Clinical Trials List
Protocol NumberD4191C00003
2014-05-01 - 2023-09-30
Phase II
Terminated5
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
ICD-10C34.91
Malignant neoplasm of unspecified part of right bronchus or lung
ICD-10C34.92
Malignant neoplasm of unspecified part of left bronchus or lung
ICD-10C7A.090
Malignant carcinoid tumor of the bronchus and lung
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Phase II, Non-comparative, Open label, Multi-centre, International Study of MEDI4736, in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV) who have received at least Two Prior Systemic Treatment Regimens Including One Platinum-based Chemotherapy Regimen (ATLANTIC)
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
AstraZeneca AB
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Jen-Fu Shih Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Jih-Hsiang Lee Division of Hematology & Oncology
- 陳冠宇 Division of General Internal Medicine
- 林育麟 Division of Hematology & Oncology
- 廖唯昱 Division of General Internal Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- JIN-YUAN SHIH Division of General Internal Medicine
- 蔡子修 Division of General Internal Medicine
- Chong-Jen Yu Division of General Internal Medicine
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- JENG-SEN TSENG Division of Thoracic Medicine
- TSUNG -YING YANG Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
- 陳焜結 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Shang-Yin Wu Division of Hematology & Oncology
- Wu-Chou Su Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 陳鴻仁 Division of Thoracic Medicine
- Chen Chia-Hung Division of Thoracic Medicine
- Chih-Yen Tu Division of Thoracic Medicine
- Wei-Chun Chen Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Non-Small Cell Lung Cancer
Objectives
Primary Objective:
To assess the efficacy of MEDI4736 treatment in terms of ORR
Secondary Objective:
To further assess the efficacy of MEDI4736 in terms of: DoR, PFS, DCR, OS, and DSR
To assess the safety and tolerability profile of MEDI4736
To assess the PK of MEDI4736
To investigate the immunogenicity of MEDI4736
Exploratory Objective:
To explore immune-related response criteria as an assessment methodology for clinical benefit of MEDI4736 by Independent Central Review.
To investigate the relationship between MEDI4736 PK exposure and clinical outcomes, efficacy, AEs and/or safety parameters, if deemed appropriate.
To collect blood and tissue samples for analysis of biomarkers including but not limited to: immune cell gene expression profiles within the peripheral and tumoural compartments, the presence of IFN-γ tumour necrosis factor-α, IL-2, IL-6, IL-10, IL-8, and IL-12 as well as antibodies against tumour, self, or viral antigens, expression of PD-L1 and the number and
phenotype of immune cells such as T-cells.
To explore the relationship(s) between a patient’s biomarker status before and after treatment with MEDI4736 and MEDI4736 PK exposure, clinical outcomes, efficacy, AEs and/or safety parameters.
To explore potential biomarkers in residual biological samples (eg, tumour, plasma and/or serum), which may influence the progression of cancer (and associated clinical characteristics) and/or prospectively identify patients likely to respond to MEDI4736 treatment.
To collect and store DNA according to each country’s local and ethical procedures for future exploratory research into genes/genetic variation that may influence response (ie, distribution, safety, tolerability and efficacy) to study treatments and/or susceptibility
to disease (optional).
