Clinical Trials List
Protocol NumberGO28915
NCT Number(ClinicalTrials.gov Identfier)NCT02008227
2014-01-01 - 2019-06-20
Phase III
Terminated4
ICD-10C34.80
Malignant neoplasm of overlapping sites of unspecified bronchus and lung
ICD-10C34.81
Malignant neoplasm of overlapping sites of right bronchus and lung
ICD-10C34.82
Malignant neoplasm of overlapping sites of left bronchus and lung
ICD-10C7A.090
Malignant carcinoid tumor of the bronchus and lung
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.8
Malignant neoplasm of other parts of bronchus or lung
A PHASE III, OPEN-LABEL, MULTICENTER, RANDOMIZED STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF MPDL3280A (ANTIPD-L1 ANTIBODY) COMPARED WITH DOCETAXEL IN PATIENTS WITH NON-SMALL CELL LUNG CANCER AFTER FAILURE WITH PLATINUM-CONTAINING
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Trial Applicant
-
Sponsor
F. Hoffmann-La Roche AG
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Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Jen-Fu Shih 未分科
- 吳杰鴻 無
- Chao-Hua Chiu 無
- 施政甫 未分科
- 施政甫醫師 無
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chun-Hua Wang 無
- Fu-Tsai Chung 無
- Chih-Teng Yu 無
- 枋岳甫 無
- Pai-Chien Chou 無
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 廖偉志 無
- 陳鴻仁 無
- Chih-Yen Tu 無
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Jih-Hsiang Lee 無
- 陳冠宇 無
- James Chih-Hsin Yang 無
- CHAO-CHI HO CHAO-CHI HO 無
- 廖唯昱 無
- JIN-YUAN SHIH 無
- 蔡子修 無
- Chia-Chi Lin 無
- 林宗哲 無
- 林育麟 無
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Non-Small Cell Lung Cancer
Objectives
The primary efficacy objective for this study is:
To determine if MPDL3280A treatment results in an improved overall survival (OS)
compared with docetaxel treatment in patients with locally advanced or metastatic
non-small cell lung cancer (NSCLC) who have progressed during or following a
platinum-containing regimen Comparisons of OS between the treatment arms within each subgroup of the immunohistochemistry (IHC) strata and within the overall intent-to-treat (ITT) population will be tested using a hierarchical fixed-sequence procedure (IHC 2/3 IHC 1/2/3 IHC 0/1/2/3).
Test Drug
TECENTRIQ® (Atezolizumab)
Active Ingredient
MPDL3280A
Dosage Form
Injection
Dosage
60mg/mL (1200mg/20mL/Vial)
Endpoints
Efficacy Objectives
The primary efficacy objective for this study is:
To determine if MPDL3280A treatment results in an improved overall survival (OS)
compared with docetaxel treatment in patients with locally advanced or metastatic
non-small cell lung cancer (NSCLC) who have progressed during or following a
platinum-containing regimen
Comparisons of OS between the treatment arms within each subgroup of the
immunohistochemistry (IHC) strata and within the overall intent-to-treat (ITT) population will be
tested using a hierarchical fixed-sequence procedure (IHC 2/3 IHC 1/2/3 IHC 0/1/2/3).
The secondary efficacy objectives for this study are:
To evaluate the efficacy of MPDL3280A compared with docetaxel with respect to antitumor
effects as measured by objective response rate (ORR) per investigator using Response
Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
To evaluate the efficacy of MPDL3280A compared with docetaxel with respect to antitumor effects as measured by progression-free survival (PFS) per investigator using RECIST v1.1
To evaluate the efficacy of MPDL3280A compared with docetaxel with respect to antitumor effects as measured by duration of response (DOR) per RECIST v1.1
The primary efficacy objective for this study is:
To determine if MPDL3280A treatment results in an improved overall survival (OS)
compared with docetaxel treatment in patients with locally advanced or metastatic
non-small cell lung cancer (NSCLC) who have progressed during or following a
platinum-containing regimen
Comparisons of OS between the treatment arms within each subgroup of the
immunohistochemistry (IHC) strata and within the overall intent-to-treat (ITT) population will be
tested using a hierarchical fixed-sequence procedure (IHC 2/3 IHC 1/2/3 IHC 0/1/2/3).
