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Clinical Trials List

Protocol NumberMK3475-604
NCT Number(ClinicalTrials.gov Identfier)NCT03066778

2017-08-07 - 2021-12-31

Phase III

Terminated7

ICD-10C34

Malignant neoplasm of bronchus and lung

A Phase 3 Randomized, Double-Blind, Placebo-controlled Trial of Pembrolizumab (MK-3475/SCH900475) in Combination With Etoposide/Platinum (Cisplatin or Carboplatin) for the First-line Treatment of Subjects With Extensive Stage Small Cell Lung Cancer (KEYNOTE-604)

  • Trial Applicant

    Merck Sharp & Dohme (I.A.) LLC

  • Sponsor

    Merck Sharp & Dohme Corp.

  • Trial scale

    Multi-Regional Multi-Center

  • Update

    2025/08/20

Investigators and Locations

Principal Investigator Yuh-Min Chen Division of Thoracic Medicine
Taipei Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

3 Terminated

Audit

None

Principal Investigator Te-Chun Hsia Division of Thoracic Medicine
China Medical University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Terminated

Principal Investigator Wu-Chou Su Division of Thoracic Medicine
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Terminated

Audit

None

Principal Investigator 黃國棟 Division of Thoracic Medicine
Kaoshiung Chang Gung Memorial Hospital of the C.G.M.F.

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Terminated

Principal Investigator 陳彥勳 Division of Hematology & Oncology
Chi Mei Hospital, Liouying

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Terminated

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

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Terminated

Principal Investigator Te-Chun Hsia 未分科
China Medical University Hospital-Taipei

Co-Principal Investigator

Audit

None

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 Terminated

Audit

None

Condition/Disease

Extensive Stage Small Cell Lung Cancer

Objectives

The purpose of this study is to assess the safety and efficacy of pembrolizumab plus standard of care (SOC) chemotherapy (etoposide/platinum [EP]) in participants with newly diagnosed extensive stage small cell lung cancer (ES-SCLC) who have not previously received systemic therapy for this malignancy.

Test Drug

Keytruda

Active Ingredient

Pembrolizumab

Dosage Form

Injection

Dosage

100

Endpoints

Primary Outcome Measures :
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Through database cutoff of 02-Dec-2019 (up to approximately 30.5 months) ]
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. PD, as determined by RECIST 1.1, was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The PFS was calculated using the non-parametric Kaplan-Meier method for censored data.

Overall Survival (OS) [ Time Frame: Through database cutoff of 02-Dec-2019 (up to approximately 30.5 months) ]
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow up. The OS was calculated using the non-parametric Kaplan-Meier method for censored data.

Secondary Outcome Measures :
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Through database cutoff of 02-Dec-2019 (up to approximately 30.5 months) ]
ORR was defined as the percentage of participants who achieve a best objective response of complete response (CR) or partial response (PR) per RECIST 1.1. CR was defined as the disappearance of all target lesions. PR was defined as ≥30% decrease in the sum of diameters of target lesions taking as a reference the baseline sum diameters. In this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The ORR was calculated using the Miettinen & Nurminen method stratified by type of platinum therapy (carboplatin or cisplatin), baseline ECOG performance status (0 or 1), and baseline LDH (≤ or > upper limit of normal).

Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Through database cutoff of 02-Dec-2019 (up to approximately 30.5 months) ]
DOR was defined as the time from first documented evidence of a Complete Response (CR) or Partial Response (PR) per RECIST 1.1 until progressive disease (PD) per RECIST 1.1 or death due to any cause, whichever occurred first. CR was defined as the disappearance of all target lesions. PR was defined as ≥30% decrease in the sum of diameters of target lesions taking as a reference the baseline sum diameters. PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. In this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data. The DOR for all participants who experienced a CR or PR is presented.

Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Through database cutoff of 02-Dec-2019 (up to approximately 30.5 months) ]
An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have had a causal relationship with this treatment. An adverse event could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an adverse event. The number of participants who experienced an AE was reported for each arm according to the treatment received.

Inclution Criteria

Subject Inclusion Criteria
In order to be eligible for participation in this trial, the subject must:
1. Have a documented new diagnosis of SCLC by histology or cytology from brushing,
washing, or needle aspiration of a defined lesion. Subjects who do not have
histology samples (defined as core or excisional biopsy, or resections) will need to
undergo a new biopsy to provide a tissue sample.
2. Have extensive stage disease defined as Stage IV (T any, N any, M 1a/b) by the
American Joint Committee on Cancer, Seventh Edition.
3. Have at least 1 lesion that meets the criteria for being measurable, as defined by
RECIST 1.1, and is appropriate for selection as a target lesion, as determined by local
site investigator/radiology review. Lesions that appear measurable, but have
undergone palliative irradiation, cannot be target lesions.
4. Have provided archival tumor tissue sample or newly obtained core or excisional
biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffinembedded tissue blocks are preferred to slides.
5. Have ECOG Performance Status of 0 or 1. See Section 12.3 for definitions.
6. Have a life expectancy of at least 3 months.
7. Have adequate organ function as indicated by the following laboratory values
(Table 1):
8. Be ≥18 years of age on day of signing informed consent.
9. If female subject of childbearing potential, have a negative urine or serum pregnancy
test within 72 hours prior to receiving the first dose of study medication. If the urine
test is positive or cannot be confirmed as negative, a serum pregnancy test will be
required.
10. If female and of childbearing potential, be willing to use an adequate method of
contraception as outlined in Section 5.7.2 – Contraception, starting with the first dose
of study medication through 120 days after the last dose of study medication and up
to 180 days after last dose of chemotherapeutic agents.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
for the subject.
11. If male and of childbearing potential, agree to use an adequate method of
contraception as outlined in Section 5.7.2 - Contraception, starting with the first dose
of study medication through 120 days after the last dose of study medication and up
to 180 days after last dose of chemotherapeutic agents.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
for the subject.
12. Have voluntarily agreed to participate by giving written informed consent/assent for
the trial. The subject may also provide consent/assent for Future Biomedical
Research. However, the subject may participate in the main trial without participating
in Future Biomedical Research.

