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Clinical Trials List

Protocol NumberMS200647-0037
NCT Number(ClinicalTrials.gov Identfier)NCT03631706

2018-12-15 - 2022-09-27

Phase II

Not yet recruiting1

Recruiting3

ICD-10C34

Malignant neoplasm of bronchus and lung

ICD-9162.9

Malignant neoplasm of bronchus and lung, unspecified

An Adaptive Phase III, Multicenter, Randomized, Open-Label, Controlled Study of M7824 (Bintrafusp Alfa) Versus Pembrolizumab as a First-line Treatment in Patients With PD-L1 Expressing Advanced Non-small Cell Lung Cancer

  • Trial Applicant

    IQVIA RDS Taiwan Ltd.

  • Sponsor

    Merck KGaA

  • Trial scale

    Multi-Regional Multi-Center

  • Update

    2025/08/20

Investigators and Locations

Principal Investigator Chia-I Shen Division of Thoracic Medicine
Taipei Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

1 Recruiting

Audit

None

Principal Investigator TSUNG -YING YANG Division of Thoracic Medicine
Taichung Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Not yet recruiting

Principal Investigator 蔡鎮良 Division of Thoracic Medicine
Tri-Service General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator James Chih-Hsin Yang Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Audit

None

Condition/Disease

Non-small Cell Lung Cancer

Objectives

Primary  To evaluate whether M7824 improves ORR compared with pembrolizumab in first-line participants with, advanced NSCLC with high PD-L1 tumor expression  To evaluate whether M7824 improves PFS compared with pembrolizumab in first-line participants with advanced NSCLC with high PD-L1 tumor expression Secondary  Safety To evaluate the safety and tolerability of M7824 compared with pembrolizumab  Efficacy To evaluate whether M7824 improves overall survival time compared with pembrolizumab - ORR assessed by Investigators - PFS assessed by Investigators - DOR  PK To characterize PK profile of M7824  Immunogenicity To characterize the immunogenicity of M7824

Test Drug

M7824

Active Ingredient

M7824(MSB0011359C)

Dosage Form

Sterile concentrate solution for infusion

Dosage

10 mg/mL, 60 mL/vial

Endpoints

Primary Outcome Measures :
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) assessed by Independent Review Committee (IRC) [ Time Frame: Time from randomization to planned final assessment at approximately up to 60 months ]
Overall survival (OS) [ Time Frame: Randomization to approximately up to 60 months ]

Secondary Outcome Measures :
Occurrences of Treatment-emergent Adverse Events (TEAEs) and Treatment-related AEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 [ Time Frame: Randomization up to the last safety follow-up visit at approximately up to 60 months ]
Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee [ Time Frame: Time from randomization to planned final assessment expected at up to 60 months ]
Duration of Response Assessed from Complete Response (CR) or Partial Response (PR) according to RECIST 1.1 Assessed by Independent Review Committee [ Time Frame: Time from CR or PR to planned assessment, expected at approximately up to 60 months ]
Concentration of M7284 at the end of Infusion (Ceoi) [ Time Frame: Pre-dose, 30 minutes post-dose at Week 1, 3, 5, 7 and 6 weekly during treatment up to safety follow-up visit (28 days after last dose, assessed up to approximately 60 months) ]
Concentration of M7284 at the end of the Dosing Interval (C trough) [ Time Frame: Pre-dose, 30 minutes post-dose at Week 1, 3, 5, 7 and 6 weekly during treatment up to safety follow-up visit (28 days after last dose, assessed up to approximately 60 months) ]
Immunogenicity as measured by Anti-drug Antibodies Concentration [ Time Frame: Randomization up to safety follow-up visit (28 days post last-dose of study drug administration, assessed up to approximately 60 months) ]

