Efficacy and Safety of Pembrolizumab Plus Investigational Agents in Combination With Chemotherapy as First-Line Treatment in Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (MK-3475-B99/ KEYNOTE-B99)

NCT ID: NCT04924101

Last Updated: 2025-07-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

126 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-15

Study Completion Date

2025-06-23

Brief Summary

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The purpose of this study is to evaluate the use of investigational agents (MK-4830, boserolimab (MK-5890) and lenvatinib (MK-7902)) in combination with pembrolizumab (MK-3475) and etoposide/platinum chemotherapy for the first-line treatment of participants with extensive-stage small cell Lung Cancer (ES-SCLC). No formal hypothesis testing will be performed for this study.

Detailed Description

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Conditions

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Small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pembrolizumab + MK-4830 + Chemotherapy

Participants receive pembrolizumab 200 mg IV infusion on Day 1 of each cycle (cycle length = 3 weeks) every 3 weeks (Q3W) up to 35 administrations (up to approximately 2 years) or until disease progression (PD) or discontinuation, MK-4830 800 mg IV infusion on Day 1 of each cycle Q3W, up to 35 administrations (up to approximately 2 years) or until PD or discontinuation; etoposide 100 mg/m\^2 on Days 1, 2, 3 of each cycle for up to 4 cycles (up to approximately 12 weeks) and cisplatin 75 mg/m\^2 or carboplatin AUC 5 mg/ml/min IV, Day 1 of each cycle Q3W up to 4 cycles (up to approximately 12 weeks) or until PD or discontinuation.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

IV infusion

MK-4830

Intervention Type BIOLOGICAL

IV infusion

Etoposide

Intervention Type DRUG

IV infusion

Cisplatin

Intervention Type DRUG

IV infusion

Carboplatin

Intervention Type DRUG

IV infusion

Pembrolizumab + Boserolimab + Chemotherapy

Participants receive pembrolizumab 200 mg IV infusion on Day 1 of each cycle Q3W up to 35 administrations (up to approximately 2 years) or until PD or discontinuation, boserolimab 30 mg IV infusion on Day 1 of each cycle (cycle length = 6 weeks) every 6 weeks (Q6W), up to 18 administrations (up to approximately 2 years) or until PD or discontinuation; etoposide 100 mg/m\^2 on Days 1, 2, 3 of each cycle for up to 4 cycles (up to approximately 12 weeks) and cisplatin 75 mg/m\^2 or carboplatin AUC 5 mg/ml/min IV, Day 1 of each cycle Q3W up to 4 cycles (up to approximately 12 weeks) or until PD or discontinuation.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

IV infusion

Boserolimab

Intervention Type BIOLOGICAL

IV infusion

Etoposide

Intervention Type DRUG

IV infusion

Cisplatin

Intervention Type DRUG

IV infusion

Carboplatin

Intervention Type DRUG

IV infusion

Pembrolizumab + Lenvatinib + Chemotherapy

Participants receive pembrolizumab 200 mg IV infusion on Day 1 of each 3 week cycle (Q3W) up to 35 administrations (up to approximately 2 years) or until PD or discontinuation, lenvatinib 8 mg once daily (QD) orally up to Cycles 1-4 cycles and up to 20 mg QD orally for Cycles 5-31 or until PD or discontinuation; etoposide 100 mg/m\^2 on Days 1, 2, 3 of each cycle for up to 4 cycles (up to approximately 12 weeks) and cisplatin 75 mg/m\^2 or carboplatin AUC 5 mg/ml/min IV, Day 1 of each cycle Q3W up to 4 cycles (up to approximately 12 weeks) or until PD or discontinuation.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

IV infusion

Lenvatinib

Intervention Type DRUG

Oral capsule

Etoposide

Intervention Type DRUG

IV infusion

Cisplatin

Intervention Type DRUG

IV infusion

Carboplatin

Intervention Type DRUG

IV infusion

Interventions

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Pembrolizumab

IV infusion

Intervention Type BIOLOGICAL

MK-4830

IV infusion

Intervention Type BIOLOGICAL

Boserolimab

IV infusion

Intervention Type BIOLOGICAL

Lenvatinib

Oral capsule

Intervention Type DRUG

Etoposide

IV infusion

Intervention Type DRUG

Cisplatin

IV infusion

Intervention Type DRUG

Carboplatin

IV infusion

Intervention Type DRUG

Other Intervention Names

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KEYTRUDA® MK-3475 SCH 900475 MK-5890 LENVIMA® KISPLYX® MK-7902 E7080 Etopophos® Vepesid® Toposar® VP-16 Etoposide phosphate Platinol-AQ Platinol CDDP Paraplatin Paraplatin NovaPlus Carboplatin N+ Novaplus Carboplatin Novaplus PremierPro Rx Carboplatin

