Clinical Trials List
Protocol NumberD419LC00001
NCT Number(ClinicalTrials.gov Identfier)NCT02551159
2015-10-22 - 2019-12-31
Phase III
Terminated7
ICD-10C44.42
Squamous cell carcinoma of skin of scalp and neck
A Phase III Randomized, Open-label, Multi-center, Global Study of MEDI4736 in Combination with Tremelimumab versus Standard of Care in the Treatment of First-line Recurrent or Metastatic Squamous Cell Head and Neck Cancer Patients
-
Trial Applicant
-
Sponsor
AstraZeneca
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 蔡牧宏 Division of Hematology & Oncology
- Sen-Tien Tsai Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 朱本元 Division of Otolaryngology
- Sheng-Yu Chen Division of Otolaryngology
- Chun-Yu Liu Division of Otolaryngology
- 陳盛裕 未分科
- 戴世光 Division of Otolaryngology
- Mu-Hsin Chang Division of Otolaryngology
The Actual Total Number of Participants Enrolled
2 Terminated
Audit
None
Co-Principal Investigator
- 林偉哲 Division of Radiology
- Meng-Jer Hsieh Division of Hematology & Oncology
- 方富民 Division of Radiation Therapy
- 陳彥豪 Division of Hematology & Oncology
- Tai-Jan Chiu Division of Hematology & Oncology
- Shau-Hsuan Li Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Ching-Chan Lin Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- 廖斌志 Division of Otolaryngology
- Hsiang-Fong Kao Division of Otolaryngology
- HUAI-CHENG HUANG Division of Otolaryngology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Squamous Cell Head and Neck Cancer
Objectives
Primary objectives
To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in
terms of PFS and OS
Secondary objectives
To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to
SoC in terms of PFS, ORR, DoR, APF12, PFS2, OS, and OS24
To assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of PFS, ORR,
PFS2, OS, and OS24
To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to
MEDI4736 monotherapy in terms of PFS, ORR, and OS
To assess disease-related symptoms and health-related quality of life in patients treated with
MEDI4736 + tremelimumab combination therapy compared to SoC using the European
Organisation for Research and Treatment of Cancer (EORTC) 30-item Core Quality of Life
Questionnaire (QLQ-C30) version 3 and the 35-item Head and Neck Quality of Life
Questionnaire (QLQ-H&N35) module
To assess the PK of MEDI4736 + tremelimumab combination therapy and MEDI4736
monotherapy
To investigate the immunogenicity of MEDI4736 and tremelimumab
Safety objectives
To assess the safety and tolerability profile of MEDI4736 + tremelimumab combination therapy
and MEDI4736 monotherapy compared to SoC in the first-line setting for treatment of SCCHN
Test Drug
MEDI4736; Tremelimumab
Active Ingredient
MEDI4736
Tremelimumab
Tremelimumab
Dosage Form
Injection
Dosage
50
20
20
Endpoints
1. Primary efficacy variable:
PFS using the Investigator’s assessments according to RECIST 1.1
OS
2. Secondary efficacy variables:
PFS and ORR in patients with PD-L1-negative SCCHN using Investigator assessments
according to RECIST 1.1
OS in patients with PD-L1-negative SCCHN
PFS, ORR, DoR, and APF12 using Investigator assessments according to RECIST 1.1
PFS2 using local standard clinical practice
OS and OS24
EORTC QLQ-C30
EORTC QLQ-H&N35
Changes in World Health Organization/Eastern Cooperative Oncology Group performance
status
Concentration of MEDI4736 and tremelimumab in blood and non-compartmental PK
parameters, such as peak concentration and trough (as data allow; sparse sampling)
Presence of ADAs for MEDI4736 and tremelimumab
3. Safety variables:
Adverse events, physical examinations, laboratory findings (including clinical chemistry,
hematology, and urinalysis), vital signs (including blood pressure and pulse), and
electrocardiograms
PFS using the Investigator’s assessments according to RECIST 1.1
OS
2. Secondary efficacy variables:
PFS and ORR in patients with PD-L1-negative SCCHN using Investigator assessments
according to RECIST 1.1
OS in patients with PD-L1-negative SCCHN
PFS, ORR, DoR, and APF12 using Investigator assessments according to RECIST 1.1
PFS2 using local standard clinical practice
OS and OS24
EORTC QLQ-C30
EORTC QLQ-H&N35
Changes in World Health Organization/Eastern Cooperative Oncology Group performance
status
Concentration of MEDI4736 and tremelimumab in blood and non-compartmental PK
parameters, such as peak concentration and trough (as data allow; sparse sampling)
Presence of ADAs for MEDI4736 and tremelimumab
3. Safety variables:
Adverse events, physical examinations, laboratory findings (including clinical chemistry,
hematology, and urinalysis), vital signs (including blood pressure and pulse), and
electrocardiograms
Inclution Criteria
Inclusion criteria:
Study procedures obtained prior to informed consent for other purposes may be used for screening if
the patient/legal representative consents to allow use of these procedures for screening purposes.