Test Drug
MEDI4736
Active Ingredient
MEDI4736
Dosage Form
lyophilised powder for infusion
Dosage
200 mg/vial
Endpoints
To assess the efficacy of MEDI4736 treatment in terms of ORR
To further assess the efficacy of MEDI4736 in terms of: DoR, PFS, DCR, OS, and DSR
To assess the safety and tolerability profile of MEDI4736
To assess the PK of MEDI4736
To investigate the immunogenicity of MEDI4736
To further assess the efficacy of MEDI4736 in terms of: DoR, PFS, DCR, OS, and DSR
To assess the safety and tolerability profile of MEDI4736
To assess the PK of MEDI4736
To investigate the immunogenicity of MEDI4736
Inclution Criteria
1. Provision of signed, written and dated informed consent prior to any study specific
procedures
2. Male or female aged 18 years or older
3. Patients must have EITHER
• Histologically- or cytologically-documented NSCLC who present with Stage IIIB/
Stage IV disease (according to Version 7 of the International Association for the
Study of Lung Cancer Staging Manual in Thoracic Oncology [IASLC Staging
Manual in Thoracic Oncology]), OR
• Recurrent or progressive disease following multimodal therapy (radiation therapy,
surgical resection, or definitive chemoradiation therapy for locally advanced
disease)
4. Patients must have received at least 2 prior systemic treatment regimens for
treatment of NSCLC
5. Patients must have experienced disease progression or recurrence after both a
platinum-based chemotherapy regimen and at least 1 additional systemic therapy
• Patients with tumours with activating EGFR TK mutations must have received an
EGFR TKI and patients with tumours that are ALK fusion positive must have
received an ALK TKI, given before or after the platinum-based chemotherapy
regimen
• Maintenance therapy following platinum doublet-based chemotherapy is not
considered a separate regimen of therapy
• Prior platinum-containing adjuvant, neoadjuvant or definitive chemoradiation
therapy given for locally advanced disease is considered first-line therapy only if
recurrent (local or metastatic) disease developed within 6 months of completing
therapy. Patients with recurrent disease >6 months must also have progressed after
a subsequent platinum-based chemotherapy regimen given to treat the recurrence.
6. Patient’s tumour sample must be PD-L1 positive (either recent or archival sample)
based on central assessment, subject to availability of the PD-L1 diagnostic.
Sample requirements as follows:
• A mandatory provision of a recent (≤3 months) tumour biopsy taken following the
completion of the most recent systemic anti-cancer therapy, except if technically
not feasible and after discussion with the study physician (for collection and processing procedures, refer to Section 6.6.1 and the Laboratory Manual). Tumour
lesions planned for biopsy must not be used as index lesions for assessment of
disease
AND
• Provision of an archived tumour tissue block (or at least 10 newly cut unstained
slides) where such samples exist in a quantity sufficient to allow for analysis (refer
to Section 6.6.1 and the Laboratory Manual for details).
7. Patients must have measurable disease, at least 1 lesion, not previously irradiated,
which can be accurately measured at baseline as ≥10 mm in the longest diameter
(except lymph nodes that must have short axis ≥15 mm) with CT or MRI and which
is suitable for accurate repeated measurements per RECIST v1.1 guidelines
8. Life expectancy ≥12 weeks at Day 1
9. World Health Organisation (WHO) Performance Status of 0 or 1
10. 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 are amenorrheic for 12 months without an alternative medical cause. The
following age-specific requirements apply:
• Women <50 years old would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and with luteinizing hormone and follicle-stimulating 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, radiation-induced oophorectomy with last menses >1 year ago,
chemotherapy-induced menopause with >1 year interval since last menses, or
surgical sterilisation (bilateral oophorectomy or hysterectomy).
11. Adequate organ and marrow function as defined below:
• Absolute neutrophil count >1.5 x 109/L (1500 per mm3)
• Platelets >100 x 109/L (100,000 per mm3)
• Haemoglobin ≥9.0 g/dL (5.59 mmol/L).
procedures
2. Male or female aged 18 years or older
3. Patients must have EITHER
• Histologically- or cytologically-documented NSCLC who present with Stage IIIB/
Stage IV disease (according to Version 7 of the International Association for the
Study of Lung Cancer Staging Manual in Thoracic Oncology [IASLC Staging
Manual in Thoracic Oncology]), OR
• Recurrent or progressive disease following multimodal therapy (radiation therapy,
surgical resection, or definitive chemoradiation therapy for locally advanced
disease)
4. Patients must have received at least 2 prior systemic treatment regimens for
treatment of NSCLC
5. Patients must have experienced disease progression or recurrence after both a
platinum-based chemotherapy regimen and at least 1 additional systemic therapy
• Patients with tumours with activating EGFR TK mutations must have received an
EGFR TKI and patients with tumours that are ALK fusion positive must have
received an ALK TKI, given before or after the platinum-based chemotherapy
regimen
• Maintenance therapy following platinum doublet-based chemotherapy is not
considered a separate regimen of therapy
• Prior platinum-containing adjuvant, neoadjuvant or definitive chemoradiation
therapy given for locally advanced disease is considered first-line therapy only if
recurrent (local or metastatic) disease developed within 6 months of completing
therapy. Patients with recurrent disease >6 months must also have progressed after
a subsequent platinum-based chemotherapy regimen given to treat the recurrence.
