Clinical Trials List
Protocol NumberD5165C00001
NCT Number(ClinicalTrials.gov Identfier)NCT02454933
Completed
2015-07-01 - 2019-07-31
Phase III
Terminated4
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
ICD-9162.0
Malignant neoplasm of trachea
A Phase III, Multi-Centre, Open Label, Randomized Study to Assess the Efficacy and Safety of AZD9291 in Combination with MEDI4736 versus AZD9291 Monotherapy in Patients with Locally Advanced or Metastatic Epidermal Growth Factor Receptor T790M mutation-positive Non-Small Cell Lung Cancer who have received Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy (CAURAL)
-
Trial Applicant
-
Sponsor
AstraZeneca
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- KUO-HSUAN HSU Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
- TSUNG -YING YANG Division of Thoracic Medicine
- 陳焜結 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 鄭裕仁 Division of Thoracic Surgery
- 李和昇 Division of Thoracic Medicine
- 謝坤洲 Division of Thoracic Surgery
- 邱建通 Division of Thoracic Medicine
- 陳鍾岳 Division of Thoracic Medicine
- 吳俊廷 Division of Thoracic Medicine
- 胡釋文 Division of Thoracic Medicine
- 許棨逵 Division of Thoracic Medicine
- 陳俊榮 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Jih-Hsiang Lee Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- Chong-Jen Yu Division of General Internal Medicine
- 廖唯昱 Division of General Internal Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- JIN-YUAN SHIH Division of General Internal Medicine
- 林宗哲 Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- 陳冠宇 Division of General Internal Medicine
- 許嘉林 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Non-Small Cell Lung Cancer
Objectives
Primary objectives
To assess the efficacy of AZD9291 in combination with MEDI4736 versus AZD9291 monotherapy
in terms of PFS as 2nd line or higher treatment for patients who have progressed following an
approved EGFR-TKI therapy.
Secondary objectives
ü To further assess the efficacy of AZD9291 in combination with MEDI4736 versus AZD9291
monotherapy in terms of:
- Objective Response Rate (ORR)
- Duration of Response (DoR)
- Disease Control Rate (DCR)
- Tumour shrinkage
- Overall Survival (OS)
- PFS landmark analyses
· To assess the impact of AZD9291 in combination with MEDI4736 versus AZD9291
monotherapy on disease-related symptoms and health-related QoL in NSCLC patients.
· To assess the PK of AZD9291 as a single agent and in combination with MEDI4736.
ü To characterise the PK, immunogenicity and pharmacodynamics of MEDI4736 after single
dosing and at steady state after multiple dosing when given intravenously to patients with
EGFRm NSCLC in combination with AZD9291.
ü To assess the safety and tolerability profile of AZD9291 as a single agent and in combination
with MEDI4736.
Test Drug
AZD9291 / MEDI4736
Active Ingredient
AZD9291
MEDI4736
MEDI4736
Dosage Form
tablet
Infusion
Infusion
Dosage
40; 80
50
50
Endpoints
1. Primary efficacy variable:
ü Progression Free Survival (PFS) by Investigator assessments according to RECIST 1.1.
ü Sensitivity analysis of PFS by Blinded Independent Central Review (BICR) according to
RECIST 1.1.
2. Secondary efficacy variables:
ü ORR, DoR, DCR and tumour shrinkage using Investigator assessments according to
RECIST 1.1
- Analysis of OS
- OS landmark analysis (at 12 and 24 months)
- PFS landmark analysis (at 6, 12 and 24 months)
- Sensitivity analyses for ORR, DoR, DCR and tumour shrinkage using BICR assessments
according to RECIST 1.1
ü EORTC QLQ-C30: Questionnaire consisting of 30 items measuring patients general
cancer symptoms and functioning.
ü EORTC QLQ LC13: A complementary questionnaire measuring lung cancer symptoms
and side-effects from conventional chemo- and radiotherapy.
ü QLQ-LC13 and C30 will be administered via handheld electronic device.
ü Plasma concentrations of AZD9291 and metabolites AZ5104 and AZ7550.
ü Plasma concentrations of MEDI4736 to characterize PK.
ü Blood samples for soluble PD-L1 and ADA are also obtained to characterize
pharmacodynamics and immunogenicity, respectively.
ü Adverse events (graded by Common Terminology Criteria for Adverse Event (CTCAE v4)
- Clinical chemistry, haematology and urinalysis
- Vital signs (pulse and blood pressure), Physical Examination, Weight
- Centrally reviewed digital Electrocardiogram (ECG)
- Echocardiogram/ Multi Gated Acquisition Scan (MUGA) (for Left Ventricular Ejection
Fraction)
- WHO Performance Status
ü Progression Free Survival (PFS) by Investigator assessments according to RECIST 1.1.