For inclusion in the study patients should fulfill the following criteria:
1. Age ≥18 years at the time of screening (≧20 years in Taiwan)
2. Written informed consent and any locally required authorization (eg, Health Insurance
Portability and Accountability Act in the United States, European Union [EU] Data Privacy
Directive in the EU) obtained from the patient/legal representative prior to performing any
protocol-related procedures, including screening evaluations. (For patients aged <20 years and
enrolling in Japan, a written informed consent should be obtained from the patient and his or
her legally acceptable representative.)
3. Histologically confirmed recurrent or metastatic SCCHN (oral cavity, oropharynx,
hypopharynx, or larynx) not amenable to local curative therapy with surgery or radiation
therapy.
4. No prior systemic chemotherapy for recurrent or metastatic disease
5. Able and willing to give valid written consent to undergo a fresh tumor biopsy for the purpose
of screening for this clinical trial or to provide an available archival tumor sample taken <3
months ago if a fresh tumor biopsy is not feasible with an acceptable clinical risk. Tumor
lesions used for fresh biopsies should not be the same lesions used as RECIST target lesions,
unless there are no other lesions suitable for biopsy.
6. For patients with OPC only: confirmed HPV status by p16 IHC prior to randomization.
7. Confirmed PD-L1–positive or –negative SCCHN by the Ventana IHC assay
- On a recent sample (<3 months) or fresh tumor biopsy
- Regardless of the age of the test result, if the patient’s PD-L1 status has already been
assessed using the Ventana assay as a part of the screening process for another
AstraZeneca/MedImmune study, this test result can be used for the determination of
eligibility, provided no intervening therapy has been administered.
- Note: A positive PD-L1 sample is measured using a defined cut-off based on ≥25% of
tumor cells with membrane staining of any intensity for PD-L1. A negative PD-L1 sample is
determined by 0% to 24% of tumor cells with membrane staining for PD-L1.
8. World Health Organization (WHO)/ECOG performance status of 0 or 1 at enrollment
9. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10
mm in the longest diameter (except lymph nodes, which must have a short axis ≥15 mm) with
CT or MRI and that is suitable for accurate repeated measurements as per RECIST 1.1
guidelines. Lesions in a previously irradiated field can be used as measurable disease provided
that there has been demonstrated progression in the lesion and the lesion measures at least 20
mm.
10. Patients must have no prior exposure to immune-mediated therapy, including anti-CTLA-4,
anti-PD-1, anti–PD-L1, or anti–programmed cell death ligand 2 antibodies, excluding
therapeutic anticancer vaccines. Exposure to other investigational agents may be permitted after
discussion with the Sponsor.
11. Adequate organ and marrow function independent of transfusion for at least 7 days prior to
screening and independent of growth factor support for at least 14 days prior to screening,
defined as follows:
- Hemoglobin ≥9 g/dL
- Absolute neutrophil count ≥1500/mm3
- Platelet count ≥100000/mm3
- Serum bilirubin ≤1.5 × the upper limit of normal (ULN). This will not apply to patients with
confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia [predominantly
unconjugated bilirubin] in the absence of evidence of hemolysis or hepatic pathology), who
will be allowed in consultation with their physician.
