Clinical Trials List
Protocol NumberEMR100070-004
NCT Number(ClinicalTrials.gov Identfier)2014-005060-15 (EudraCT Number)
2015-06-01 - 2018-12-31
Phase III
Terminated6
ICD-10C34
Malignant neoplasm of bronchus and lung
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Phase III open-label, multicenter trial of avelumab (MSB0010718C) versus docetaxel in subjects with non-small cell lung cancer that has progressed after a platinum-containing doublet
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Merck KGaA
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- 蔡俊明 無
- Yung-Hung Luo 無
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
5 Stop recruiting
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
NSCLC
Objectives
Primary objective
To demonstrate superiority with regard to overall survival
(OS) of avelumab versus docetaxel in subjects with
programmed death ligand 1 (PD-L1) positive (+; as
determined by a companion diagnostic test under
development), non-small cell lung cancer (NSCLC) after
failure of a platinum-based doublet
Secondary objectives
Secondary objectives are as follows:
To demonstrate superiority with regard to OS of
avelumab versus docetaxel in the intention-to-treat
(ITT) population
To demonstrate superiority with regard to the objective
response rate (ORR) of avelumab versus docetaxel in
PD-L1+ subjects
To demonstrate superiority with regard to progression
free survival (PFS) of avelumab versus docetaxel in
PD-L1+ subjects
To demonstrate superiority with regard to the ORR of
avelumab versus docetaxel in the ITT population
To demonstrate superiority with regard to PFS of
avelumab versus docetaxel in the ITT population
To compare the subject-reported outcomes / quality of
life when treated with avelumab versus docetaxel
using the EuroQOL 5-dimensions questionnaire
(EQ-5D) and the European Organization for Research
and Treatment of Cancer (EORTC) QLQ-C30 and
module QLQ-LC13 in the ITT population
To determine the safety and tolerability of avelumab
Test Drug
avelumab
Active Ingredient
IgG1 isotype
Dosage Form
Injection
Dosage
20
Endpoints
The primary endpoint for the trial is OS time, defined as
the time (in months) from randomization to the date of
death.
Secondary endpoints include
PFS time according to RECIST 1.1 and as adjudicated
by the IERC,
BOR according to RECIST 1.1 and as adjudicated by
the IERC,
changes in subject-reported outcomes / quality of life
as assessed by the EQ-5D and the EORTC QLQ-C30
and module QLQ-LC13 questionnaire, and
the safety profile of the trial drugs as measured by the
incidence of AEs, serious AEs (SAEs), clinical
laboratory assessments, vital signs, physical
examination, ECG parameters, and ECOG PS.
the time (in months) from randomization to the date of
death.
Secondary endpoints include
PFS time according to RECIST 1.1 and as adjudicated
by the IERC,
BOR according to RECIST 1.1 and as adjudicated by
the IERC,
changes in subject-reported outcomes / quality of life
as assessed by the EQ-5D and the EORTC QLQ-C30
and module QLQ-LC13 questionnaire, and
the safety profile of the trial drugs as measured by the
incidence of AEs, serious AEs (SAEs), clinical
laboratory assessments, vital signs, physical
examination, ECG parameters, and ECOG PS.