6. Patient’s tumour sample must be PD-L1 positive (either recent or archival sample)
based on central assessment, subject to availability of the PD-L1 diagnostic.
Sample requirements as follows:
• A mandatory provision of a recent (≤3 months) tumour biopsy taken following the
completion of the most recent systemic anti-cancer therapy, except if technically
not feasible and after discussion with the study physician (for collection and processing procedures, refer to Section 6.6.1 and the Laboratory Manual). Tumour
lesions planned for biopsy must not be used as index lesions for assessment of
disease
AND
• Provision of an archived tumour tissue block (or at least 10 newly cut unstained
slides) where such samples exist in a quantity sufficient to allow for analysis (refer
to Section 6.6.1 and the Laboratory Manual for details).
7. Patients must have measurable disease, at least 1 lesion, not previously irradiated,
which can be accurately measured at baseline as ≥10 mm in the longest diameter
(except lymph nodes that must have short axis ≥15 mm) with CT or MRI and which
is suitable for accurate repeated measurements per RECIST v1.1 guidelines
8. Life expectancy ≥12 weeks at Day 1
9. World Health Organisation (WHO) Performance Status of 0 or 1
10. 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 are amenorrheic for 12 months without an alternative medical cause. The
following age-specific requirements apply:
• Women <50 years old would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and with luteinizing hormone and follicle-stimulating 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, radiation-induced oophorectomy with last menses >1 year ago,
chemotherapy-induced menopause with >1 year interval since last menses, or
surgical sterilisation (bilateral oophorectomy or hysterectomy).
11. Adequate organ and marrow function as defined below:
• Absolute neutrophil count >1.5 x 109/L (1500 per mm3)
• Platelets >100 x 109/L (100,000 per mm3)
• Haemoglobin ≥9.0 g/dL (5.59 mmol/L).
Exclusion Criteria
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca/MedImmune staff and/or staff at the study site)
2. Previous drug assignment in the present study
3. Participation in another clinical study with an investigational product during the last
4 weeks.
4. Concurrent enrolment in another clinical study, unless it is an observational
(non-interventional) clinical study or the follow-up period of an interventional study
5. Mixed small cell and NSCLC histology
6. Receipt of any investigational drug within 4 weeks prior to the first dose of
MEDI4736
7. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,
endocrine therapy, targeted therapy, biologic therapy, tumour embolisation,
monoclonal antibodies) ≤21 days prior to the first dose of MEDI4736 (≤14 days
prior to the first dose of MEDI4736 for patients who have received prior TKIs [eg,
erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin
C). If sufficient wash-out time has not occurred due to the schedule or PK
properties of an agent, a longer wash-out period will be required, as agreed by
AstraZeneca/MedImmune and the investigator.
8. 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 physiological doses, which are not to
exceed 10 mg/day of prednisone, or an equivalent corticosteroid
9. Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
10. Any unresolved toxicity CTCAE >Grade 2 from previous anti-cancer therapy.
Patients with irreversible toxicity that is not reasonably expected to be exacerbated
by the investigational product may be included (eg, hearing loss) after consultation
with the AstraZeneca/MedImmune study physician.
11. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any
previous immunotherapy agent, or any unresolved irAE >Grade 1
12. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for
cancer treatment. NOTE: Local treatment of isolated lesions, excluding target
lesions, for palliative intent is acceptable (eg, by local surgery or radiotherapy).
13. Receipt of radiation therapy within 4 weeks prior to starting MEDI4736. Limited
field of radiation for palliation within 2 weeks of the first dose of study treatment is
allowed, provided:
• The lung is not in the radiation field
• Irradiated lesion(s) cannot be used as target lesions
14. Recent major surgery within 4 weeks prior to entry into the study (excluding the
placement of vascular access) that would prevent administration of investigational
product
15. Active or prior documented autoimmune disease within the past 2 years.
NOTE: Patients with vitiligo, Grave’s disease, or psoriasis not requiring systemic
treatment (within the past 2 years) are not excluded.
