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)

NCT04924101 | Completed Phase 2 FDA Drug

• 5 other identifiers: 3475-B99MK-3475-B99KEYNOTE-B992023-506538-56-00U1111-1293-9965
• Study Type: interventional
• Target: 126
• Locations: 11 countries
• Sites: 49

Brief Summary

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.

Conditions

Small Cell Lung Cancer

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1); Programmed Death-Ligand 2 (PDL2, PD-L2); Pembrolizumab (MK-3475)

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.

  Up to approximately 5 years

• Six-Month Progression-Free Survival (PFS) as Assessed by BICR per RECIST 1.1

  Six-month PFS is defined as the survival without documented disease progression (PD) per RECIST 1.1 by BICR or death due to any cause, whichever occurs first at 6 months after randomization. PD is defined as ≥20% increase in the sum of diameters of target lesions. 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 is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented.

  Up to approximately 6 months

Secondary Outcomes (7)

• Duration of Response (DOR) as Assessed by BICR per RECIST 1.1

  Up to approximately 5 years

• Progression-Free Survival (PFS) as Assessed by BICR per RECIST 1.1

  Up to approximately 5 years

• Overall Survival (OS)

  Up to approximately 5 years

• Percent Change From Baseline in Tumor Size as Assessed by BICR

  Baseline, 5 years

• Number of Participants Who Experienced an Adverse Event (AE)

  Up to approximately 5 years

Study Arms (3)

Pembrolizumab + MK-4830 + Chemotherapy

EXPERIMENTAL

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.

Biological: Pembrolizumab; Biological: MK-4830; Drug: Etoposide; Drug: Cisplatin; Drug: Carboplatin

Pembrolizumab + Boserolimab + Chemotherapy

EXPERIMENTAL

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.

Biological: Pembrolizumab; Biological: Boserolimab; Drug: Etoposide; Drug: Cisplatin; Drug: Carboplatin

Pembrolizumab + Lenvatinib + Chemotherapy

EXPERIMENTAL

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.

Biological: Pembrolizumab; Drug: Lenvatinib; Drug: Etoposide; Drug: Cisplatin; Drug: Carboplatin

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: KEYTRUDA®, MK-3475, SCH 900475

Pembrolizumab + Boserolimab + Chemotherapy; Pembrolizumab + Lenvatinib + Chemotherapy; Pembrolizumab + MK-4830 + Chemotherapy

MK-4830 BIOLOGICAL

IV infusion

Pembrolizumab + MK-4830 + Chemotherapy

Boserolimab BIOLOGICAL

IV infusion

Also known as: MK-5890

Pembrolizumab + Boserolimab + Chemotherapy

Lenvatinib DRUG

Oral capsule

Also known as: LENVIMA®, KISPLYX®, MK-7902, E7080

Pembrolizumab + Lenvatinib + Chemotherapy

Etoposide DRUG

IV infusion

Also known as: Etopophos®, Vepesid®, Toposar®, VP-16, Etoposide phosphate

Pembrolizumab + Boserolimab + Chemotherapy; Pembrolizumab + Lenvatinib + Chemotherapy; Pembrolizumab + MK-4830 + Chemotherapy

Cisplatin DRUG

IV infusion

Also known as: Platinol-AQ, Platinol, CDDP

Pembrolizumab + Boserolimab + Chemotherapy; Pembrolizumab + Lenvatinib + Chemotherapy; Pembrolizumab + MK-4830 + Chemotherapy

Carboplatin DRUG

IV infusion

Also known as: Paraplatin, Paraplatin NovaPlus, Carboplatin N+ Novaplus, Carboplatin Novaplus, PremierPro Rx Carboplatin

Pembrolizumab + Boserolimab + Chemotherapy; Pembrolizumab + Lenvatinib + Chemotherapy; Pembrolizumab + MK-4830 + Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (49)

Banner MD Anderson Cancer Center ( Site 0102)

Gilbert, Arizona, 85234, United States

Location

University of Colorado Anschutz Medical Campus ( Site 0104)

Aurora, Colorado, 80045, United States

Location

Georgia Cancer Specialists ( Site 0106)

Atlanta, Georgia, 30341, United States

Location

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

Fort Wayne, Indiana, 46845, United States

Location

Baptist Health Lexington-Research ( Site 0108)