Exclusion Criteria

Subject Exclusion Criteria
The subject must be excluded from participating in the trial if the subject:
1. Has received prior systemic therapy for the treatment of SCLC.
Note: Palliative radiation therapy is allowed until 7 days prior to the first dose of trial
medication, provided that the radiated lesion is clinically stable and the patient is not
receiving steroids for at least 7 days prior to the first dose of study medication. The
radiated lesion must not be a thoracic lesion and must not be included as a target
lesion for RECIST 1.1 measurements.
2. 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 4 weeks of the first dose of treatment for another health-related problem.
Note: Subjects who have entered the follow-up phase of an investigational trial may
participate as long as it has been at least 4 weeks since the last dose of the previous
investigational agent.
3. Is expected to require any other form of antineoplastic therapy for SCLC, including
radiation therapy, while on study.
Note: Patients with PR or CR will be offered PCI therapy at the completion of the
4 cycles of chemotherapy with or without pembrolizumab.
4. Has known active central nervous system metastases and/or carcinomatous
meningitis. Subjects with brain metastases may participate provided they:
 Received treatment (eg, whole brain radiation treatment [WBRT], stereotactic
radiosurgery, or equivalent) at least 14 days prior to the first dose of trial
treatment,
 Have no evidence of new or enlarging brain metastases confirmed by posttreatment repeat brain imaging (using the same modality) performed at least
3 weeks after pre-treatment brain imaging, and
 Are neurologically stable without the need for steroids for at least 7 days before
first dose of trial treatment as per local site assessment.
5. Has had major surgery within 3 weeks prior to receiving the first dose of trial
treatment or has not recovered adequately from toxicity and/or complications from an
intervention prior to receiving the first dose of study treatment.
6. Has a history of non-infectious pneumonitis that required steroids or has current
pneumonitis.
7. Has a known history of interstitial lung disease.
8. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include early stage cancers (carcinoma in situ or Stage 1) treated with
curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin,
in situ cervical cancer, or in situ breast cancer that has undergone potentially curative
therapy.
9. Has active autoimmune disease that has required systemic treatment in the past
2 years (ie, with use of disease-modifying agents, corticosteroids, or
immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency)
is not considered a form of systemic treatment.
10. Has a known history of, or active, neurologic paraneoplastic syndrome.
11. Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal
obstruction, and/or abdominal carcinomatosis.
12. Has a history of a severe hypersensitivity reaction to treatment with another
monoclonal antibody.
13. Is taking chronic systemic steroids (in doses exceeding 10 mg daily of prednisone
equivalent) within 7 days prior to the first dose of trial treatment.
Note: Subjects with asthma or chronic obstructive pulmonary disease that require
intermittent use of bronchodilators, inhaled steroids, or local steroid injections would
not be excluded from the study.
14. Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive
therapy within 7 days prior to the first dose of trial treatment.
15. Has received a live vaccine within 30 days prior to the first dose of trial drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for
injection are generally killed virus vaccines and are allowed; however, intranasal
influenza vaccines (eg, FluMist®
) are live attenuated vaccines and are not allowed.
16. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or
with an agent directed to another co-inhibitory T-cell receptor (ie, CTLA-4, OX-40,
CD137) or has previously participated in a Merck pembrolizumab (MK-3475) clinical
trial.
17. Has severe hypersensitivity (Grade ≥3) to pembrolizumab and/or any of its
excipients.
18. Has an active infection requiring systemic therapy.
19. Has a known history of HIV infection. No HIV testing is required unless mandated
by local health authority.
20. Has a history of or known active Hepatitis B (eg, Hepatitis B surface antigen
[HBsAg] reactive) or Hepatitis C virus (eg, HCV RNA [qualitative] is detected).
Note: HCV RNA testing is not required in those countries where local standard of
care uses only Hepatitis C antibody testing as evidence of status of Hepatitis C.
21. Has a known history of active TB (Bacillus Tuberculosis).
22. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject’s participation
for the full duration of the study, or is not in the best interest of the subject to
participate, in the opinion of the treating investigator.
23. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
24. Has symptomatic ascites or pleural effusion. A subject who is clinically stable
following treatment for these conditions (including therapeutic thoraco - or
paracentesis) is eligible.
25. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study starting with the screening visit through 120 days after
the last dose of trial treatment through and up to 180 days after last dose of
chemotherapeutic agents.

The Estimated Number of Participants

  • Taiwan

    21 participants

  • Global

    430 participants

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