Actively Recruiting
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)
Led by Merck Sharp & Dohme LLC · Updated on 2026-05-12
110
Participants Needed
48
Research Sites
433 weeks
Total Duration
On this page
Sponsors
M
Merck Sharp & Dohme LLC
Lead Sponsor
D
Daiichi Sankyo
Collaborating Sponsor
AI-Summary
What this Trial Is About
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
Official Title
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)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Diagnosed with extensive-stage small cell lung cancer (ES-SCLC) confirmed by biopsy or cytology and needing second-line treatment
- Cancer progressed after treatment with anti-PD-1/PD-L1 antibody as part of first-line platinum-based therapy
- ES-SCLC is Stage IV by American Joint Committee on Cancer, Eighth Edition
- Received only one prior systemic therapy for small cell lung cancer
- Women of childbearing potential must have a negative pregnancy test before starting treatment
- Have measurable disease per RECIST 1.1 criteria confirmed by investigators
- Submitted an archival tumor tissue sample or new tumor biopsy not previously irradiated
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before randomization
- Hepatitis B positive participants must have been on antiviral therapy with undetectable viral load
- Hepatitis C participants must have undetectable viral load at screening
- Predicted life expectancy greater than 3 months
- Males in Arms A-D must use contraception or abstain from heterosexual intercourse during treatment and for at least 7 days after last dose of lenvatinib
- Females not pregnant or breastfeeding; women of childbearing potential must use contraception or abstain during treatment and for specified times after last dose depending on treatment
- Blood pressure controlled at or below 150/90 mm Hg with stable medications within 1 week before randomization
- In Arm E, participants capable of producing sperm must refrain from sperm donation and use contraception or abstain from intercourse during and after treatment for specified durations
- Persons of childbearing potential in Arm E must use highly effective contraception or abstain during intervention and for required elimination period post-treatment
You will not qualify if you...
- Received systemic anticancer therapy including investigational agents within 4 weeks before starting study treatment
- Received radiotherapy within 2 weeks before starting study treatment
- Received lung radiation >30 Gray within 6 months before first dose
- Received live or live attenuated vaccine within 30 days before first dose
- Has another active malignancy requiring treatment or progressing within past 3 years
- Has active central nervous system metastases or carcinomatous meningitis unless meeting specific stability criteria
- History of severe hypersensitivity (grade 3 or higher) to study treatments or ingredients
- Active autoimmune disease requiring systemic treatment in past 2 years (except replacement therapies)
- Active infection requiring systemic therapy
- In Arms A-D: major surgery within 3 weeks before first dose, grade 3 or higher fistula, serious cardiovascular events within 12 months, active hemoptysis, gastrointestinal malabsorption, serious wounds or fractures, major hemorrhage or thromboembolic events recently, inflammatory bowel disease, recent gastrointestinal perforation, neurologic paraneoplastic syndrome, prior therapy with certain immune agents, prior anti-PD-1/L1 discontinuation due to adverse events, investigational agents or devices within 4 weeks, radiographic evidence of major blood vessel invasion or tumor cavitation, symptomatic fluid build-up, immunodeficiency or immunosuppressive therapy recently, known HIV infection, active hepatitis B or C, progression as initial response to first-line chemo with PD-1/L1 inhibitor, history of transplant, pneumonitis or interstitial lung disease
- In Arm E: prior treatment with CDH6-targeted or exatecan derivative ADC agents, investigational agents or devices within 4 weeks or 5 half-lives, chronic steroid treatment except certain exceptions, HIV infection with Kaposi's sarcoma or Castleman's disease, history or current interstitial lung disease or pneumonitis not ruled out at screening
AI-Screening
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Trial Site Locations
Total: 48 locations
1
Banner MD Anderson Cancer Center ( Site 0152)
Gilbert, Arizona, United States, 85234
Completed
2
Northside Hospital-Northside Hospital Oncology Network ( Site 0156)
Atlanta, Georgia, United States, 30342
Completed
3
Parkview Research Center at Parkview Regional Medical Center ( Site 0180)
Fort Wayne, Indiana, United States, 46845
Completed
4
Baptist Health Lexington-Research ( Site 0158)
Lexington, Kentucky, United States, 40503
Completed
5
University of Kentucky Chandler Medical Center-Medical Oncology ( Site 0157)
Lexington, Kentucky, United States, 40536