Eligibility Criteria

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Inclusion Criteria

* Has histologically or cytologically confirmed diagnosis of extensive-stage small cell lung cancer (ES-SCLC) in need of first-line therapy
* Has ES-SCLC defined as Stage IV (T any, N any, M1a/b/c) by the American Joint Committee on Cancer, Eighth Edition
* Male participants are eligible to participate if they agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows: Lenvatinib (7 days); Etoposide, Cisplatin, or Carboplatin (180 days) and Pembrolizumab, MK-4830, or (no contraception measures); refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent or must agree to use contraception per protocol unless confirmed to be azoospermic
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman/women of childbearing potential (WOCBP) or is a WOCBP and uses a contraceptive method that is highly effective with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows: Lenvatinib (30 days), Etoposide, Cisplatin, or Carboplatin (180 days), and Pembrolizumab, MK-4830, or Boserolimab (120 days)
* A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours (urine test) or 72 hours (serum test) before the first dose of study intervention
* Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention
* Has measurable disease per RECIST 1.1 as assessed by local site investigator/radiology and verified by blinded independent central review (BICR)
* Submits an archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated where such sample exist
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days before randomization
* Has adequate organ function within 10 days before the first dose of study intervention
* Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg with no changes in antihypertensive medications within 1 week before randomization

Exclusion Criteria

* Has had major surgery within 3 weeks before first dose of study interventions
* Has a preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
* Has urine protein ≥1 g/24 hours
* Has a left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multiple gated acquisition (MUGA) or echocardiogram (ECHO)
* Prolongation of QT interval with Fridericia's correction (QTcF) interval to \>480 ms
* Has clinically significant cardiovascular disease or major arterial thromboembolic event within 12 months before first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
* Has active hemoptysis within 3 weeks before the first dose of study intervention
* Has gastrointestinal malabsorption or any other condition that might affect oral study intervention absorption
* Has serious nonhealing wound, ulcer, or bone fracture within 28 days before first dose of study intervention
* Has any major hemorrhage or venous thromboembolic events within 3 months before the first dose of study intervention. Participants with venous thrombosis diagnosed more than 3 months before the first dose of study intervention must be on stable doses of anticoagulants
* Has a history of inflammatory bowel disease
* Has a history of a gastrointestinal perforation within 6 months before the first dose of study intervention
* Is considered a poor medical risk due to a serious, uncontrolled medical disorder or nonmalignant systemic disease
* Has received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
* Has received prior treatment (chemotherapy, radiotherapy, or surgical resection) including investigational agents for SCLC
* Is expected to require any other form of antineoplastic therapy for SCLC, including radiation therapy, while on study
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
* Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation. A participant that meets this exclusion criterion but is otherwise deemed eligible for the study may be randomized across the specific intervention groups.
* Has symptomatic ascites, pleural effusion, or pericardial effusion. A participant who is clinically stable following treatment for these conditions is eligible
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with brain metastases may participate only if they satisfy all of the following: a) Completed treatment at least 14 days before the first dose of study intervention b) Have no evidence of new or enlarging brain metastases confirmed by posttreatment repeat brain imaging performed at least 4 weeks after pretreatment brain imaging, and c) Are neurologically stable without the need for steroids for at least 7 days before the first dose of study intervention as per local site assessment. Participants with untreated brain metastases will be allowed if they are asymptomatic, the investigator determines there is no immediate CNS-specific treatment required, there is no significant surrounding edema, and the brain metastases are of 5 mm or less in size and 3 or fewer in number
* Has a history of severe hypersensitivity reaction to any study intervention and/or any of its excipients
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has a known history of, or active, neurologic paraneoplastic syndrome
* Has an active infection requiring systemic therapy
* Has a known history of human immunodeficiency virus (HIV) infection and/or Hepatitis B virus infection or an active Hepatitis C infection
* Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
* Has had an allogenic tissue/solid organ transplant
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Banner MD Anderson Cancer Center ( Site 0102)

Gilbert, Arizona, United States

Site Status

University of Colorado Anschutz Medical Campus ( Site 0104)

Aurora, Colorado, United States

Site Status

Georgia Cancer Specialists ( Site 0106)

Atlanta, Georgia, United States

Site Status

Parkview Research Center at Parkview Regional Medical Center ( Site 0130)

Fort Wayne, Indiana, United States

Site Status

Baptist Health Lexington-Research ( Site 0108)

Lexington, Kentucky, United States

Site Status

MFSMC-HJWCI-Oncology Research ( Site 0128)

Baltimore, Maryland, United States

Site Status

Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0122)

Omaha, Nebraska, United States

Site Status

Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0129)

Omaha, Nebraska, United States

Site Status

Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 0114)

Mineola, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center ( Site 0115)

New York, New York, United States

Site Status

Cleveland Clinic-Taussig Cancer Center ( Site 0116)

Cleveland, Ohio, United States

Site Status

UPMC Hillman Cancer Center ( Site 0127)