ü Sensitivity analysis of PFS by Blinded Independent Central Review (BICR) according to
RECIST 1.1.
2. Secondary efficacy variables:
ü ORR, DoR, DCR and tumour shrinkage using Investigator assessments according to
RECIST 1.1
- Analysis of OS
- OS landmark analysis (at 12 and 24 months)
- PFS landmark analysis (at 6, 12 and 24 months)
- Sensitivity analyses for ORR, DoR, DCR and tumour shrinkage using BICR assessments
according to RECIST 1.1
ü EORTC QLQ-C30: Questionnaire consisting of 30 items measuring patients general
cancer symptoms and functioning.
ü EORTC QLQ LC13: A complementary questionnaire measuring lung cancer symptoms
and side-effects from conventional chemo- and radiotherapy.
ü QLQ-LC13 and C30 will be administered via handheld electronic device.
ü Plasma concentrations of AZD9291 and metabolites AZ5104 and AZ7550.
ü Plasma concentrations of MEDI4736 to characterize PK.
ü Blood samples for soluble PD-L1 and ADA are also obtained to characterize
pharmacodynamics and immunogenicity, respectively.
ü Adverse events (graded by Common Terminology Criteria for Adverse Event (CTCAE v4)
- Clinical chemistry, haematology and urinalysis
- Vital signs (pulse and blood pressure), Physical Examination, Weight
- Centrally reviewed digital Electrocardiogram (ECG)
- Echocardiogram/ Multi Gated Acquisition Scan (MUGA) (for Left Ventricular Ejection
Fraction)
- WHO Performance Status
Inclution Criteria
u Inclusion criteria:
For inclusion in the study patients should fulfil the following criteria:
1. Provision of informed consent prior to any study specific procedures, sampling and analyses.
If a patient declines to participate in any voluntary exploratory research and/or genetic
component of the study, there will be no penalty or loss of benefit to the patient and he/she will
not be excluded from other aspects of the study.
2. Male or female aged at least 18 years and older. Patients from Japan and Taiwan should be
aged at least 20 years.
3. Histological or cytological confirmation diagnosis of NSCLC.
4. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy
5. Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be
associated with EGFR-TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).
6. Radiological documentation of disease progression while on a previous continuous treatment
with an approved EGFR-TKI (eg, gefitinib, erlotinib or afatinib). In addition other lines of
therapy may have been given. All patients must have documented radiological progression on
the last treatment administered prior to enrolling in the study.
7. Patients must have central lab confirmation of tumour T790M status from a biopsy taken after
disease progression on the most recent treatment regimen. Only patients with a T790M positive
status central test result will be included in the study, see Section 4.1.
8. At least one lesion, not previously irradiated, and not biopsied during the screening period, that
can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes
which must have short axis ≥ 15 mm) with computerised tomography (CT) or magnetic
resonance imaging (MRI) which is suitable for accurate repeated measurements per RECIST
v1.1 guidelines. If only one measurable lesion exists, it is acceptable to be used as long as it
has not been previously irradiated and baseline tumour assessment scans are done at least
14 days after the screening biopsy is performed.
9. World Health Organisation (WHO) performance status 0-1 with no deterioration over the
previous 2 weeks and minimum life expectancy of 12 weeks.
10. Females should be using adequate contraceptive measures, should not be breast feeding and
must have a negative pregnancy test prior to start of dosing (if of child-bearing potential) or
must have evidence of non-child-bearing potential by fulfilling one of the following criteria at
screening:
- Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12
months following cessation of all exogenous hormonal treatments
- Women under 50 years old would be consider postmenopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and with LH and FSH levels in the post-menopausal range for the institution
Documentation of irreversible surgical sterilisation by hysterectomy, bilateral
oophorectomy or bilateral salpingectomy but not tubal ligation
11. Male patients should be willing to use barrier contraception (see Restrictions, Section 3.6).
12. For inclusion in the optional genetic research: Patients must provide informed consent for
genetic research. If a patient declines to participate in any voluntary exploratory research
and/or genetic component of the study, there will be no penalty or loss of benefit to the patient
and he/she will not be excluded from other aspects of the study
For inclusion in the study patients should fulfil the following criteria:
1. Provision of informed consent prior to any study specific procedures, sampling and analyses.
If a patient declines to participate in any voluntary exploratory research and/or genetic
component of the study, there will be no penalty or loss of benefit to the patient and he/she will
not be excluded from other aspects of the study.