16. Active or prior documented inflammatory bowel disease (eg, Crohn’s disease,
ulcerative colitis)
17. History of primary immunodeficiency
18. History of organ transplant that requires therapeutic immunosuppression
19. History of hypersensitivity to MEDI4736 or any excipient
20. Brain metastases or spinal cord compression unless asymptomatic, treated and
stable off steroids and anti-convulsants for at least 1 month prior to entry into the study.
21. History of leptomeningeal carcinomatosis
22. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Bazett’s Correction
23. 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 or chronic
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
24. Known history of previous clinical diagnosis of tuberculosis
25. Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving MEDI4736
26. History of another primary malignancy within 5 years prior to starting
investigational product, except for adequately treated basal or squamous cell
carcinoma of the skin or cancer of the cervix in situ and the disease under study.
27. Female patients who are pregnant, breast-feeding or male or female patients of
reproductive potential who are not employing an effective method of birth control.
28. Any condition that, in the opinion of the investigator, would interfere with
evaluation of the investigational product or interpretation of patient safety or study
results.
29. Absence of a tumour sample (archival and recent).
2. Previous drug assignment in the present study
3. Participation in another clinical study with an investigational product during the last
4 weeks.
4. Concurrent enrolment in another clinical study, unless it is an observational
(non-interventional) clinical study or the follow-up period of an interventional study
5. Mixed small cell and NSCLC histology
6. Receipt of any investigational drug within 4 weeks prior to the first dose of
MEDI4736
7. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,
endocrine therapy, targeted therapy, biologic therapy, tumour embolisation,
monoclonal antibodies) ≤21 days prior to the first dose of MEDI4736 (≤14 days
prior to the first dose of MEDI4736 for patients who have received prior TKIs [eg,
erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin
C). If sufficient wash-out time has not occurred due to the schedule or PK
properties of an agent, a longer wash-out period will be required, as agreed by
AstraZeneca/MedImmune and the investigator.
8. 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 physiological doses, which are not to
exceed 10 mg/day of prednisone, or an equivalent corticosteroid
9. Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
10. Any unresolved toxicity CTCAE >Grade 2 from previous anti-cancer therapy.
Patients with irreversible toxicity that is not reasonably expected to be exacerbated
by the investigational product may be included (eg, hearing loss) after consultation
with the AstraZeneca/MedImmune study physician.
11. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any
previous immunotherapy agent, or any unresolved irAE >Grade 1
12. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for
cancer treatment. NOTE: Local treatment of isolated lesions, excluding target
lesions, for palliative intent is acceptable (eg, by local surgery or radiotherapy).
13. Receipt of radiation therapy within 4 weeks prior to starting MEDI4736. Limited
field of radiation for palliation within 2 weeks of the first dose of study treatment is
allowed, provided:
• The lung is not in the radiation field
• Irradiated lesion(s) cannot be used as target lesions
14. Recent major surgery within 4 weeks prior to entry into the study (excluding the
placement of vascular access) that would prevent administration of investigational
product
15. Active or prior documented autoimmune disease within the past 2 years.
NOTE: Patients with vitiligo, Grave’s disease, or psoriasis not requiring systemic
treatment (within the past 2 years) are not excluded.
16. Active or prior documented inflammatory bowel disease (eg, Crohn’s disease,
ulcerative colitis)
17. History of primary immunodeficiency
18. History of organ transplant that requires therapeutic immunosuppression
19. History of hypersensitivity to MEDI4736 or any excipient
20. Brain metastases or spinal cord compression unless asymptomatic, treated and
stable off steroids and anti-convulsants for at least 1 month prior to entry into the study.
21. History of leptomeningeal carcinomatosis
22. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Bazett’s Correction
23. 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 or chronic
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
24. Known history of previous clinical diagnosis of tuberculosis
25. Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving MEDI4736
26. History of another primary malignancy within 5 years prior to starting
investigational product, except for adequately treated basal or squamous cell
carcinoma of the skin or cancer of the cervix in situ and the disease under study.
27. Female patients who are pregnant, breast-feeding or male or female patients of
reproductive potential who are not employing an effective method of birth control.
28. Any condition that, in the opinion of the investigator, would interfere with
evaluation of the investigational product or interpretation of patient safety or study
results.
29. Absence of a tumour sample (archival and recent).
The Estimated Number of Participants
-
Taiwan
20 participants
-
Global
210 participants