- ALT and AST ≤2.5 × ULN; for patients with hepatic metastases, ALT and AST ≤5 × ULN
- Calculated creatinine clearance >40 mL/min as determined by Cockcroft-Gault (using actual
body weight) (creatinine clearance of 50 mL/min is needed if cisplatin is used)
Males:
Creatinine Clearance = Weight (kg) × (140 – Age)
(mL/min) 72 × serum creatinine (mg/dL)
Females:
Creatinine Clearance = Weight (kg) × (140 – Age) × 0.85
(mL/min) 72 × serum creatinine (mg/dL)
12. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female
pre-menopausal patients. Women will be considered post-menopausal if they have been
amenorrheic for 12 months without an alternative medical cause. The following age-specific
requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal treatments
and if they have luteinizing hormone and folliclestimulating hormone levels in the
post-menopausal range for the institution.
- Women ≥50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced oophorectomy with last menses >1 year ago, had
chemotherapy-induced menopause with >1 year interval since last menses, or underwent
surgical sterilization (bilateral oophorectomy or hysterectomy).
Criteria for continuation of treatment in the setting of progressive disease
For all patients who are treated through progression at the Investigator’s discretion, the Investigator
should ensure that patients still meet all of the inclusion criteria and none of the exclusion criteria for
this study, and that patients meet the following specific criteria for treatment in the setting of PD:
1. Written informed consent to continue treatment or retreatment in the setting of PD. This
consent document will specify that treatment beyond initial evidence of PD is not the
“standard-of-care” and that alternative treatment options, either locally licensed treatments or
other clinical trials, are available for this patient population.
2. Absence of clinical symptoms or signs indicating clinically significant disease progression
3. No decline in WHO/ECOG performance status to >1
4. Absence of rapid disease progression or threat to vital organs or critical anatomical sites (eg,
central nervous system metastasis, respiratory failure due to tumor compression, or spinal cord
compression) requiring urgent alternative medical intervention
The IP should be discontinued if there is confirmed PD while receiving IMT following a
previous response (CR or PR) to the IP in the target lesions (ie, the response and progression
events both occurred in the target lesions while receiving the IP during the treatment period).
Criteria for retreatment in the MEDI4736 + tremelimumab arm
Patients in the MEDI4736 + tremelimumab combination therapy arm are eligible to receive
retreatment with the MEDI4736 + tremelimumab combination therapy provided progression
occurred in the monotherapy portion of dosing and the patient meets all the criteria specified above
for treatment beyond confirmed progression. Patients who discontinue treatment in 1 treatment arm
may not switch to treatment in a different group.
Study procedures obtained prior to informed consent for other purposes may be used for screening if
the patient/legal representative consents to allow use of these procedures for screening purposes.
For inclusion in the study patients should fulfill the following criteria:
1. Age ≥18 years at the time of screening (≧20 years in Taiwan)
2. Written informed consent and any locally required authorization (eg, Health Insurance
Portability and Accountability Act in the United States, European Union [EU] Data Privacy
Directive in the EU) obtained from the patient/legal representative prior to performing any
protocol-related procedures, including screening evaluations. (For patients aged <20 years and
enrolling in Japan, a written informed consent should be obtained from the patient and his or
her legally acceptable representative.)
3. Histologically confirmed recurrent or metastatic SCCHN (oral cavity, oropharynx,
hypopharynx, or larynx) not amenable to local curative therapy with surgery or radiation
therapy.
4. No prior systemic chemotherapy for recurrent or metastatic disease
5. Able and willing to give valid written consent to undergo a fresh tumor biopsy for the purpose
of screening for this clinical trial or to provide an available archival tumor sample taken <3
months ago if a fresh tumor biopsy is not feasible with an acceptable clinical risk. Tumor
lesions used for fresh biopsies should not be the same lesions used as RECIST target lesions,
unless there are no other lesions suitable for biopsy.