2. Male or female aged at least 18 years and older. Patients from Japan and Taiwan should be
aged at least 20 years.
3. Histological or cytological confirmation diagnosis of NSCLC.
4. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy
5. Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be
associated with EGFR-TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).
6. Radiological documentation of disease progression while on a previous continuous treatment
with an approved EGFR-TKI (eg, gefitinib, erlotinib or afatinib). In addition other lines of
therapy may have been given. All patients must have documented radiological progression on
the last treatment administered prior to enrolling in the study.
7. Patients must have central lab confirmation of tumour T790M status from a biopsy taken after
disease progression on the most recent treatment regimen. Only patients with a T790M positive
status central test result will be included in the study, see Section 4.1.
8. At least one lesion, not previously irradiated, and not biopsied during the screening period, that
can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes
which must have short axis ≥ 15 mm) with computerised tomography (CT) or magnetic
resonance imaging (MRI) which is suitable for accurate repeated measurements per RECIST
v1.1 guidelines. If only one measurable lesion exists, it is acceptable to be used as long as it
has not been previously irradiated and baseline tumour assessment scans are done at least
14 days after the screening biopsy is performed.
9. World Health Organisation (WHO) performance status 0-1 with no deterioration over the
previous 2 weeks and minimum life expectancy of 12 weeks.
10. Females should be using adequate contraceptive measures, should not be breast feeding and
must have a negative pregnancy test prior to start of dosing (if of child-bearing potential) or
must have evidence of non-child-bearing potential by fulfilling one of the following criteria at
screening:
- Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12
months following cessation of all exogenous hormonal treatments
- Women under 50 years old would be consider postmenopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and with LH and FSH levels in the post-menopausal range for the institution
Documentation of irreversible surgical sterilisation by hysterectomy, bilateral
oophorectomy or bilateral salpingectomy but not tubal ligation
11. Male patients should be willing to use barrier contraception (see Restrictions, Section 3.6).
12. For inclusion in the optional genetic research: Patients must provide informed consent for
genetic research. If a patient declines to participate in any voluntary exploratory research
and/or genetic component of the study, there will be no penalty or loss of benefit to the patient
and he/she will not be excluded from other aspects of the study
Exclusion Criteria
u Exclusion criteria:
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff
and/or staff at the study site).
2. Intervention with any of the following:
- Treatment with an EGFR-TKI within approximately 5x half-life (eg, within 8 days for
erlotinib, gefitinib or afatanib, within 10 days for dacomitinib) of the first dose of study
treatment. If sufficient washout time has not occurred due to schedule or PK properties,
an alternative appropriate washout time based on known duration and time to
reversibility of drug related adverse events could be agreed upon by AstraZeneca and the
Investigator.
- Any cytotoxic chemotherapy, investigational agents or other anticancer drugs for the
treatment of advanced NSCLC from a previous treatment regimen or clinical study within
14 days of the first dose of study treatment.
- Patients currently receiving (or unable to stop use at least 1 week (3 weeks for inducers)
prior to receiving the first dose of AZD9291) medications or herbal supplements known
to be potent inhibitors or inducers of CYP3A4 (Appendix F).
- Previous treatment with AZD9291 or other agents specifically targeted against EGFR
T790M mutation positive NSCLC (eg rociletinib [CO-1686]).
- Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months of starting
1st EGFR-TKI treatment.
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
radiation within 4 weeks of randomization. Radiotherapy with a limited field of
radiation for palliation >1 week of the first dose of study treatment is allowed.
- Major surgical procedure, (excluding placement of vascular access) or significant
traumatic injury within 4 weeks of the first dose of study treatment, or have an
anticipated need for major surgery during the study.
- No prior exposure to immune-mediated therapy including, but not limited to, other anti
CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2)
antibodies, excluding therapeutic anticancer vaccines.
3. Current or prior use of immunosuppressive medication within 14 days before the first dose of
MEDI4736. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular
injection).
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or
its equivalent
- Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
4. With the exception of alopecia and grade 2 prior platinum-therapy related neuropathy, any
unresolved toxicities from prior therapy and/or pre-study biopsies greater than CTCAE grade 1 at
the time of starting study treatment.
5. History of active primary immunodeficiency.
6. Current leptomeningeal metastases or spinal cord compression. Brain metastases are only
permitted if asymptomatic and stable (not requiring steroids for at least 4 weeks prior to start of
study treatment).