The secondary efficacy objectives for this study are:
To evaluate the efficacy of MPDL3280A compared with docetaxel with respect to antitumor
effects as measured by objective response rate (ORR) per investigator using Response
Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
To evaluate the efficacy of MPDL3280A compared with docetaxel with respect to antitumor effects as measured by progression-free survival (PFS) per investigator using RECIST v1.1
To evaluate the efficacy of MPDL3280A compared with docetaxel with respect to antitumor effects as measured by duration of response (DOR) per RECIST v1.1
Inclution Criteria
Signed Informed Consent Form
Ability to comply with protocol
Aged 18 years
Histologically or cytologically documented locally advanced or metastatic (i.e., Stage IIIB
not eligible for definitive chemoradiotherapy, Stage IV, or recurrent) NSCLC (per the Union
Internationale Contre le Cancer [UICC]/American Joint Committee on Cancer [AJCC]
staging system, 7th edition; Detterbeck et al. 2009); pathological characterization must be
sufficient to define patients as having either squamous or nonsquamous histology.
Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin
blocks (preferred) or at least 15 unstained slides, with an associated pathology report, for
central testing and determined to be evaluable for tumor PD-L1 expression prior to study
enrollment; patients with fewer than 15 unstained slides available at baseline (but no fewer
than 10) may be eligible following discussion with Medical Monitor.
Tumor tissue should be of good quality based on total and viable tumor content.
Fine-needle aspiration, brushing, cell pellet from pleural effusion, and lavage samples
are not acceptable. For core needle biopsy specimens, at least three cores should be
submitted for evaluation.
Patients who do not have tissue specimens meeting eligibility requirements may
undergo a biopsy during the screening period. Acceptable samples include core
needle biopsies for deep tumor tissue (minimum 3 cores) or excisional, incisional,
punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions.
Tumor tissue from bone metastases is not evaluable for tumor PD-L1 expression and is
therefore not acceptable.
Patients having additional tissue samples from procedures performed at different
times during the course of their NSCLC will be requested (but not required) to also
submit these samples for central testing. Tissue samples obtained at multiple times
for individual patients will greatly contribute to an improved understanding of the
dynamics of PD-L1 expression and relationship with intervening anticancer therapy.
Disease progression during or following treatment with a prior platinum-containing regimen
for locally advanced, unresectable/inoperable or metastatic NSCLC or disease recurrence
within 6 months of treatment with a platinum-based adjuvant/neoadjuvant regimen
Adjuvant/neoadjuvant chemotherapy or chemoradiation counts as a prior
chemotherapy regimen if 6 months have elapsed between the last dose and the date
of recurrence. Combined treatment with chemotherapy and radiation constitutes a
single regimen; surgery is not considered a regimen.
Patients may have received one additional cytotoxic chemotherapy regimen
(maximum of two prior cytotoxic chemotherapy regimens).
Chemotherapy regimens will be counted based on interval disease progression and
not the number of agents or switches in agents (e.g., a first-line therapy that consists
of several cycles of a platinum doublet and subsequent maintenance therapy that
introduces or switches to a new chemotherapy agent without interval disease
progression will all be considered one chemotherapy regimen).
Patients with advanced lung cancer and a sensitizing EGFR mutation will additionally
be required to have experienced disease progression (during or after treatment) with
an EGFR TKI (erlotinib, gefitinib, etc.). Patients with unknown EGFR mutational status
not previously treated with an EGFR TKI but whose tumor may harbor a sensitizing
EGFR mutation (i.e., nonsquamous histology, KRAS status wild-type or unknown, ALK
fusion oncogene negative or unknown) will be tested by a central laboratory prior to
enrollment
Patients with a previously detected ALK fusion oncogene must additionally have
experienced disease progression (during or after treatment) with crizotinib or another
ALK inhibitor.
The last dose of prior systemic anticancer therapy must have been
administered 21 days prior to randomization, with the exception being TKIs approved
for treatment of NSCLC have to be discontinued 7 days prior to Cycle 1, Day 1. The
baseline scan must be obtained after discontinuation of prior TKIs.
