Safety and Efficacy Study of Investigational Agents as Monotherapy or in Combination With Pembrolizumab (MK-3475) for the Treatment of Extensive-Stage Small Cell Lung Cancer (ES-SCLC) in Need of Second-Line Therapy (MK-3475-B98/KEYNOTE-B98)

NCT04938817 | Recruiting Phase 1 FDA Drug

• 6 other identifiers: 3475-B98MK-3475-B98KEYNOTE-B982023-507687-38-00U1111-1296-56462020-005628-12
• Study Type: interventional
• Target: 110
• Locations: 11 countries
• Sites: 44

Brief Summary

This study is a rolling arm study of investigational agents as monotherapy or in combination with pembrolizumab in participants with anti-programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) refractory ES-SCLC in need of second-line treatment. This study will have 2 parts: an initial safety lead-in to determine safety and tolerability for experimental combinations of investigational agents without an established recommended phase 2 dose (RP2D) followed by an efficacy evaluation. Investigational agents will initiate directly in or be added to the efficacy evaluation after an initial evaluation of safety and tolerability of the investigational agent has been completed in a separate study or in the safety lead-in of this study. If an RP2D for a combination being evaluated in the safety lead-in is established from another study, then the efficacy evaluation may begin at the determined RP2D. There will be no hypothesis testing in this study.

Conditions

Small Cell Lung Carcinoma

Keywords

Programmed Cell Death Receptor 1 (PD-1); Programmed Cell Death Receptor Ligand 1 (PD-L1); Programmed Cell Death Receptor Ligand 2 (PD-L2); PD-1; PDL1; PD-L1; PD-L2

Outcome Measures

Primary Outcomes (4)

• Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)

  DLTs = ≥1 of the following treatment-related toxicities: Grade (G)4 nonhematologic toxicity; G4 hematologic toxicity lasting \>7 days OR G4 platelet count decreased OR G3 platelet count decreased if associated with bleeding; G3 nonhematologic toxicity including G3 fatigue (lasting \>3 days), G3 diarrhea, nausea, vomiting lasting ≥72 hours, G3 rash ≥7 days despite treatment, G3 uncontrolled hypertension; G3/4 nonhematologic laboratory abnormality if requires medical intervention, hospitalization, or persists for \>1 week; G 3/4 febrile neutropenia, alanine aminotransferase, aspartate aminotransferase and/or bilirubin increase; drug-induced liver injury meeting the Hy's law; G4 creatinine increase; G4 electrolyte abnormalities; treatment related adverse event causing study intervention discontinuation during the first 21 days or administration delay \>14 days during the first 21 days; G5 toxicity. The number of participants with ≥1 DLTs in the safety lead-in phase will be presented.

  Up to 21 days in Cycle 1 (Cycle 1 = 21 days)

• Number of Participants Who Experience at Least One Adverse Event (AE)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience at least one AE will be presented.

  Up to approximately 60 months

• Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be presented.

  Up to approximately 60 months

• Objective Response Rate (ORR) 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 that has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.

  Up to approximately 60 months

Secondary Outcomes (2)

• Progression-free Survival (PFS) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)

  Up to approximately 60 months

• Duration of Response (DOR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)

  Up to approximately 60 months

Study Arms (5)

Coformulation Pembrolizumab/Quavonlimab

EXPERIMENTAL

Participants receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg) administered by intravenous (IV) infusion once every 6 weeks (Q6W) for up to 18 infusions (up to approximately 2 years) or until progressive disease or discontinuation.

Biological: coformulation pembrolizumab/quavonlimab

Coformulation Pembrolizumab/Quavonlimab + Lenvatinib

EXPERIMENTAL

Participants receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered by intravenous (IV) infusion once every 6 weeks (Q6W) for up to 18 infusions (up to approximately 2 years) or until progressive disease or discontinuation. Lenvatinib will be administered orally once-daily (QD) until progressive disease or discontinuation.

Biological: coformulation pembrolizumab/quavonlimab; Drug: lenvatinib

Coformulation Pembrolizumab/Quavonlimab + MK-4830

EXPERIMENTAL

Participants receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS MK-4830 800 mg. Pembrolizumab/quavonlimab will be administered by intravenous (IV) infusion once every 6 weeks (Q6W) for up to 18 infusions (up to approximately 2 years) or until progressive disease or discontinuation. MK-4830 will be administered by IV infusion once every 3 weeks (Q3W) for up to 36 infusions (up to approximately 2 years) or until progressive disease or discontinuation.

Biological: coformulation pembrolizumab/quavonlimab; Biological: MK-4830

Coformulation Favezelimab/Pembrolizumab

EXPERIMENTAL

Participants receive favezelimab/pembrolizumab (coformulation of favezelimab 800 mg and pembrolizumab 200 mg) administered by intravenous (IV) infusion once every 3 weeks (Q3W) for up to 36 infusions (up to approximately 2 years) or until progressive disease or discontinuation.