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, active bleeding diatheses including
any patient known to have evidence of acute hepatitis B, hepatitis C or human immunodeficiency
virus (HIV), or psychiatric illness/social situations that would limit compliance with study
requirements or compromise the ability of the patient to give written informed consent.
8. Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTcF) > 470 msec obtained from 3 ECG readings
- Any clinically important abnormalities in rhythm, conduction or morphology of resting
ECG eg, complete left bundle branch block, third degree heart block, second degree heart
block, PR interval >250msec.
- Any factors that increase the risk of QTcF prolongation or risk of arrhythmic events such
as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT
syndrome or unexplained sudden death under 40 years of age in first degree relatives or
any concomitant medication known to prolong the QT interval.
9. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the
formulated product or previous significant bowel resection that would preclude adequate
absorption of AZD9291
10. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation
pneumonitis which required steroid treatment, or any evidence of clinically active interstitial
lung disease.
11. History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease ≥5 years before
the first dose of study drug and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of
disease
- Adequately treated carcinoma in situ without evidence of disease (eg, cervical cancer in
situ)
12. Active or prior documented autoimmune or inflammatory disorders (including inflammatory
bowel disease [eg, colitis or Crohn’s disease], diverticulitis with the exception of diverticulosis,
celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea),
systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis
with polyangiitis), Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc) within the
past 3 years prior to the start of treatment.
The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone
replacement or psoriasis not requiring systemic treatment
13. History of organ transplant that requires use of immunosuppressive medications including, but
not limited to systemic corticosteroids at doses beyond 10 mg/day of prednisone or equivalent,
methotrexate, azathioprine and tumour necrosis factor alpha (TNF-α) blockers. Use of
immunosuppressive medications for the management of investigational product-related AEs is
acceptable. In addition, use of inhaled and intranasal corticosteroids is permitted.
14. Known history of clinical diagnosis of tuberculosis
15. Receipt of live, attenuated vaccine within 30 days prior to the first dose of MEDI4736.
16. History of hypersensitivity to active or inactive excipients of AZD9291 or MEDI4736 or drugs
with a similar chemical structure or class to these agents.
17. Judgment by the Investigator that the patient should not participate in the study if the patient is
unlikely to comply with study procedures, restrictions and requirements.
18. Women who are breast feeding.
19. Inadequate bone marrow reserve or organ function as demonstrated by any of the following
laboratory values:
- Absolute neutrophil count < 1.5 x 109
/L
- Platelet count < 100 x 109
/L
- Haemoglobin < 90 g/L
- Alanine aminotransferase > 2.5 times the upper limit of normal (ULN) if no demonstrable
liver metastases or > 5 times ULN in the presence of liver metastases
- Aspartate aminotransferase > 2.5 times ULN if no demonstrable liver metastases or > 5
times ULN in the presence of liver metastases
- Total bilirubin > 1.5 times ULN. Total bilirubin >3 times the ULN in patients with
documented Gilbert’s Syndrome (unconjugated hyperbilirubinaemia) or in the presence
of liver metastases
- Creatinine >1.5 times ULN concurrent with creatinine clearance < 50 ml/min (measured
or calculated by Cockcroft and Gault equation), confirmation of creatinine clearance is
only required when creatinine is > 1.5 times ULN.
In addition, the following is considered a criterion for exclusion from the exploratory genetic
research:
20. Previous allogeneic bone marrow transplant.
21. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic
sample collection.
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff
and/or staff at the study site).
2. Intervention with any of the following:
- Treatment with an EGFR-TKI within approximately 5x half-life (eg, within 8 days for
erlotinib, gefitinib or afatanib, within 10 days for dacomitinib) of the first dose of study
treatment. If sufficient washout time has not occurred due to schedule or PK properties,
an alternative appropriate washout time based on known duration and time to
reversibility of drug related adverse events could be agreed upon by AstraZeneca and the
Investigator.
- Any cytotoxic chemotherapy, investigational agents or other anticancer drugs for the
treatment of advanced NSCLC from a previous treatment regimen or clinical study within
14 days of the first dose of study treatment.
- Patients currently receiving (or unable to stop use at least 1 week (3 weeks for inducers)
prior to receiving the first dose of AZD9291) medications or herbal supplements known
to be potent inhibitors or inducers of CYP3A4 (Appendix F).
- Previous treatment with AZD9291 or other agents specifically targeted against EGFR
T790M mutation positive NSCLC (eg rociletinib [CO-1686]).
- Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months of starting
1st EGFR-TKI treatment.