6. For patients with OPC only: confirmed HPV status by p16 IHC prior to randomization.
7. Confirmed PD-L1–positive or –negative SCCHN by the Ventana IHC assay
- On a recent sample (<3 months) or fresh tumor biopsy
- Regardless of the age of the test result, if the patient’s PD-L1 status has already been
assessed using the Ventana assay as a part of the screening process for another
AstraZeneca/MedImmune study, this test result can be used for the determination of
eligibility, provided no intervening therapy has been administered.
- Note: A positive PD-L1 sample is measured using a defined cut-off based on ≥25% of
tumor cells with membrane staining of any intensity for PD-L1. A negative PD-L1 sample is
determined by 0% to 24% of tumor cells with membrane staining for PD-L1.
8. World Health Organization (WHO)/ECOG performance status of 0 or 1 at enrollment
9. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10
mm in the longest diameter (except lymph nodes, which must have a short axis ≥15 mm) with
CT or MRI and that is suitable for accurate repeated measurements as per RECIST 1.1
guidelines. Lesions in a previously irradiated field can be used as measurable disease provided
that there has been demonstrated progression in the lesion and the lesion measures at least 20
mm.
10. Patients must have no prior exposure to immune-mediated therapy, including anti-CTLA-4,
anti-PD-1, anti–PD-L1, or anti–programmed cell death ligand 2 antibodies, excluding
therapeutic anticancer vaccines. Exposure to other investigational agents may be permitted after
discussion with the Sponsor.
11. Adequate organ and marrow function independent of transfusion for at least 7 days prior to
screening and independent of growth factor support for at least 14 days prior to screening,
defined as follows:
- Hemoglobin ≥9 g/dL
- Absolute neutrophil count ≥1500/mm3
- Platelet count ≥100000/mm3
- Serum bilirubin ≤1.5 × the upper limit of normal (ULN). This will not apply to patients with
confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia [predominantly
unconjugated bilirubin] in the absence of evidence of hemolysis or hepatic pathology), who
will be allowed in consultation with their physician.
- ALT and AST ≤2.5 × ULN; for patients with hepatic metastases, ALT and AST ≤5 × ULN
- Calculated creatinine clearance >40 mL/min as determined by Cockcroft-Gault (using actual
body weight) (creatinine clearance of 50 mL/min is needed if cisplatin is used)
Males:
Creatinine Clearance = Weight (kg) × (140 – Age)
(mL/min) 72 × serum creatinine (mg/dL)
Females:
Creatinine Clearance = Weight (kg) × (140 – Age) × 0.85
(mL/min) 72 × serum creatinine (mg/dL)
12. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female
pre-menopausal patients. Women will be considered post-menopausal if they have been
amenorrheic for 12 months without an alternative medical cause. The following age-specific
requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal treatments
and if they have luteinizing hormone and folliclestimulating hormone levels in the
post-menopausal range for the institution.
- Women ≥50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced oophorectomy with last menses >1 year ago, had
chemotherapy-induced menopause with >1 year interval since last menses, or underwent
surgical sterilization (bilateral oophorectomy or hysterectomy).
Criteria for continuation of treatment in the setting of progressive disease
For all patients who are treated through progression at the Investigator’s discretion, the Investigator
should ensure that patients still meet all of the inclusion criteria and none of the exclusion criteria for
this study, and that patients meet the following specific criteria for treatment in the setting of PD:
1. Written informed consent to continue treatment or retreatment in the setting of PD. This
consent document will specify that treatment beyond initial evidence of PD is not the
“standard-of-care” and that alternative treatment options, either locally licensed treatments or
other clinical trials, are available for this patient population.
2. Absence of clinical symptoms or signs indicating clinically significant disease progression
3. No decline in WHO/ECOG performance status to >1
4. Absence of rapid disease progression or threat to vital organs or critical anatomical sites (eg,
central nervous system metastasis, respiratory failure due to tumor compression, or spinal cord
compression) requiring urgent alternative medical intervention
The IP should be discontinued if there is confirmed PD while receiving IMT following a
previous response (CR or PR) to the IP in the target lesions (ie, the response and progression
events both occurred in the target lesions while receiving the IP during the treatment period).