Pittsburgh, Pennsylvania, United States

Site Status

St Francis Cancer Center-Research Office ( Site 0117)

Greenville, South Carolina, United States

Site Status

Virginia Cancer Institute ( Site 0119)

Richmond, Virginia, United States

Site Status

Klinik Penzing-2. Lungenabteilung ( Site 2101)

Vienna, Vienna, Austria

Site Status

Klinik Floridsdorf-Abteilung für Innere Medizin und Pneumologie ( Site 2100)

Vienna, , Austria

Site Status

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 2003)

Hamilton, Ontario, Canada

Site Status

Kingston Health Sciences Centre-Kingston General Hospital Site ( Site 2005)

Kingston, Ontario, Canada

Site Status

St. Marys Hospital Center ( Site 2000)

Montreal, Quebec, Canada

Site Status

Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 2800)

Szolnok, Jász-Nagykun-Szolnok, Hungary

Site Status

Országos Korányi Pulmonológiai Intézet-XIV. Tüdöbelgyógyászat ( Site 2806)

Budapest, Pest County, Hungary

Site Status

Torokbalint Tudogyogyintezet-Onkopulmonologiai Jarobeteg Centrum ( Site 2801)

Törökbálint, Pest County, Hungary

Site Status

Zala Megyei Szent Rafael Kórház-Pulmonológia ( Site 2805)

Zalaegerszeg, Zala County, Hungary

Site Status

Semmelweis University-Pulmonológiai Klinika ( Site 2802)

Budapest, , Hungary

Site Status

Rambam Health Care Campus-Oncology ( Site 2600)

Haifa, , Israel

Site Status

Shaare Zedek Medical Center ( Site 2602)

Jerusalem, , Israel

Site Status

Meir Medical Center ( Site 2601)

Kfar Saba, , Israel

Site Status

Rabin Medical Center-Oncology ( Site 2604)

Petah Tikva, , Israel

Site Status

Sheba Medical Center-ONCOLOGY ( Site 2603)

Ramat Gan, , Israel

Site Status

Ospedale San Raffaele-Oncologia Medica ( Site 2303)

Milan, Lombardy, Italy

Site Status

ospedale le scotte-U.O.C. Immunoterapia Oncologica ( Site 2300)

Siena, Tuscany, Italy

Site Status

Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Toracica ( Site 2304)

Milan, , Italy

Site Status

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier

Warsaw, Masovian Voivodeship, Poland

Site Status

Samodzielny Publiczny Zespó Grulicy i Chorób Puc w Olsztynie-Oddzial Onkologii z Pododdzialem Chemi

Olsztyn, Warmian-Masurian Voivodeship, Poland

Site Status

Krasnoyarsk Regional Oncology Dispensary, Named after Krizhanovsky ( Site 2708)

Krasnoyarsk, Krasnoyarsk Krai, Russia

Site Status

GBUZ "SPb CRPCstmc(o)" ( Site 2705)

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

N.N.Petrov Research Institute of Oncology-Department of Chemotherapy and Innovative Technologies ( S

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

Scientific research institution of oncology named after N.N. Petrov-Thoracic oncology ( Site 2704)

Saint Petersburg, , Russia

Site Status

Seoul National University Bundang Hospital ( Site 1104)

Seongnam, Kyonggi-do, South Korea

Site Status

The Catholic University Of Korea St. Vincent's Hospital ( Site 1106)

Suwon, Kyonggi-do, South Korea

Site Status

Chungbuk National University Hospital ( Site 1107)

Cheongju-si, North Chungcheong, South Korea

Site Status

Seoul National University Hospital ( Site 1101)

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1105)

Seoul, , South Korea

Site Status

Asan Medical Center-Department of Oncology ( Site 1103)

Seoul, , South Korea

Site Status

Samsung Medical Center ( Site 1100)

Seoul, , South Korea

Site Status

Instituto Catalan de Oncologia - Hospital Duran i Reynals ( Site 2403)

L'Hospitalet de Llobregat, Catalonia, Spain

Site Status

Hospital Insular de Gran Canaria ( Site 2402)

Las Palmas de Gran Canaria, Las Palmas, Spain

Site Status

Hospital Universitari Vall d'Hebron-Oncology ( Site 2401)

Barcelona, , Spain

Site Status

Cantonal Hospital St.Gallen-Oncology & Hematology ( Site 2502)

Sankt Gallen, Canton of St. Gallen, Switzerland

Site Status

Countries

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United States Austria Canada Hungary Israel Italy Poland Russia South Korea Spain Switzerland

Related Links

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Other Identifiers

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MK-3475-B99

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-B99

Identifier Type: OTHER

Identifier Source: secondary_id

2023-506538-56-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1293-9965

Identifier Type: REGISTRY

Identifier Source: secondary_id

3475-B99

Identifier Type: -

Identifier Source: org_study_id

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