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
radiation within 4 weeks of randomization. Radiotherapy with a limited field of
radiation for palliation >1 week of the first dose of study treatment is allowed.
- Major surgical procedure, (excluding placement of vascular access) or significant
traumatic injury within 4 weeks of the first dose of study treatment, or have an
anticipated need for major surgery during the study.
- No prior exposure to immune-mediated therapy including, but not limited to, other anti
CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2)
antibodies, excluding therapeutic anticancer vaccines.
3. Current or prior use of immunosuppressive medication within 14 days before the first dose of
MEDI4736. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular
injection).
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or
its equivalent
- Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
4. With the exception of alopecia and grade 2 prior platinum-therapy related neuropathy, any
unresolved toxicities from prior therapy and/or pre-study biopsies greater than CTCAE grade 1 at
the time of starting study treatment.
5. History of active primary immunodeficiency.
6. Current leptomeningeal metastases or spinal cord compression. Brain metastases are only
permitted if asymptomatic and stable (not requiring steroids for at least 4 weeks prior to start of
study treatment).
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, active bleeding diatheses including
any patient known to have evidence of acute hepatitis B, hepatitis C or human immunodeficiency
virus (HIV), or psychiatric illness/social situations that would limit compliance with study
requirements or compromise the ability of the patient to give written informed consent.
8. Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTcF) > 470 msec obtained from 3 ECG readings
- Any clinically important abnormalities in rhythm, conduction or morphology of resting
ECG eg, complete left bundle branch block, third degree heart block, second degree heart
block, PR interval >250msec.
- Any factors that increase the risk of QTcF prolongation or risk of arrhythmic events such
as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT
syndrome or unexplained sudden death under 40 years of age in first degree relatives or
any concomitant medication known to prolong the QT interval.
9. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the
formulated product or previous significant bowel resection that would preclude adequate
absorption of AZD9291
10. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation
pneumonitis which required steroid treatment, or any evidence of clinically active interstitial
lung disease.
11. History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease ≥5 years before
the first dose of study drug and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of
disease
- Adequately treated carcinoma in situ without evidence of disease (eg, cervical cancer in
situ)
12. Active or prior documented autoimmune or inflammatory disorders (including inflammatory
bowel disease [eg, colitis or Crohn’s disease], diverticulitis with the exception of diverticulosis,
celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea),
systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis
with polyangiitis), Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc) within the
past 3 years prior to the start of treatment.
The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone
replacement or psoriasis not requiring systemic treatment
13. History of organ transplant that requires use of immunosuppressive medications including, but
not limited to systemic corticosteroids at doses beyond 10 mg/day of prednisone or equivalent,
methotrexate, azathioprine and tumour necrosis factor alpha (TNF-α) blockers. Use of
immunosuppressive medications for the management of investigational product-related AEs is
acceptable. In addition, use of inhaled and intranasal corticosteroids is permitted.
14. Known history of clinical diagnosis of tuberculosis
15. Receipt of live, attenuated vaccine within 30 days prior to the first dose of MEDI4736.
16. History of hypersensitivity to active or inactive excipients of AZD9291 or MEDI4736 or drugs
with a similar chemical structure or class to these agents.
17. Judgment by the Investigator that the patient should not participate in the study if the patient is
unlikely to comply with study procedures, restrictions and requirements.
18. Women who are breast feeding.
19. Inadequate bone marrow reserve or organ function as demonstrated by any of the following
laboratory values:
- Absolute neutrophil count < 1.5 x 109
/L
- Platelet count < 100 x 109
/L
- Haemoglobin < 90 g/L
- Alanine aminotransferase > 2.5 times the upper limit of normal (ULN) if no demonstrable
liver metastases or > 5 times ULN in the presence of liver metastases
- Aspartate aminotransferase > 2.5 times ULN if no demonstrable liver metastases or > 5
times ULN in the presence of liver metastases
- Total bilirubin > 1.5 times ULN. Total bilirubin >3 times the ULN in patients with
documented Gilbert’s Syndrome (unconjugated hyperbilirubinaemia) or in the presence
of liver metastases
- Creatinine >1.5 times ULN concurrent with creatinine clearance < 50 ml/min (measured
or calculated by Cockcroft and Gault equation), confirmation of creatinine clearance is
only required when creatinine is > 1.5 times ULN.
In addition, the following is considered a criterion for exclusion from the exploratory genetic
research:
20. Previous allogeneic bone marrow transplant.
21. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic
sample collection.
The Estimated Number of Participants
-
Taiwan
80 participants
-
Global
880 participants