The last dose of treatment with any investigational agent or participation in another
clinical trial with therapeutic intent must have ended 28 days prior to randomization.
Anticancer agents used for pleurodesis are not counted as a line of therapy.
Prior radiation therapy is allowed provided the patient has recovered from any toxic
effects thereof and 7 days have elapsed between the last fraction and randomization.
Measurable disease, as defined by RECIST v1.1
ECOG performance status of 0 or 1
Life expectancy 12 weeks
Adequate hematologic and end organ function, defined by the following laboratory results
obtained within 14 days prior to the first study treatment:
ANC 1500 cells/L (without granulocyte colony-stimulating factor support within
2 weeks of laboratory test used to determine eligibility)
WBC counts 2500/L
Lymphocyte count 500/L
Serum albumin 2.5 g/dL
Platelet count 100,000/L (without transfusion within 2 weeks of laboratory test used
to determine eligibility)
Hemoglobin 9.0 g/dL
Patients may be transfused or receive erythropoietic treatment to meet this
criterion.
Liver function tests meeting one of the following criteria:
AST or ALT 2.5 upper limit of normal (ULN), with alkaline phosphatase
2.5 ULN
or
AST and ALT 1.5 ULN, with alkaline phosphatase 2.5 ULN
Serum bilirubin 1.0 ULN
Patients with known Gilbert’s disease who have serum bilirubin level 3 ULN
may be enrolled.
INR and aPTT 1.5 ULN
This applies only to patients who are not receiving therapeutic anticoagulation;
patients receiving therapeutic anticoagulation should be on a stable dose for at
least 1 week prior to randomization.
Creatinine clearance 30 mL/min
Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI),
or Modification of Diet in Renal Disease (MDRD) formulas may be used for
creatinine clearance calculation. Note that 24-hour urine collection is not required.
For female patients of childbearing potential and male patients with partners of childbearing
potential, agreement (by patient and/or partner) to use highly effective form(s) of
contraception (i.e., one that results in a low failure rate [ 1% per year] when used
consistently and correctly) and to continue its use for 6 months after the last dose of
MPDL3280A
Patients must have recovered from all acute toxicities from previous therapy, excluding
alopecia
Ability to comply with protocol
Aged 18 years
Histologically or cytologically documented locally advanced or metastatic (i.e., Stage IIIB
not eligible for definitive chemoradiotherapy, Stage IV, or recurrent) NSCLC (per the Union
Internationale Contre le Cancer [UICC]/American Joint Committee on Cancer [AJCC]
staging system, 7th edition; Detterbeck et al. 2009); pathological characterization must be
sufficient to define patients as having either squamous or nonsquamous histology.
Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin
blocks (preferred) or at least 15 unstained slides, with an associated pathology report, for
central testing and determined to be evaluable for tumor PD-L1 expression prior to study
enrollment; patients with fewer than 15 unstained slides available at baseline (but no fewer
than 10) may be eligible following discussion with Medical Monitor.
Tumor tissue should be of good quality based on total and viable tumor content.
Fine-needle aspiration, brushing, cell pellet from pleural effusion, and lavage samples
are not acceptable. For core needle biopsy specimens, at least three cores should be
submitted for evaluation.
Patients who do not have tissue specimens meeting eligibility requirements may
undergo a biopsy during the screening period. Acceptable samples include core
needle biopsies for deep tumor tissue (minimum 3 cores) or excisional, incisional,
punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions.
Tumor tissue from bone metastases is not evaluable for tumor PD-L1 expression and is
therefore not acceptable.
Patients having additional tissue samples from procedures performed at different
times during the course of their NSCLC will be requested (but not required) to also
submit these samples for central testing. Tissue samples obtained at multiple times
for individual patients will greatly contribute to an improved understanding of the
dynamics of PD-L1 expression and relationship with intervening anticancer therapy.