Inclution Criteria
Inclusion criteria
1. Signed written informed consent before any
trial-related procedure is undertaken that is not part of
the standard patient management
2. Male or female subjects aged ≥ 18 years
3. Availability of a formalin-fixed, paraffin-embedded
block containing tumor tissue or 7 unstained tumor
slides suitable for PD-L1 expression assessment
4. Tumor determined to be evaluable for PD-L1
expression per the evaluation of a central laboratory
5. Subjects with histologically confirmed Stage IIIb/IV
or recurrent NSCLC who have experienced disease
progression
6. Subjects must have progressed after an acceptable
therapy defined as follows:
a. Subjects must have progressed during or after a
minimum of 2 cycles of 1 course of a
platinum-based combination therapy
administered for the treatment of a metastatic
disease. A history of continuation (use of a
non-platinum agent from initial combination) or
switch (use of a different agent) maintenance
therapy is permitted provided there was no
progression after the initial combination. A
switch of agents during treatment for the
management of toxicities is also permitted
provided there was no progression after the initial
combination
OR
b. Subjects must have progressed within 6 months
of completion of a platinum-based adjuvant,
neoadjuvant, or definitive chemotherapy, or
concomitant chemoradiation regimen for locally
advanced disease
7. Subjects with non-squamous cell NSCLC of unknown
EGFR mutation status will require testing (local
laboratory, or central laboratory if local testing is not
available). For subjects with a tumor that harbors an
activating EGFR mutation, acceptable prior therapy is
also defined as a treatment with an EGFR-targeting
tyrosine kinase inhibitor (TKI) given before or after
treatment with a platinum-based combination
chemotherapy as defined above. Subjects with a
tumor that harbors an activating EGFR mutation must
have failed both the platinum-based doublet and the
EGFR-targeting TKI. Treatment with more than
1 EGFR-targeting TKI is acceptable
8. ECOG PS of 0 to 1 at trial entry
9. Estimated life expectancy of more than 12 weeks
10. Adequate hematological function defined by WBC
count ≥ 2.5 × 109
/L with absolute neutrophil count
(ANC) ≥ 1.5 × 109
/L, lymphocyte count ≥ 0.5 ×
109
/L, platelet count ≥ 100 × 109
/L, and hemoglobin
≥ 9 g/dL (may have been transfused)
11. Adequate hepatic function defined by a total bilirubin
level ≤ 1.0 × the upper limit of normal (ULN) range
and aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) levels ≤ 2.5 × ULN for all
subjects
12. Adequate renal function defined by an estimated
creatinine clearance > 30 mL/min according to the
Cockcroft-Gault formula (or local institutional
standard method)
13. Effective contraception for both male and female
subjects if the risk of conception exists (Note: The
effects of the trial drug on the developing human fetus
are unknown; thus, women of childbearing potential
and men must agree to use effective contraception,
defined as 2 barrier methods, or 1 barrier method with
a spermicide, an intrauterine device, or use of oral
female contraceptive. Effective contraception must
be used 30 days prior to first trial drug administration,
for the duration of trial participation, and at least for
60 days after stopping trial participation. Should a
woman become pregnant or suspect she is pregnant
while she or her partner is participating in this trial,
the treating physician should be informed
immediately.)
1. Signed written informed consent before any
trial-related procedure is undertaken that is not part of
the standard patient management
2. Male or female subjects aged ≥ 18 years
3. Availability of a formalin-fixed, paraffin-embedded
block containing tumor tissue or 7 unstained tumor
slides suitable for PD-L1 expression assessment
4. Tumor determined to be evaluable for PD-L1
expression per the evaluation of a central laboratory
5. Subjects with histologically confirmed Stage IIIb/IV
or recurrent NSCLC who have experienced disease
progression
6. Subjects must have progressed after an acceptable
therapy defined as follows:
a. Subjects must have progressed during or after a
minimum of 2 cycles of 1 course of a
platinum-based combination therapy
administered for the treatment of a metastatic
disease. A history of continuation (use of a