Criteria for retreatment in the MEDI4736 + tremelimumab arm
Patients in the MEDI4736 + tremelimumab combination therapy arm are eligible to receive
retreatment with the MEDI4736 + tremelimumab combination therapy provided progression
occurred in the monotherapy portion of dosing and the patient meets all the criteria specified above
for treatment beyond confirmed progression. Patients who discontinue treatment in 1 treatment arm
may not switch to treatment in a different group.
Exclusion Criteria
Exclusion criteria:
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Histologically confirmed head and neck cancer of any other primary anatomic location in the
head and neck not specified in the inclusion criteria including patients with SCCHN of
unknown primary or non-squamous histologies (eg, nasopharynx or salivary gland)
2. Received any systemic therapy for recurrent or metastatic SCCHN
3. Tumor progression or recurrence within 6 months of last dose of platinum therapy in the
primary treatment setting
4. Receipt of any radiotherapy or hormonal therapy for cancer treatment within 30 days prior to
first dose of study treatment
5. Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted
therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose of study treatment. If
sufficient washout time has not occurred due to the schedule or PK properties of an agent, a
longer washout period will be required, as agreed upon by AstraZeneca and the Investigator.
6. Receipt of any investigational anticancer therapy within 28 days or 5 half-lives, whichever is
shorter, prior to the first dose of study treatment.
7. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose
of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
8. Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for
Adverse Event (CTCAE) Grade ≥2 from previous anticancer therapy with the exception of
alopecia, vitiligo, lymphopenia, and the laboratory values defined in the inclusion criterion
- Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis and may be
included after consultation with the Study Physician.
- Patients with a toxicity not reasonably expected to be exacerbated by treatment with their
assigned IP (eg, hearing loss) may be included after consultation with the Study Physician.
9. Current or prior use of immunosuppressive medication within 14 days before the first dose of
their assigned IP. The following are exceptions to this criterion unless otherwise indicated:
- 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 pre-medication for hypersensitivity reactions (eg, CT scan pre-medication)
10. History of allogeneic organ transplantation
11. Active or prior documented autoimmune or inflammatory disorders (including inflammatory
bowel disease [eg, colitis, Crohn’s disease], diverticulitis with the exception of a prior episode
that has resolved or diverticulosis, celiac disease, or other serious gastrointestinal chronic
conditions associated with diarrhea; systemic lupus erythematosus; Wegener syndrome
[granulomatosis with polyangiitis]; myasthenia gravis; 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
12. Uncontrolled intercurrent illness, including, but not limited to ongoing or active infection,
symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris,
cardiac arrhythmia, interstitial lung disease, or psychiatric illness or social situations that would
limit compliance with study requirements, substantially increase the risk of incurring AEs from
IP, or compromise the ability of the patient to give written informed consent
13. History of another primary malignancy within the last 5 years except for the following:
- Non-invasive malignancies, such as cervical carcinoma in situ or nonmelanomatous
carcinoma of the skin that has been surgically cured. Other in situ carcinomas that have been
adequately treated may be permitted after detailed discussion with the Sponsor.
14. Patients with a history of brain metastases, spinal cord compression, or leptomeningeal
carcinomatosis, or involvement of any other anatomic area that, in the opinion of the
Investigator, may cause significant symptoms if an inflammatory reaction occurs
15. Mean QT interval corrected for heart rate ≥470 ms calculated from 3 electrocardiograms
(ECGs) using Fridericia’s Correction
16. History of active primary immunodeficiency
17. Known history of previous clinical diagnosis of tuberculosis
18. Active infection including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
19. Receipt of live, attenuated vaccine within 30 days prior to the first dose of IP.
Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days
after the last dose of IP.
20. Female patients who are pregnant or breast-feeding or male or female patients of reproductive
potential who are not willing to employ effective birth control from screening to 90 days after
the last dose of MEDI4736 monotherapy or 180 days after the last dose of MEDI4736 +
tremelimumab combination therapy. For patients randomized to receive SoC treatment, follow
the local prescribing information relating to contraception, the time limit for such precautions,
and any additional restrictions for agents in the SoC treatment regimen.
