A Study of Pembrolizumab (MK-3475) in Combination With Etoposide/Platinum (Cisplatin or Carboplatin) for Participants With Extensive Stage Small Cell Lung Cancer (MK-3475-604/KEYNOTE-604)
CompletedPhase 3Results postedLast updated 3 October 2022
What this trial tests
Phase 3 trial testing Pembrolizumab in Small Cell Lung Cancer (SCLC) in 453 participants. Completed in 21 September 2021.
18 and older, any sex, with Small Cell Lung Cancer (SCLC). Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
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)Primary· 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. T
Group
Value
95% CI
Pembrolizumab+EP
4.8
4.3 – 5.4
Placebo+EP
4.3
4.2 – 4.5
Overall Survival (OS)Primary· 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 and presented for the first course of study treatment per protocol.
Group
Value
95% CI
Pembrolizumab+EP
10.8
9.2 – 12.9
Placebo+EP
9.7
8.6 – 10.7
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)Secondary· 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
Group
Value
95% CI
Pembrolizumab+EP
70.6
64.2 – 76.4
Placebo+EP
61.8
55.1 – 68.2
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)Secondary· 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 demons
Group
Value
95% CI
Pembrolizumab+EP
NA
NA – NA
Placebo+EP
NA
NA – NA
Number of Participants Who Experienced an Adverse Event (AE)Secondary· 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
Group
Value
95% CI
Pembrolizumab+EP
223
Placebo+EP
222
Number of Participants Discontinuing Study Treatment Due to an Adverse Event (AE)Secondary· Up to approximately 26 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
Group
Value
95% CI
Pembrolizumab+EP
33
Placebo+EP
14
Number of Participants Experiencing Any Grade 3 to 5 Adverse Events (AE) as Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE 4.03)Secondary· Up to approximately 30.5 months
The CTCAE uses Grades 1 through 5 correlating to AE severity criteria. Grade 1=mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2=moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3=severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4=life-threatening consequences; urgent intervention indicated. Grade 5=death related to
Group
Value
95% CI
Pembrolizumab+EP
175
Placebo+EP
172
Change From Baseline at Week 18 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life ScaleSecondary· Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days]) and Week 18
EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores are transformed to a range of 0 to 100 using a standard EORTC algorithm. Change from baseline scores w
Group
Value
95% CI
Pembrolizumab+EP
8.66
5.26 – 12.06
Placebo+EP
4.23
0.93 – 7.52
Time to True Deterioration (TTD) in the Composite Endpoint of Cough, Chest Pain, and Dyspnea Using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and Lung Cancer Module 13 (QLQ-LC13)Secondary· Day 1 of Cycles 1-9, Day 1 of every other cycle for Cycles 10-17 and 30 days after last dose of study treatment (Up to approximately 27 months)
TTD in patient-reported lung cancer symptoms of cough (QLQ-LC-13 Item 1), chest pain (QLQ-LC-13 Item 10), and dyspnea (QLQ-C30 Item 8) was a composite endpoint defined as the time to first onset of ≥10 point deterioration from baseline in an item confirmed by a second adjacent ≥10 point deterioration. The QLQ-LC13 consists of 13 measures of lung cancer symptoms and side effects from chemotherapy and radiation. It is scored on a 4-point scale (1=none, 2=a little, 3=quite a bit, 4=very much). Scores were transformed to a range of 0 to 100 using a standard algorithm. Higher scores represented inc
Group
Value
95% CI
Pembrolizumab+EP
NA
NA – NA
Placebo+EP
8.7
5.9 – NA
Adverse events — posted to ClinicalTrials.gov
Time frame: First Course: Up to 49.5 months Second Course: Up to 37.9 months First and second course dosing occurred concurrently.
Reporting threshold: 5%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
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.
The primary study hypotheses are that pembrolizumab+EP prolongs Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent central review (BICR) and Overall Survival (OS) compared with placebo+EP in adult participants with ES-SCLC. In this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
With protocol Amendment 07 (03-Oct-2018), the outcome measure of "Change from Baseline at Weeks 12 and 24 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale" was replaced with a single time point analysis at Week 18.
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
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NCT07302347 — A Study of Pembrolizumab in Japanese Pediatric Participants With Solid Tumors or Lymphomas and Japanese Adult Participan
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NCT06724042 — Study of ISM5939 in Patients With Advanced and/or Metastatic Solid Tumors
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NCT07383441 — Adding Biotherapy or Placebo to Standard Treatment for Advanced Kidney Cancer
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NCT06745323 — A Phase 2, Open-label, Randomized, Multicenter Study of Tarlatamab Dosing Regimens in Subjects With SCLC
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Trials by the same sponsor.
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Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
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Sponsor: as reported to ClinicalTrials.gov by Merck Sharp & Dohme LLC
Last refreshed: 3 October 2022
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03066778.