non-platinum agent from initial combination) or
switch (use of a different agent) maintenance
therapy is permitted provided there was no
progression after the initial combination. A
switch of agents during treatment for the
management of toxicities is also permitted
provided there was no progression after the initial
combination
OR
b. Subjects must have progressed within 6 months
of completion of a platinum-based adjuvant,
neoadjuvant, or definitive chemotherapy, or
concomitant chemoradiation regimen for locally
advanced disease
7. Subjects with non-squamous cell NSCLC of unknown
EGFR mutation status will require testing (local
laboratory, or central laboratory if local testing is not
available). For subjects with a tumor that harbors an
activating EGFR mutation, acceptable prior therapy is
also defined as a treatment with an EGFR-targeting
tyrosine kinase inhibitor (TKI) given before or after
treatment with a platinum-based combination
chemotherapy as defined above. Subjects with a
tumor that harbors an activating EGFR mutation must
have failed both the platinum-based doublet and the
EGFR-targeting TKI. Treatment with more than
1 EGFR-targeting TKI is acceptable
8. ECOG PS of 0 to 1 at trial entry
9. Estimated life expectancy of more than 12 weeks
10. Adequate hematological function defined by WBC
count ≥ 2.5 × 109
/L with absolute neutrophil count
(ANC) ≥ 1.5 × 109
/L, lymphocyte count ≥ 0.5 ×
109
/L, platelet count ≥ 100 × 109
/L, and hemoglobin
≥ 9 g/dL (may have been transfused)
11. Adequate hepatic function defined by a total bilirubin
level ≤ 1.0 × the upper limit of normal (ULN) range
and aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) levels ≤ 2.5 × ULN for all
subjects
12. Adequate renal function defined by an estimated
creatinine clearance > 30 mL/min according to the
Cockcroft-Gault formula (or local institutional
standard method)
13. Effective contraception for both male and female
subjects if the risk of conception exists (Note: The
effects of the trial drug on the developing human fetus
are unknown; thus, women of childbearing potential
and men must agree to use effective contraception,
defined as 2 barrier methods, or 1 barrier method with
a spermicide, an intrauterine device, or use of oral
female contraceptive. Effective contraception must
be used 30 days prior to first trial drug administration,
for the duration of trial participation, and at least for
60 days after stopping trial participation. Should a
woman become pregnant or suspect she is pregnant
while she or her partner is participating in this trial,
the treating physician should be informed
immediately.)
Exclusion Criteria
Exclusion criteria
1. In the United States only, subjects with a squamous
cell histology will be excluded
2. Systemic anticancer therapy administered after
disease progression during or following a
platinum-based combination, with the following
exception:
Subjects whose disease harbors an activating EGFR
mutation who received an EGFR inhibitor AFTER a
minimum of 2 cycles of first-line platinum-based
therapy. Subjects who tested undetermined or wildtype for EGFR but were previously treated with a TKI
are not eligible unless retested and confirmed to be
activating EGFR mutation positive
3. Subjects with non-squamous cell NSCLC whose
disease harbors an anaplastic lymphoma kinase
(ALK) rearrangement will not be eligible for this trial.
Subjects of unknown ALK status will require testing
for ALK rearrangement (local laboratory, or central
laboratory if local testing is not available) and must
be determined to be ALK wild-type to be eligible for
this trial
4. Prior therapy with any antibody / drug targeting
T-cell coregulatory proteins (immune checkpoints)
such as PD-1, PD-L1, or cytotoxic T-lymphocyte
antigen-4 (CTLA-4). Prior therapy with a cancer
vaccine is acceptable
5. Concurrent anticancer treatment (for example,
cytoreductive therapy, radiotherapy [with the
exception of palliative bone-directed radiotherapy],
immune therapy, or cytokine therapy except for
erythropoietin)
6. Major surgery for any reason, except diagnostic
biopsy, within 4 weeks of randomization and/or if the
subject has not fully recovered from the surgery
within 4 weeks of randomization
7. Subjects receiving immunosuppressive agents (such
as steroids) for any reason should be tapered off these
