
Exclusion Criteria:
Patients must not enter the study if any of the following exclusion criteria are fulfilled.
1. Treatment with any of the following:
- Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study or the follow-up period of an interventional
study
- Receipt of any immunotherapy, BRAF inhibitor (in melanoma subjects), or
investigational anticancer therapy within 4 weeks prior to the first dose of
MEDI4736; in the case of MAbs, 6 weeks prior to the first dose of MEDI4736
- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for
cancer treatment from study enrollment. Concurrent use of hormones for
non-cancer-related conditions (eg, insulin for diabetes and hormone replacement
therapy) is acceptable. Local treatment of isolated lesions for palliative or curative
intent is acceptable (eg, by local surgery or radiotherapy)
- Current or prior use of immunosuppressive medication within 28 days before the
first dose of MEDI4736, with the exceptions of intranasal and inhaled
corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10
mg/day of prednisolone or equivalent
- Receipt of live attenuated vaccination within 30 days prior to study enrollment or
within 30 days of receiving MEDI4736
- Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
- Major surgical procedure (as defined by the investigator) within 30 days prior to
first dose of MEDI4736 or still recovering from prior surgery
2. Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved
to the National Cancer Institute’s (NCI’s) Common Terminology Criteria for Adverse
Events (CTCAE v4.03) Grade 0 or 1, or to levels dictated in the inclusion/exclusion
criteria with the exception of alopecia and grade 2 peripheral neuropathy
3. Any prior Grade ≥ 3 immune-related adverse event (irAE) while receiving
immunotherapy, including anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4)
treatment or any unresolved irAE Grade ≥ 1
4. Symptomatic or untreated central nervous system (CNS) metastases requiring
concurrent treatment, inclusive of but not limited to surgery, radiation, and/or
corticosteroids
5. Other invasive malignancy within 5 years prior to study enrollment except for
noninvasive malignancies such as cervical carcinoma in situ (CIS), nonmelanomatous
carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that has/have
been surgically cured
6. Female who are pregnant or lactating
7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or
psychiatric illness/social situations that would limit compliance with study
requirement or compromise the ability of the patient to give written informed consent
8. Any condition that, in the opinion of the investigator, would interfere with evaluation
of the investigational product or interpretation of subject safety or study results
9. Active or prior documented autoimmune disease within the past 2 years prior to study
enrollment. Subjects with vitiligo, Grave’s disease or psoriasis not requiring systemic
treatment (within the past 2 years prior to study enrollment) are not excluded.
10. Active or prior documented inflammatory bowel disease (eg, Crohn’s disease,
ulcerative colitis)
11. History of primary immunodeficiency
12. History of organ transplant that requires use of immunosuppressives
13. Known allergy or reaction to any component of the MEDI4736 formulation
14. Known history of tuberculosis
15. Patients who are known to be human immunodeficiency virus (HIV) positive
16. Patients who are positive to hepatitis B surface antigen, anti-hepatitis B core antibody
or anti-hepatitis C antibody
17. Patients must not have more than 50% of the liver parenchyma replaced by tumour
18. Involvement in the planning and conduct of the study (applies to the sponsor staff or
staff at the study site)
Patients must not enter the study if any of the following exclusion criteria are fulfilled.
1. Treatment with any of the following:
- Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study or the follow-up period of an interventional
study
- Receipt of any immunotherapy, BRAF inhibitor (in melanoma subjects), or
investigational anticancer therapy within 4 weeks prior to the first dose of
MEDI4736; in the case of MAbs, 6 weeks prior to the first dose of MEDI4736
- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for
cancer treatment from study enrollment. Concurrent use of hormones for
non-cancer-related conditions (eg, insulin for diabetes and hormone replacement
therapy) is acceptable. Local treatment of isolated lesions for palliative or curative
intent is acceptable (eg, by local surgery or radiotherapy)
- Current or prior use of immunosuppressive medication within 28 days before the
first dose of MEDI4736, with the exceptions of intranasal and inhaled
corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10
mg/day of prednisolone or equivalent
- Receipt of live attenuated vaccination within 30 days prior to study enrollment or
within 30 days of receiving MEDI4736
- Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
- Major surgical procedure (as defined by the investigator) within 30 days prior to
first dose of MEDI4736 or still recovering from prior surgery
2. Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved
to the National Cancer Institute’s (NCI’s) Common Terminology Criteria for Adverse
Events (CTCAE v4.03) Grade 0 or 1, or to levels dictated in the inclusion/exclusion
criteria with the exception of alopecia and grade 2 peripheral neuropathy
3. Any prior Grade ≥ 3 immune-related adverse event (irAE) while receiving
immunotherapy, including anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4)
treatment or any unresolved irAE Grade ≥ 1
4. Symptomatic or untreated central nervous system (CNS) metastases requiring
concurrent treatment, inclusive of but not limited to surgery, radiation, and/or
corticosteroids
5. Other invasive malignancy within 5 years prior to study enrollment except for
noninvasive malignancies such as cervical carcinoma in situ (CIS), nonmelanomatous
carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that has/have
been surgically cured
6. Female who are pregnant or lactating
7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or
psychiatric illness/social situations that would limit compliance with study
requirement or compromise the ability of the patient to give written informed consent
8. Any condition that, in the opinion of the investigator, would interfere with evaluation
of the investigational product or interpretation of subject safety or study results
9. Active or prior documented autoimmune disease within the past 2 years prior to study
enrollment. Subjects with vitiligo, Grave’s disease or psoriasis not requiring systemic
treatment (within the past 2 years prior to study enrollment) are not excluded.
10. Active or prior documented inflammatory bowel disease (eg, Crohn’s disease,
ulcerative colitis)
11. History of primary immunodeficiency
12. History of organ transplant that requires use of immunosuppressives
13. Known allergy or reaction to any component of the MEDI4736 formulation
14. Known history of tuberculosis
15. Patients who are known to be human immunodeficiency virus (HIV) positive
16. Patients who are positive to hepatitis B surface antigen, anti-hepatitis B core antibody
or anti-hepatitis C antibody
17. Patients must not have more than 50% of the liver parenchyma replaced by tumour
18. Involvement in the planning and conduct of the study (applies to the sponsor staff or
staff at the study site)
The Estimated Number of Participants
-
Taiwan
40 participants
-
Global
204 participants