Inclution Criteria

Inclusion Criteria
Participants are eligible to be included in the study only if all the following criteria apply:
Age
1. Are ≥ 18 years of age inclusive, at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2. Are participants who have a histologically confirmed diagnosis of advanced NSCLC and:
a. Have not received prior systemic therapy treatment for their advanced/Stage IV
NSCLC. Completion of treatment with cytotoxic chemotherapy, biological therapy,
and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy
was completed at least 6 months prior to the diagnosis of metastatic disease.
Confirmation of resolution of toxic effects of previous neoadjuvant/adjuvant
chemotherapy therapy to Grade ≤ 1. For radiation toxicity or prior major surgeries,
participants should have recovered from side effects and/or complications.
b. Have measurable disease based on RECIST 1.1
c. Have a life expectancy of at least 3 months
d. Availability of either tumor archival material (< 6 months old) or fresh biopsies
collected within 28 days (excluding bone biopsies) before the first dose is mandatory
to determine PD-L1 expression level prior to enrollment. If participant received local
therapy (ie, radiation therapy [RT] or chemoradiotherapy [CRT]) after the archival
biopsy was taken, a fresh biopsy will be required prior to study entry. Archival
material is formalin fixed tumor tissue sample from a biopsy of a tumor lesion either at
the time of or after the diagnosis of metastatic disease has been made AND from a site
not previously irradiated. Biopsies obtained PRIOR to the administration of any
systemic therapy administered for the treatment of a participant’s tumor (such as
neoadjuvant/adjuvant therapy) will not be permitted for analysis. Fine needle aspirates,
endobronchial ultrasound (EBUS), or cell blocks are not acceptable. Needle or
excisional biopsies, or resected tissue is required.
e. PD-L1 high status is required. PD-L1 high tumors are defined as having ≥ 80% PD-L1
positive tumor cells by the 73-10 assay Participants with a prior test of TPS ≥ 50% as
determined by the PD-L1 IHC 22C3 pharmDx assay performed according to local
laboratory regulations are allowed. In all cases, tumor material must be provided as
specified and must have been evaluated from tissue which is < 6 months old. The
tissue sample must be evaluated by the central vendor prior to randomization
(validation of tissue typically occurs within 5 business days). In case a tumor specimen
is assessed as not evaluable for PD-L1 expression by the central laboratory, if an
additional tumor specimen is submitted AND evaluable for PD-L1 expression, the
participant will be eligible to participate if PD-L1 expression is assessed as “high” by
the central laboratory.
f. See Section 5.2 for exclusion criteria for participants with EGFR, ALK, ROS1, or
BRAF V600E mutation.
3. ECOG PS of 0 to 1 at study entry and date of first dose
4. Have adequate organ function as indicated by the following laboratory values
a. Adequate hematological function defined by absolute neutrophil count (ANC)
≥ 1.5 × 109
/L, platelet count ≥ 100 × 109
/L, and hemoglobin ≥ 9 g/dL
b. Adequate hepatic function defined by a total bilirubin level ≤ the upper limit of normal
(ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels
≤ 1.5 × ULN and alkaline phosphatase ≤ 2.5 ULN. For participants with liver
involvement in their tumor, AST ≤ 5.0 × ULN, ALT ≤ 5.0 × ULN, and bilirubin
≤ 3.0 × ULN is acceptable
c. Adequate renal function defined by creatinine ≤ 1.5× ULN or calculated creatinine
clearance (CrCL) ≥ 30 mL/min for participant with Creatinine > 1.5× ULN
(glomerular filtration rate [GFR] can also be used)
Note: CrCL should be calculated per institutional standard. If no local guideline is
available, CrCL should be calculated using the Cockcroft-Gault Method:
CrCL = ([140-age] × weight [kg] × [0.85 for females only]) / (72 × creatinine)
d. Adequate coagulation function defined as international normalized ratio (INR) or
prothrombin time (PT) ≤ 1.5× ULN unless the participant is receiving anticoagulant
therapy, and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless the
participant is receiving anticoagulant therapy
Sex
5. Are:
 A male participant must agree to use and to have their female partners use a highly
effective contraception (ie, methods with a failure rate of less than 1% per year) as
detailed in Appendix 3 of this protocol 30 days before the first dose of study
intervention (as appropriate), during the study intervention period, and for at least
4 months after the last dose of study intervention and refrain from donating sperm
during this period.
 A male participant is eligible if they agree to the following during the intervention
period and for at least 90 days (a spermatogenesis cycle) after the last dose of study
intervention.
 Refrain from donating sperm
 Use contraception/barrier as detailed below:
 A male condom and female partner use of an additional highly effective
contraceptive method with a failure rate of < 1% per year as described in
Appendix 3, when having sexual intercourse with a woman of childbearing
potential who is not currently pregnant
 A male condom when engaging in any activity that allows for passage of ejaculate
to another person that may result in pregnancy
 A female is eligible if she is not pregnant (i.e., after a negative serum or highly sensitive
urine pregnancy test), not breastfeeding, and at least one of the following conditions
applies:
a. Is not a woman of childbearing potential (WOCBP), as defined in Appendix 3.
OR
b. Is a WOCBP who agrees to use a highly effective contraceptive method (ie, has a
failure rate of less than 1% per year), as listed in Appendix 3, 30 days before the start
of the first dose of study intervention (as appropriate), during the study intervention
period and for at least 4 months after the last dose of study intervention. Should a
woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, the treating physician should be informed immediately.
Informed Consent
6. Can give signed informed consent, as indicated in Appendix 2 (Study Governance), which
includes compliance with the requirements and restrictions listed in the informed consent
form (ICF) and this protocol.