drugs before initiation of the trial treatment (with the
exception of patients with adrenal insufficiency, who
may continue corticosteroids at physiologic
replacement dose, equivalent to < 10 mg prednisone
daily). Note: Subjects receiving bisphosphonate or
denosumab are eligible provided treatment was
initiated at least 14 days before first dose of trial
treatment
8. All subjects with brain metastases, except those
meeting the following criteria:
a. Brain metastases have been treated locally, and
b. No ongoing neurological symptoms that are
related to the brain localization of the disease
(sequelae that are a consequence of the treatment
of the brain metastases are acceptable)
9. Previous malignant disease (other than NSCLC)
within the last 5 years with the exception of basal or
squamous cell carcinoma of the skin or carcinoma in
situ (bladder, cervical, colorectal, breast)
10. Prior organ transplantation, including allogeneic
stem-cell transplantation
11. Significant acute or chronic infections including,
among others:
Known history of testing positive test for human
immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome
Any positive test for HBV or HCV indicating
acute or chronic infection (test to be conducted
at Screening)
12. Active autoimmune disease that might deteriorate
when receiving an immunostimulatory agent:
a. Subjects with diabetes type I, vitiligo, psoriasis,
hypo- or hyperthyroid disease not requiring
immunosuppressive treatment are eligible
b. Subjects requiring hormone replacement with
corticosteroids are eligible if the steroids are
administered only for the purpose of hormonal
replacement and at doses ≤ 10 mg or 10 mg
equivalent prednisone per day
c. Administration of steroids through a route known
to result in a minimal systemic exposure (topical,
intranasal, intro-ocular, or inhalation) are
acceptable
13. Previous or ongoing administration of systemic
steroids for the management of an acute allergic
phenomenon is acceptable as long as it is anticipated
that the administration of steroids will be completed
in 14 days, or that the daily dose after 14 days will be
≤ 10 mg per day of equivalent prednisone
14. Known severe hypersensitivity reactions to
monoclonal antibodies (Grade ≥ 3 NCI-CTCAE
v 4.03), any history of anaphylaxis, or uncontrolled
asthma (that is, 3 or more features of partially
controlled asthma)
15. History of hypersensitivity reaction to taxanes
16. History of hypersensitivity to Polysorbate 80 that led
to unacceptable toxicity requiring treatment cessation
17. Persisting toxicity related to prior therapy of Grade
> 1 NCI-CTCAE v 4.03 (except neuropathy, see
exclusion criterion #18)
18. Neuropathy ≥ Grade 3
19. Pregnancy or lactation
20. Known alcohol or drug abuse
21. Clinically significant (that is, active) cardiovascular
disease: cerebral vascular accident / stroke
(< 6 months prior to enrollment), myocardial
infarction (< 6 months prior to enrollment), unstable
angina, congestive heart failure (New York Heart
Association Classification Class ≥ II), or serious
cardiac arrhythmia requiring medication
22. All other significant diseases (for example,
inflammatory bowel disease), which, in the opinion of
the Investigator, might impair the subject’s tolerance
of trial treatment
23. Any psychiatric condition that would prohibit the
understanding or rendering of informed consent
24. Vaccination within 4 weeks of the first dose of
avelumab and while on trial is prohibited except for
administration of inactivated vaccines (for
example, inactivated influenza vaccines)
25. Legal incapacity or limited legal capacity
1. In the United States only, subjects with a squamous
cell histology will be excluded
2. Systemic anticancer therapy administered after
disease progression during or following a
platinum-based combination, with the following
exception:
Subjects whose disease harbors an activating EGFR
mutation who received an EGFR inhibitor AFTER a
minimum of 2 cycles of first-line platinum-based
therapy. Subjects who tested undetermined or wildtype for EGFR but were previously treated with a TKI
are not eligible unless retested and confirmed to be
activating EGFR mutation positive
3. Subjects with non-squamous cell NSCLC whose
disease harbors an anaplastic lymphoma kinase
(ALK) rearrangement will not be eligible for this trial.