Biological: coformulation favezelimab/pembrolizumab

R-DXd

EXPERIMENTAL

Participants receive 5.6 mg/kg R-DXd via IV infusion every three weeks (Q3W) until progressive disease or discontinuation.

Biological: R-DXd

Interventions

R-DXd BIOLOGICAL

IV Infusion

R-DXd

coformulation pembrolizumab/quavonlimab BIOLOGICAL

Intravenous (IV) infusion

Also known as: MK-1308A

Coformulation Pembrolizumab/Quavonlimab; Coformulation Pembrolizumab/Quavonlimab + Lenvatinib; Coformulation Pembrolizumab/Quavonlimab + MK-4830

lenvatinib DRUG

Oral administration

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

Coformulation Pembrolizumab/Quavonlimab + Lenvatinib

MK-4830 BIOLOGICAL

IV infusion

Coformulation Pembrolizumab/Quavonlimab + MK-4830

coformulation favezelimab/pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-4280A

Coformulation Favezelimab/Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Arms A-E:
• Has histologically or cytologically confirmed diagnosis of ES-SCLC in need of second-line therapy
• Has progressed on or after treatment with an anti-programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) monoclonal antibody (mAb) administered as part of first-line platinum-based systemic therapy for ES-SCLC
• Has ES-SCLC defined as Stage IV (T any, N any, M1a/b/c) by the American Joint Committee on Cancer, Eighth Edition
• Has received 1 prior line of systemic therapy for small cell lung cancer (SCLC)
• If a woman of childbearing potential (WOCBP), participant must have a negative highly sensitive pregnancy test within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study treatment
• Has measurable disease per RECIST 1.1 as assessed by local site investigator/radiology and verified by BICR
• Has submitted an archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before allocation/randomization
• Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization
• Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
• Has a predicted life expectancy of \>3 months
• Arms A-D:
• Male participants must be abstinent from heterosexual intercourse or agree to use contraception during treatment for at least 7 days after the last dose of lenvatinib. No contraception is required if the participant is receiving pembrolizumab, pembrolizumab/quavonlimab, MK-4830, or favezelimab/pembrolizumab
• Female participants are not pregnant or breastfeeding and are not a WOCBP or if are a WOCBP, are abstinent from heterosexual intercourse or are using contraception during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, MK-4830, or favezelimab/pembrolizumab or 30 days after the last dose of lenvatinib, whichever occurs last

You may not qualify if:

• Arms A-E:
• Has received prior systemic anticancer therapy including investigational agents within 4 weeks before start of study treatment
• Has received prior radiotherapy within 2 weeks of start of study treatment
• Has received lung radiation therapy \>30 Gray (Gy) within 6 months before the first dose of study treatment
• Has received a live or live attenuated vaccine within 30 days before the first dose of study treatment
• 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: completed treatment (e.g., whole brain radiation treatment, stereotactic radiosurgery, or equivalent) ≥14 days before the first dose of study intervention; have no evidence of new or enlarging brain metastases confirmed by post-treatment repeat brain imaging (using the same modality) performed ≥4 weeks after pretreatment brain imaging; and are neurologically stable without the need for steroids for ≥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 millimeter (mm) or less in size and 3 or less in number.
• Has a history of severe hypersensitivity reaction (≥Grade 3) to any study treatment and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid)
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Arms A-D:
• Has had major surgery within 3 weeks before first dose of study treatment
• Has a preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Daiichi Sankyo: collaborator

Study Sites (48)

Banner MD Anderson Cancer Center ( Site 0152)

Gilbert, Arizona, 85234, United States

COMPLETED

Northside Hospital-Northside Hospital Oncology Network ( Site 0156)

Atlanta, Georgia, 30342, United States

COMPLETED

Parkview Research Center at Parkview Regional Medical Center ( Site 0180)

Fort Wayne, Indiana, 46845, United States

COMPLETED

Baptist Health Lexington-Research ( Site 0158)

Lexington, Kentucky, 40503, United States

COMPLETED

University of Kentucky Chandler Medical Center-Medical Oncology ( Site 0157)

Lexington, Kentucky, 40536, United States

COMPLETED

MFSMC-HJWCI-Oncology Research ( Site 0178)

Baltimore, Maryland, 21237, United States

COMPLETED

Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0172)

Omaha, Nebraska, 68130, United States

COMPLETED

Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0179)

Omaha, Nebraska, 68130, United States

COMPLETED

Cleveland Clinic-Taussig Cancer Center ( Site 0166)

Cleveland, Ohio, 44195, United States

COMPLETED

UPMC Hillman Cancer Center ( Site 0177)

Pittsburgh, Pennsylvania, 15232, United States

COMPLETED

St Francis Cancer Center-Research Office ( Site 0167)

Greenville, South Carolina, 29607, United States

COMPLETED

Virginia Cancer Institute ( Site 0169)

Richmond, Virginia, 23229, United States

ACTIVE NOT RECRUITING

Westmead Hospital-Department of Medical Oncology ( Site 4004)

Westmead, New South Wales, 2145, Australia

COMPLETED

The Prince Charles Hospital-Oncology Clinical Trials ( Site 4003)