Exclusion Criteria

Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. The participant’s tumor harbors an EGFR sensitizing (activating) mutation, ALK
translocation, ROS1 rearrangement, or BRAF V600E mutation, if targeted therapy is
locally approved. EGFR sensitizing mutations are those mutations that are amenable to
treatment with tyrosine kinase inhibitors including, but not limited to erlotinib, gefitinib,
afatinib, or osimertinib. Investigators must be able to produce the source documentation
of the EGFR mutation and ALK translocation status in all participants with nonsquamous
histologies AND for participants in whom testing is clinically recommended. ROS1
testing is required in participants with nonsquamous NSCLC, who have had negative
EGFR/ALK testing if targeted therapy is locally approved. If an EGFR sensitizing
mutation, ALK translocation, or ROS1 rearrangement, or BRAF V600E is not detected,
additional information regarding the mutation status of the other molecules is not
required. If unable to test for these molecular changes, formalin fixed paraffin embedded
tumor tissue of any age should be submitted to a central laboratory designated by the
Sponsor for such testing. Participants with nonsquamous histologies will not be
randomized until the EGFR mutation status and/or ALK translocation, ROS1
rearrangement, and/or BRAF V600E mutation (if indicated) status is available in source
documentation at the site. For participants enrolled who are known to have a tumor of
predominantly squamous histology, molecular testing will not be required as this is not
standard of care and is not part of current diagnostic guidelines.
2. Has received major surgery within 4 weeks prior to the first dose of study intervention;
received thoracic RT of > 30 Gy within 6 months prior to the first dose of study
intervention.
3. Previous malignant disease (other than the target malignancy to be investigated in this
study) within the last 3 years. Participants with a history of cervical carcinoma in situ,
superficial or noninvasive bladder cancer, or basal cell or squamous cell carcinoma in situ
previously treated with curative intent are NOT excluded. Participants with other
localized malignancies treated with curative intent need to be discussed with the Medical
Monitor.
4. Has active CNS metastases causing clinical symptoms or metastases that require
therapeutic intervention and/or carcinomatosis meningitis (including leptomeningeal
carcinomatosis) identified either on Baseline brain imaging during the Screening period
OR identified prior to signing the ICF. Participants with a history of treated CNS
metastases (by surgery or RT) are not eligible unless they have fully recovered from
treatment, demonstrate radiographic stability defined as 2 brain images, both of which are
obtained after treatment to the brain metastases. These imaging scans should both be
obtained at least 4 weeks apart and show no evidence of intracranial pressure. In addition,
any neurologic symptoms that developed either as a result of the brain metastases or their
treatment must have returned to baseline or resolved. Any steroids administered as part of
this therapy must be completed at least 3 days prior to study intervention. Participants
with CNS metastases incidentally detected during Screening which do not cause clinical
symptoms and for which standard of care suggests no therapeutic intervention is
indicated should be discussed with the Sponsor Medical Responsible to confirm
eligibility.
5. Active autoimmune disease that has required systemic treatment in past 1 year (ie, with
use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), OR is
receiving systemic steroid therapy < 3 days prior to the first dose of study intervention or
receiving any other form of immunosuppressive medication. Participants requiring
hormone replacement with corticosteroids are eligible if the steroids are administered
only for the purpose of hormonal replacement and at low doses (typically ≤ 10 mg of
prednisone or equivalent per day). Equivalent hydrocortisone doses are also permitted if
administered as a replacement therapy. Corticosteroid use on study as a premedication for
iv contrast allergies/reactions (related to scans) is allowed and must be documented. This
must be discussed with Medical Monitors for clinical indications in which participants
may require a higher dose. Active autoimmune disease that might deteriorate when