Subjects of unknown ALK status will require testing
for ALK rearrangement (local laboratory, or central
laboratory if local testing is not available) and must
be determined to be ALK wild-type to be eligible for
this trial
4. Prior therapy with any antibody / drug targeting
T-cell coregulatory proteins (immune checkpoints)
such as PD-1, PD-L1, or cytotoxic T-lymphocyte
antigen-4 (CTLA-4). Prior therapy with a cancer
vaccine is acceptable
5. Concurrent anticancer treatment (for example,
cytoreductive therapy, radiotherapy [with the
exception of palliative bone-directed radiotherapy],
immune therapy, or cytokine therapy except for
erythropoietin)
6. Major surgery for any reason, except diagnostic
biopsy, within 4 weeks of randomization and/or if the
subject has not fully recovered from the surgery
within 4 weeks of randomization
7. Subjects receiving immunosuppressive agents (such
as steroids) for any reason should be tapered off these
drugs before initiation of the trial treatment (with the
exception of patients with adrenal insufficiency, who
may continue corticosteroids at physiologic
replacement dose, equivalent to < 10 mg prednisone
daily). Note: Subjects receiving bisphosphonate or
denosumab are eligible provided treatment was
initiated at least 14 days before first dose of trial
treatment
8. All subjects with brain metastases, except those
meeting the following criteria:
a. Brain metastases have been treated locally, and
b. No ongoing neurological symptoms that are
related to the brain localization of the disease
(sequelae that are a consequence of the treatment
of the brain metastases are acceptable)
9. Previous malignant disease (other than NSCLC)
within the last 5 years with the exception of basal or
squamous cell carcinoma of the skin or carcinoma in
situ (bladder, cervical, colorectal, breast)
10. Prior organ transplantation, including allogeneic
stem-cell transplantation
11. Significant acute or chronic infections including,
among others:
Known history of testing positive test for human
immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome
Any positive test for HBV or HCV indicating
acute or chronic infection (test to be conducted
at Screening)
12. Active autoimmune disease that might deteriorate
when receiving an immunostimulatory agent:
a. Subjects with diabetes type I, vitiligo, psoriasis,
hypo- or hyperthyroid disease not requiring
immunosuppressive treatment are eligible
b. Subjects requiring hormone replacement with
corticosteroids are eligible if the steroids are
administered only for the purpose of hormonal
replacement and at doses ≤ 10 mg or 10 mg
equivalent prednisone per day
c. Administration of steroids through a route known
to result in a minimal systemic exposure (topical,
intranasal, intro-ocular, or inhalation) are
acceptable
13. Previous or ongoing administration of systemic
steroids for the management of an acute allergic
phenomenon is acceptable as long as it is anticipated
that the administration of steroids will be completed
in 14 days, or that the daily dose after 14 days will be
≤ 10 mg per day of equivalent prednisone
14. Known severe hypersensitivity reactions to
monoclonal antibodies (Grade ≥ 3 NCI-CTCAE
v 4.03), any history of anaphylaxis, or uncontrolled
asthma (that is, 3 or more features of partially
controlled asthma)
15. History of hypersensitivity reaction to taxanes
16. History of hypersensitivity to Polysorbate 80 that led
to unacceptable toxicity requiring treatment cessation
17. Persisting toxicity related to prior therapy of Grade
> 1 NCI-CTCAE v 4.03 (except neuropathy, see
exclusion criterion #18)
18. Neuropathy ≥ Grade 3
19. Pregnancy or lactation
20. Known alcohol or drug abuse
21. Clinically significant (that is, active) cardiovascular
disease: cerebral vascular accident / stroke
(< 6 months prior to enrollment), myocardial
infarction (< 6 months prior to enrollment), unstable
angina, congestive heart failure (New York Heart
Association Classification Class ≥ II), or serious
cardiac arrhythmia requiring medication
22. All other significant diseases (for example,
inflammatory bowel disease), which, in the opinion of
the Investigator, might impair the subject’s tolerance
of trial treatment
23. Any psychiatric condition that would prohibit the
understanding or rendering of informed consent
24. Vaccination within 4 weeks of the first dose of
avelumab and while on trial is prohibited except for
administration of inactivated vaccines (for
example, inactivated influenza vaccines)
25. Legal incapacity or limited legal capacity
The Estimated Number of Participants
-
Taiwan
12 participants
-
Global
792 participants