21. Known allergy or hypersensitivity to IP or any IP excipient
22. Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP
or interpretation of patient safety or stud results
23. For patients randomized to the SoC arm, any contraindication to a specific SoC agent as
specified by the accompanying package insert or Summary of Product Characteristics
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Histologically confirmed head and neck cancer of any other primary anatomic location in the
head and neck not specified in the inclusion criteria including patients with SCCHN of
unknown primary or non-squamous histologies (eg, nasopharynx or salivary gland)
2. Received any systemic therapy for recurrent or metastatic SCCHN
3. Tumor progression or recurrence within 6 months of last dose of platinum therapy in the
primary treatment setting
4. Receipt of any radiotherapy or hormonal therapy for cancer treatment within 30 days prior to
first dose of study treatment
5. Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted
therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose of study treatment. If
sufficient washout time has not occurred due to the schedule or PK properties of an agent, a
longer washout period will be required, as agreed upon by AstraZeneca and the Investigator.
6. Receipt of any investigational anticancer therapy within 28 days or 5 half-lives, whichever is
shorter, prior to the first dose of study treatment.
7. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose
of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
8. Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for
Adverse Event (CTCAE) Grade ≥2 from previous anticancer therapy with the exception of
alopecia, vitiligo, lymphopenia, and the laboratory values defined in the inclusion criterion
- Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis and may be
included after consultation with the Study Physician.
- Patients with a toxicity not reasonably expected to be exacerbated by treatment with their
assigned IP (eg, hearing loss) may be included after consultation with the Study Physician.
9. Current or prior use of immunosuppressive medication within 14 days before the first dose of
their assigned IP. The following are exceptions to this criterion unless otherwise indicated:
- 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 pre-medication for hypersensitivity reactions (eg, CT scan pre-medication)
10. History of allogeneic organ transplantation
11. Active or prior documented autoimmune or inflammatory disorders (including inflammatory
bowel disease [eg, colitis, Crohn’s disease], diverticulitis with the exception of a prior episode
that has resolved or diverticulosis, celiac disease, or other serious gastrointestinal chronic
conditions associated with diarrhea; systemic lupus erythematosus; Wegener syndrome
[granulomatosis with polyangiitis]; myasthenia gravis; 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
12. Uncontrolled intercurrent illness, including, but not limited to ongoing or active infection,
symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris,
cardiac arrhythmia, interstitial lung disease, or psychiatric illness or social situations that would
limit compliance with study requirements, substantially increase the risk of incurring AEs from
IP, or compromise the ability of the patient to give written informed consent
13. History of another primary malignancy within the last 5 years except for the following:
- Non-invasive malignancies, such as cervical carcinoma in situ or nonmelanomatous
carcinoma of the skin that has been surgically cured. Other in situ carcinomas that have been
adequately treated may be permitted after detailed discussion with the Sponsor.
14. Patients with a history of brain metastases, spinal cord compression, or leptomeningeal
carcinomatosis, or involvement of any other anatomic area that, in the opinion of the
Investigator, may cause significant symptoms if an inflammatory reaction occurs
15. Mean QT interval corrected for heart rate ≥470 ms calculated from 3 electrocardiograms
(ECGs) using Fridericia’s Correction
16. History of active primary immunodeficiency
17. Known history of previous clinical diagnosis of tuberculosis
18. Active infection including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
19. Receipt of live, attenuated vaccine within 30 days prior to the first dose of IP.
Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days
after the last dose of IP.
20. Female patients who are pregnant or breast-feeding or male or female patients of reproductive
potential who are not willing to employ effective birth control from screening to 90 days after
the last dose of MEDI4736 monotherapy or 180 days after the last dose of MEDI4736 +
tremelimumab combination therapy. For patients randomized to receive SoC treatment, follow
the local prescribing information relating to contraception, the time limit for such precautions,
and any additional restrictions for agents in the SoC treatment regimen.
21. Known allergy or hypersensitivity to IP or any IP excipient
22. Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP
or interpretation of patient safety or stud results
23. For patients randomized to the SoC arm, any contraindication to a specific SoC agent as
specified by the accompanying package insert or Summary of Product Characteristics
The Estimated Number of Participants
-
Taiwan
40 participants
-
Global
630 participants