receiving an immunostimulatory agent:
a. Participants with diabetes Type I, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid
disease not requiring immunosuppressive treatment are eligible. Consult Medical
Monitor for other autoimmune diseases.
6. Administration of steroids for other conditions through a route known to result in a
minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable
7. Known severe hypersensitivity reactions to mAB (Grade ≥ 3 National Cancer Institute
[NCI] Common Terminology Criteria for Adverse Events [CTCAE] v5.0), or
uncontrolled asthma (ie, 3 or more features of partially controlled asthma)
8. Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but
with the exception of transplants that do not require immunosuppression (eg, corneal
transplant, hair transplant)
9. Has interstitial lung disease (ILD) OR has had a history of pneumonitis that has required
oral or IV steroids
10. Significant acute or chronic infections including, among others:
a. Known history of positive test for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (no testing at Screening required). If an
Investigator has a strong suspicion of HIV infection without known history for a
participant in Screening, however participant refuses testing, discuss with Medical
Monitor to assess eligibility. (Note: HIV testing is not mandated for study inclusion;
however, if it is performed at any point in Screening or while on study, a site must
consent the participant for HIV testing as per local standard guidance.)
b. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (HBV surface
antigen positive and HBV core antibody positive with reflex to positive HBV DNA, or
HBV core antibody positive alone with reflex to positive HBV DNA, or positive HCV
antibody with reflex to positive HCV RNA) at Baseline. Discuss with the Medical
Monitor if history of HBV or HCV infection is known. If medically indicated,
participants infected with HBV must be treated and on a stable dose of antivirals (eg,
entecavir, tenofovir, or lamivudine; adefovir or interferon are not allowed) at study
entry and with planned monitoring and management according to appropriate labeling
guidance. Participants on active HCV therapy at study entry must be on a stable dose
without documented clinically significant impaired liver function test or hematologic
abnormalities (must meet criteria below) and with planned monitoring and
management according to appropriate labeling guidance. HBV and/or HCV viral titers
must be monitored according to Section 1.3 (Schedule of Activities) in these
participants.
c. Participants with active tuberculosis (history of exposure or history of positive
tuberculosis test; plus presence of clinical symptoms, physical, or radiographic
findings)
11. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with participation for the full
duration of the study, or is not in the best interest of the participant, in the opinion of the
treating Investigator
Prior/Concomitant Therapy
12. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or
checkpoint pathways)
13. Is expected to require any other form of systemic or localized antineoplastic therapy
while on study (including maintenance therapy with another agent for NSCLC, RT,
and/or surgical resection)
14. Use of a prohibited concomitant drug, as defined in Section 6.5.2
15. Has received or will receive a live vaccine within 30 days prior to the first administration
of study intervention. Seasonal flu vaccines that do not contain a live virus are permitted.
Contact Medical Monitor if screening extension is needed for participant vaccinated
within 30 days of planned first dose
16. Has an active infection requiring systemic therapy/antibiotics (except as indicated,
discuss alternative scenarios with the Medical Monitor)
Prior/Concurrent Clinical Study Experience
17. Is currently participating and receiving study therapy or has participated in a study of an
investigational agent and received study therapy or used an investigational device within
6 months of the first dose of treatment
Other Exclusions
18. Known active alcohol or drug abuse
19. Any psychiatric condition that would prohibit the understanding or rendering of informed
consent or consistent participation in study procedures
20. Legal incapacity or limited legal capacity.

The Estimated Number of Participants

  • Taiwan

    38 participants

  • Global

    300 participants

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