Lexington, Kentucky, 40503, United States

Location

MFSMC-HJWCI-Oncology Research ( Site 0128)

Baltimore, Maryland, 21237, United States

Location

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

Omaha, Nebraska, 68130, United States

Location

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

Omaha, Nebraska, 68130, United States

Location

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

Mineola, New York, 11501, United States

Location

Memorial Sloan Kettering Cancer Center ( Site 0115)

New York, New York, 10065, United States

Location

Cleveland Clinic-Taussig Cancer Center ( Site 0116)

Cleveland, Ohio, 44195, United States

Location

UPMC Hillman Cancer Center ( Site 0127)

Pittsburgh, Pennsylvania, 15232, United States

Location

St Francis Cancer Center-Research Office ( Site 0117)

Greenville, South Carolina, 29607, United States

Location

Virginia Cancer Institute ( Site 0119)

Richmond, Virginia, 23229, United States

Location

Klinik Penzing-2. Lungenabteilung ( Site 2101)

Vienna, Vienna, 1140, Austria

Location

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

Vienna, 1210, Austria

Location

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 2003)

Hamilton, Ontario, L8V 4X2, Canada

Location

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

Kingston, Ontario, K7L 2V7, Canada

Location

St. Marys Hospital Center ( Site 2000)

Montreal, Quebec, H3T 1M5, Canada

Location

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

Szolnok, Jász-Nagykun-Szolnok, 5004, Hungary

Location

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

Budapest, Pest County, 1121, Hungary

Location

Torokbalint Tudogyogyintezet-Onkopulmonologiai Jarobeteg Centrum ( Site 2801)

Törökbálint, Pest County, 2045, Hungary

Location

Zala Megyei Szent Rafael Kórház-Pulmonológia ( Site 2805)

Zalaegerszeg, Zala County, 8900, Hungary

Location

Semmelweis University-Pulmonológiai Klinika ( Site 2802)

Budapest, 1083, Hungary

Location

Rambam Health Care Campus-Oncology ( Site 2600)

Haifa, 3109601, Israel

Location

Shaare Zedek Medical Center ( Site 2602)

Jerusalem, 9103102, Israel

Location

Meir Medical Center ( Site 2601)

Kfar Saba, 4428164, Israel

Location

Rabin Medical Center-Oncology ( Site 2604)

Petah Tikva, 4941492, Israel

Location

Sheba Medical Center-ONCOLOGY ( Site 2603)

Ramat Gan, 5262100, Israel

Location

Ospedale San Raffaele-Oncologia Medica ( Site 2303)

Milan, Lombardy, 20132, Italy

Location

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

Siena, Tuscany, 53100, Italy

Location

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

Milan, 20141, Italy

Location

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

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

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

Olsztyn, Warmian-Masurian Voivodeship, 10-357, Poland

Location

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

Krasnoyarsk, Krasnoyarsk Krai, 660133, Russia

Location

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

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

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

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

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

Saint Petersburg, 197758, Russia

Location

Seoul National University Bundang Hospital ( Site 1104)

Seongnam, Kyonggi-do, 13620, South Korea

Location

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

Suwon, Kyonggi-do, 16247, South Korea

Location

Chungbuk National University Hospital ( Site 1107)

Cheongju-si, North Chungcheong, 28644, South Korea

Location

Seoul National University Hospital ( Site 1101)

Seoul, 03080, South Korea

Location

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

Seoul, 03722, South Korea

Location

Asan Medical Center-Department of Oncology ( Site 1103)

Seoul, 05505, South Korea

Location

Samsung Medical Center ( Site 1100)

Seoul, 06351, South Korea

Location

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

L'Hospitalet de Llobregat, Catalonia, 08908, Spain

Location

Hospital Insular de Gran Canaria ( Site 2402)

Las Palmas de Gran Canaria, Las Palmas, 35001, Spain

Location

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

Barcelona, 08035, Spain

Location

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

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; lenvatinib; Etoposide; etoposide phosphate; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: June 11, 2021
• Study Start: July 15, 2021
• Primary Completion: June 23, 2025
• Study Completion: June 23, 2025
• Last Updated: July 23, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

CA (3); ES (3); IT (3); HU (5); PL (2); RU (4); KR (7); AU (2); IL (5); US (14); CH (1)