Completed
6
MFSMC-HJWCI-Oncology Research ( Site 0178)
Baltimore, Maryland, United States, 21237
Completed
7
Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0172)
Omaha, Nebraska, United States, 68130
Completed
8
Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0179)
Omaha, Nebraska, United States, 68130
Completed
9
Cleveland Clinic-Taussig Cancer Center ( Site 0166)
Cleveland, Ohio, United States, 44195
Completed
10
UPMC Hillman Cancer Center ( Site 0177)
Pittsburgh, Pennsylvania, United States, 15232
Completed
11
St Francis Cancer Center-Research Office ( Site 0167)
Greenville, South Carolina, United States, 29607
Completed
12
Virginia Cancer Institute ( Site 0169)
Richmond, Virginia, United States, 23229
Active, Not Recruiting
13
Westmead Hospital-Department of Medical Oncology ( Site 4004)
Westmead, New South Wales, Australia, 2145
Completed
14
The Prince Charles Hospital-Oncology Clinical Trials ( Site 4003)
Brisbane, Queensland, Australia, 4032
Completed
15
Monash Health-Oncology Research ( Site 4005)
Clayton, Victoria, Australia, 3168
Completed
16
Hollywood Private Hospital-Medical Oncology ( Site 4001)
Perth, Western Australia, Australia, 6009
Actively Recruiting
17
Standort Penzing der Klinik Ottakring-Abteilung für Atemwegs-und Lungenkrankheiten ( Site 3101)
Vienna, Austria, 1140
Actively Recruiting
18
Klinik Floridsdorf-Abteilung für Innere Medizin und Pneumologie ( Site 3100)
Vienna, Austria, 1210
Actively Recruiting
19
Cross Cancer Institute ( Site 3004)
Edmonton, Alberta, Canada, T6G 1Z2
Completed
20
Princess Margaret Cancer Centre ( Site 3003)
Toronto, Ontario, Canada, M5G 2M9
Completed
21
St. Marys Hospital Center ( Site 3000)
Montreal, Quebec, Canada, H3T 1M5
Completed
22
Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 3800)
Szolnok, Jász-Nagykun-Szolnok, Hungary, 5004
Completed
23
Rambam Health Care Campus-Oncology ( Site 3600)
Haifa, Israel, 3109601
Actively Recruiting
24
Shaare Zedek Medical Center-Oncology ( Site 3602)
Jerusalem, Israel, 9103102
Actively Recruiting
25
Meir Medical Center. ( Site 3601)
Kfar Saba, Israel, 4428164
Actively Recruiting
26
Rabin Medical Center-Oncology ( Site 3604)
Petah Tikva, Israel, 4941492
Actively Recruiting
27
Sheba Medical Center-ONCOLOGY ( Site 3603)
Ramat Gan, Israel, 5265601
Actively Recruiting
28
Humanitas-U.O di Oncologia medica ed Ematologia ( Site 3301)
Rozzano, Milano, Italy, 20089
Actively Recruiting
29
ospedale le scotte-U.O.C. Immunoterapia Oncologica ( Site 3300)
Siena, Tuscany, Italy, 53100
Active, Not Recruiting
30
Ospedale San Raffaele-Oncologia Medica ( Site 3303)
Milan, Italy, 20132
Completed
31
Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Toracica ( Site 3304)
Milan, Italy, 20141
Active, Not Recruiting
32
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier ( Site 3900)
Warsaw, Masovian Voivodeship, Poland, 02-781
Actively Recruiting
33
Warminsko-Mazurskie Centrum Chorob Płuc w Olsztynie ( Site 3903)
Olsztyn, Warmian-Masurian Voivodeship, Poland, 10-357
Completed
34
Krasnoyarsk Regional Oncology Dispensary, Named after Krizhanovsky ( Site 3708)
Krasnoyarsk, Krasnoyarsk Krai, Russia, 660133
Completed
35
Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 3702)
Saint Petersburg, Leningradskaya Oblast', Russia, 198255
Completed
36
GBUZ LOKB-Oncology department #1 ( Site 3701)
Saint Petersburg, Sankt-Peterburg, Russia, 194291
Completed
37
GBUZ "SPb CRPCstmc(o)" ( Site 3705)
Saint Petersburg, Sankt-Peterburg, Russia, 197758
Completed
38
N.N.Petrov Research Institute of Oncology-Department of Chemotherapy and Innovative Technologies ( Site 3703)
Saint Petersburg, Sankt-Peterburg, Russia, 197758
Completed
39
Scientific research institution of oncology named after N.N. Petrov-Thoracic oncology ( Site 3704)
Saint Petersburg, Russia, 197758
Completed
40
Seoul National University Bundang Hospital-Medical Oncology ( Site 4104)
Seongnam, Kyonggi-do, South Korea, 13620
Actively Recruiting
41
Chungbuk National University Hospital ( Site 4106)
Cheongju-si, North Chungcheong, South Korea, 28644
Actively Recruiting
42
Seoul National University Hospital ( Site 4101)
Seoul, South Korea, 03080
Completed
43
Asan Medical Center-Lung Cancer Center ( Site 4103)
Seoul, South Korea, 05505
Completed
44
Samsung Medical Center ( Site 4100)
Seoul, South Korea, 06351
Actively Recruiting
45
Instituto Catalan de Oncologia - Hospital Duran i Reynals ( Site 3403)
L'Hospitalet de Llobregat, Catalonia, Spain, 08908
Actively Recruiting
46
Hospital Universitari Vall d'Hebron-Oncology ( Site 3401)
Barcelona, Spain, 08035
Actively Recruiting
47
Hospital Clinic de Barcelona ( Site 3404)
Barcelona, Spain, 08036
Actively Recruiting
48
Cantonal Hospital St.Gallen-Oncology & Hematology ( Site 3502)
Sankt Gallen, Canton of St. Gallen, Switzerland, 9000
Active, Not Recruiting
Research Team
T
Toll Free Number
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
5
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