Disease progression during or following treatment with a prior platinum-containing regimen
for locally advanced, unresectable/inoperable or metastatic NSCLC or disease recurrence
within 6 months of treatment with a platinum-based adjuvant/neoadjuvant regimen
Adjuvant/neoadjuvant chemotherapy or chemoradiation counts as a prior
chemotherapy regimen if 6 months have elapsed between the last dose and the date
of recurrence. Combined treatment with chemotherapy and radiation constitutes a
single regimen; surgery is not considered a regimen.
Patients may have received one additional cytotoxic chemotherapy regimen
(maximum of two prior cytotoxic chemotherapy regimens).
Chemotherapy regimens will be counted based on interval disease progression and
not the number of agents or switches in agents (e.g., a first-line therapy that consists
of several cycles of a platinum doublet and subsequent maintenance therapy that
introduces or switches to a new chemotherapy agent without interval disease
progression will all be considered one chemotherapy regimen).
Patients with advanced lung cancer and a sensitizing EGFR mutation will additionally
be required to have experienced disease progression (during or after treatment) with
an EGFR TKI (erlotinib, gefitinib, etc.). Patients with unknown EGFR mutational status
not previously treated with an EGFR TKI but whose tumor may harbor a sensitizing
EGFR mutation (i.e., nonsquamous histology, KRAS status wild-type or unknown, ALK
fusion oncogene negative or unknown) will be tested by a central laboratory prior to
enrollment
Patients with a previously detected ALK fusion oncogene must additionally have
experienced disease progression (during or after treatment) with crizotinib or another
ALK inhibitor.
The last dose of prior systemic anticancer therapy must have been
administered 21 days prior to randomization, with the exception being TKIs approved
for treatment of NSCLC have to be discontinued 7 days prior to Cycle 1, Day 1. The
baseline scan must be obtained after discontinuation of prior TKIs.
The last dose of treatment with any investigational agent or participation in another
clinical trial with therapeutic intent must have ended 28 days prior to randomization.
Anticancer agents used for pleurodesis are not counted as a line of therapy.
Prior radiation therapy is allowed provided the patient has recovered from any toxic
effects thereof and 7 days have elapsed between the last fraction and randomization.
Measurable disease, as defined by RECIST v1.1
ECOG performance status of 0 or 1
Life expectancy 12 weeks
Adequate hematologic and end organ function, defined by the following laboratory results
obtained within 14 days prior to the first study treatment:
ANC 1500 cells/L (without granulocyte colony-stimulating factor support within
2 weeks of laboratory test used to determine eligibility)
WBC counts 2500/L
Lymphocyte count 500/L
Serum albumin 2.5 g/dL
Platelet count 100,000/L (without transfusion within 2 weeks of laboratory test used
to determine eligibility)
Hemoglobin 9.0 g/dL
Patients may be transfused or receive erythropoietic treatment to meet this
criterion.
Liver function tests meeting one of the following criteria:
AST or ALT 2.5 upper limit of normal (ULN), with alkaline phosphatase
2.5 ULN
or
AST and ALT 1.5 ULN, with alkaline phosphatase 2.5 ULN
Serum bilirubin 1.0 ULN
Patients with known Gilbert’s disease who have serum bilirubin level 3 ULN
may be enrolled.
INR and aPTT 1.5 ULN
This applies only to patients who are not receiving therapeutic anticoagulation;
patients receiving therapeutic anticoagulation should be on a stable dose for at
least 1 week prior to randomization.
Creatinine clearance 30 mL/min
Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI),
or Modification of Diet in Renal Disease (MDRD) formulas may be used for
creatinine clearance calculation. Note that 24-hour urine collection is not required.
For female patients of childbearing potential and male patients with partners of childbearing
potential, agreement (by patient and/or partner) to use highly effective form(s) of
contraception (i.e., one that results in a low failure rate [ 1% per year] when used
consistently and correctly) and to continue its use for 6 months after the last dose of
MPDL3280A
Patients must have recovered from all acute toxicities from previous therapy, excluding
alopecia
Exclusion Criteria
Active or untreated CNS metastases as determined by CT or MRI evaluation during
screening and prior radiographic assessments
Patients with a history of treated asymptomatic CNS metastases are eligible, provided
they meet all of the following criteria:
Measurable disease outside the CNS
Only supratentorial metastases allowed (i.e., no metastases to midbrain, pons,
cerebellum, medulla, or spinal cord)
No history of intracranial hemorrhage
No ongoing requirement for corticosteroids as therapy for CNS disease;
anticonvulsants at a stable dose allowed
No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior
to Cycle 1, Day 1
No evidence of interim progression between the completion of CNS-directed
therapy and the screening radiographic study
Note: Patients with new asymptomatic CNS metastases detected at the screening
scan must receive radiation therapy and/or surgery for CNS metastases.