Brisbane, Queensland, 4032, Australia

COMPLETED

Monash Health-Oncology Research ( Site 4005)

Clayton, Victoria, 3168, Australia

COMPLETED

Hollywood Private Hospital-Medical Oncology ( Site 4001)

Perth, Western Australia, 6009, Australia

RECRUITING

Standort Penzing der Klinik Ottakring-Abteilung für Atemwegs-und Lungenkrankheiten ( Site 3101)

Vienna, 1140, Austria

RECRUITING

Klinik Floridsdorf-Abteilung für Innere Medizin und Pneumologie ( Site 3100)

Vienna, 1210, Austria

RECRUITING

Cross Cancer Institute ( Site 3004)

Edmonton, Alberta, T6G 1Z2, Canada

COMPLETED

Princess Margaret Cancer Centre ( Site 3003)

Toronto, Ontario, M5G 2M9, Canada

COMPLETED

St. Marys Hospital Center ( Site 3000)

Montreal, Quebec, H3T 1M5, Canada

COMPLETED

Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 3800)

Szolnok, Jász-Nagykun-Szolnok, 5004, Hungary

COMPLETED

Rambam Health Care Campus-Oncology ( Site 3600)

Haifa, 3109601, Israel

RECRUITING

Shaare Zedek Medical Center-Oncology ( Site 3602)

Jerusalem, 9103102, Israel

RECRUITING

Meir Medical Center. ( Site 3601)

Kfar Saba, 4428164, Israel

RECRUITING

Rabin Medical Center-Oncology ( Site 3604)

Petah Tikva, 4941492, Israel

RECRUITING

Sheba Medical Center-ONCOLOGY ( Site 3603)

Ramat Gan, 5265601, Israel

RECRUITING

Humanitas-U.O di Oncologia medica ed Ematologia ( Site 3301)

Rozzano, Milano, 20089, Italy

RECRUITING

ospedale le scotte-U.O.C. Immunoterapia Oncologica ( Site 3300)

Siena, Tuscany, 53100, Italy

RECRUITING

Ospedale San Raffaele-Oncologia Medica ( Site 3303)

Milan, 20132, Italy

COMPLETED

Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Toracica ( Site 3304)

Milan, 20141, Italy

RECRUITING

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier ( Site 3900)

Warsaw, Masovian Voivodeship, 02-781, Poland

RECRUITING

Warminsko-Mazurskie Centrum Chorob Płuc w Olsztynie ( Site 3903)

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

COMPLETED

Krasnoyarsk Regional Oncology Dispensary, Named after Krizhanovsky ( Site 3708)

Krasnoyarsk, Krasnoyarsk Krai, 660133, Russia

COMPLETED

Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 3702)

Saint Petersburg, Leningradskaya Oblast', 198255, Russia

COMPLETED

GBUZ LOKB-Oncology department #1 ( Site 3701)

Saint Petersburg, Sankt-Peterburg, 194291, Russia

COMPLETED

GBUZ "SPb CRPCstmc(o)" ( Site 3705)

Saint Petersburg, Sankt-Peterburg, 197758, Russia

COMPLETED

N.N.Petrov Research Institute of Oncology-Department of Chemotherapy and Innovative Technologies ( Site 3703)

Saint Petersburg, Sankt-Peterburg, 197758, Russia

COMPLETED

Scientific research institution of oncology named after N.N. Petrov-Thoracic oncology ( Site 3704)

Saint Petersburg, 197758, Russia

COMPLETED

Seoul National University Bundang Hospital-Medical Oncology ( Site 4104)

Seongnam, Kyonggi-do, 13620, South Korea

RECRUITING

Chungbuk National University Hospital ( Site 4106)

Cheongju-si, North Chungcheong, 28644, South Korea

RECRUITING

Seoul National University Hospital ( Site 4101)

Seoul, 03080, South Korea

COMPLETED

Asan Medical Center-Lung Cancer Center ( Site 4103)

Seoul, 05505, South Korea

COMPLETED

Samsung Medical Center ( Site 4100)

Seoul, 06351, South Korea

RECRUITING

Instituto Catalan de Oncologia - Hospital Duran i Reynals ( Site 3403)

L'Hospitalet de Llobregat, Catalonia, 08908, Spain

RECRUITING

Hospital Universitari Vall d'Hebron-Oncology ( Site 3401)

Barcelona, 08035, Spain

RECRUITING

Hospital Clinic de Barcelona ( Site 3404)

Barcelona, 08036, Spain

RECRUITING

Cantonal Hospital St.Gallen-Oncology & Hematology ( Site 3502)

Sankt Gallen, Canton of St. Gallen, 9000, Switzerland

ACTIVE NOT RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

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

Interventions

lenvatinib; pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2021
• First Posted: June 24, 2021
• Study Start: August 19, 2021
• Primary Completion (Estimated): December 10, 2029
• Study Completion (Estimated): December 10, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

IL (5); KR (5); CH (1); ES (3); PL (2); IT (4); HU (1); AU (2); US (12); CA (3); RU (6)