Following treatment, these patients may then be eligible without the need for an
additional brain scan prior to enrollment, if all other criteria are met.
Spinal cord compression not definitively treated with surgery and/or radiation or previously
diagnosed and treated spinal cord compression without evidence that disease has been
clinically stable for 2 weeks prior to randomization
Leptomeningeal disease
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage
procedures
Uncontrolled tumor-related pain
Patients requiring pain medication must be on a stable regimen at study entry.
Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases
or metastases causing nerve impingement) should be treated prior to enrollment.
Asymptomatic metastatic lesions whose further growth would likely cause
functional deficits or intractable pain (e.g., epidural metastasis that is not presently
associated with spinal cord compression) should be considered for loco-regional
therapy if appropriate prior to enrollment.
Uncontrolled hypercalcemia ( 1.5 mmol/L ionized calcium or Ca 12 mg/dL or corrected
serum calcium ULN) or symptomatic hypercalcemia requiring continued use of
bisphosphonate therapy or denosumab
Patients who are receiving bisphosphonate therapy or denosumab specifically to
prevent skeletal events and who do not have a history of clinically significant
hypercalcemia are eligible.
Patients who are receiving denosumab prior to enrollment must be willing and eligible
to discontinue its use and replace it with a bisphosphonate instead while on study.
Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative
outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous
cell skin cancer, localized prostate cancer treated with curative intent, or ductal carcinoma
in situ treated surgically with curative intent)
screening and prior radiographic assessments
Patients with a history of treated asymptomatic CNS metastases are eligible, provided
they meet all of the following criteria:
Measurable disease outside the CNS
Only supratentorial metastases allowed (i.e., no metastases to midbrain, pons,
cerebellum, medulla, or spinal cord)
No history of intracranial hemorrhage
No ongoing requirement for corticosteroids as therapy for CNS disease;
anticonvulsants at a stable dose allowed
No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior
to Cycle 1, Day 1
No evidence of interim progression between the completion of CNS-directed
therapy and the screening radiographic study
Note: Patients with new asymptomatic CNS metastases detected at the screening
scan must receive radiation therapy and/or surgery for CNS metastases.
Following treatment, these patients may then be eligible without the need for an
additional brain scan prior to enrollment, if all other criteria are met.
Spinal cord compression not definitively treated with surgery and/or radiation or previously
diagnosed and treated spinal cord compression without evidence that disease has been
clinically stable for 2 weeks prior to randomization
Leptomeningeal disease
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage
procedures
Uncontrolled tumor-related pain
Patients requiring pain medication must be on a stable regimen at study entry.
Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases
or metastases causing nerve impingement) should be treated prior to enrollment.
Asymptomatic metastatic lesions whose further growth would likely cause
functional deficits or intractable pain (e.g., epidural metastasis that is not presently
associated with spinal cord compression) should be considered for loco-regional
therapy if appropriate prior to enrollment.
Uncontrolled hypercalcemia ( 1.5 mmol/L ionized calcium or Ca 12 mg/dL or corrected
serum calcium ULN) or symptomatic hypercalcemia requiring continued use of
bisphosphonate therapy or denosumab
Patients who are receiving bisphosphonate therapy or denosumab specifically to
prevent skeletal events and who do not have a history of clinically significant
hypercalcemia are eligible.
Patients who are receiving denosumab prior to enrollment must be willing and eligible
to discontinue its use and replace it with a bisphosphonate instead while on study.
Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative
outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous
cell skin cancer, localized prostate cancer treated with curative intent, or ductal carcinoma
in situ treated surgically with curative intent)
The Estimated Number of Participants
-
Taiwan
16 participants
-
Global
1300 participants
