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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

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)

A Phase 1b/2 Study to Evaluate the Efficacy and Safety of Investigational Agents as Monotherapy or in Combination With Pembrolizumab for the Treatment of Participants With PD-1/L1-refractory Extensive-Stage Small Cell Lung Cancer in Need of Second-Line Therapy (KEYNOTE-B98)

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) is a Phase 1 / Phase 2 interventional studying Small Cell Lung Carcinoma, sponsored by Merck Sharp & Dohme LLC. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Small Cell Lung Carcinoma, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 110 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Small Cell Lung Carcinoma subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: The main inclusion criteria include but are not limited to the following: - Arms A-E: - Has diagnosed by tissue sample (biopsy-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 tumors that can be measured on scans 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * 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 * Female participants must abstain from breastfeeding during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, MK-4830, or favezelimab/pembrolizumab or 7 days after the last dose of lenvatinib, whichever occurs last * Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 millimeters of mercury (mm Hg) with no change in antihypertensive medications within 1 week before allocation/randomization * Arm E: * If capable of producing sperm, the participant agrees to refrain from donating sperm and abstain from penile-vaginal intercourse or use a penile/external condom when having penile-vaginal intercourse with a nonparticipant of childbearing potential who is not currently pregnant. The length of time required to continue contraception for the study intervention R-Dx-d is 120 days * If a person of childbearing potential (POCBP) must use a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or if they adhere to penile-vaginal intercourse abstinence 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 the study intervention after the last dose of study intervention. In addition, the participant agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during this period for the purpose of reproduction. The length of time required to continue contraception for the study intervention R-Dx-d is 210 days Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * 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 * Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks before the first dose of study treatment * 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 the start of study treatment * Has any major hemorrhage or venous thromboembolic events within 3 months before the start of study treatment * Has a history of inflammatory bowel disease * Has a history of a gastrointestinal perforation within 6 months before the start of study treatment * Has a known history of, or active, neurologic paraneoplastic syndrome * Has received prior therapy with a receptor tyrosine kinase (RTK) inhibitor or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), anti-immunoglobulin-like transcript (ILT)-4, or anti-lymphocyte-activation gene 3 (LAG-3) agents * Has received prior therapy with an anti-PD-1/L1 agent and was permanently discontinued from that treatment due to a treatment-related adverse event * Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration * Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation * Has symptomatic ascites, pleural effusion, or pericardial effusion * 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 treatment * Has a known history of Human Immunodeficiency Virus (HIV) infection * Has concurrent active HBV or HCV * Has progressive disease as initial response to first-line systemic chemotherapy in combination with PD-1/L1 inhibitor for ES-SCLC * Has had an allogenic tissue/solid organ transplant * Arm E: * Received prior treatment with a CDH6-targeted agent or an ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan, datopotamab deruxtecan) * Has received an investigational agent or has used an investigational device within 4 weeks (or 5 half-lives, whichever is shorter) prior to study intervention administration * Has Chronic steroid treatment (\>10 mg/day prednisone \[or equivalent\] per day), except for inhaled steroids for asthma or COPD, mineralocorticoids (e.g., fludrocortisone) for participants with orthostatic hypotension, topical steroids for mild skin conditions, low-dose supplemental corticosteroids for adrenocortical insufficiency, Premedication for treatment groups and/or premedication in case of any hypersensitivity, or intra-articular steroid injections * Is an HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease

Treatments Being Tested

BIOLOGICAL

coformulation pembrolizumab/quavonlimab

Intravenous (IV) infusion

DRUG

lenvatinib

Oral administration

BIOLOGICAL

MK-4830

IV infusion

BIOLOGICAL

coformulation favezelimab/pembrolizumab

IV infusion

BIOLOGICAL

R-DXd

IV Infusion

Locations (20)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Banner MD Anderson Cancer Center ( Site 0152)
Gilbert, Arizona, United States
Northside Hospital-Northside Hospital Oncology Network ( Site 0156)
Atlanta, Georgia, United States
Parkview Research Center at Parkview Regional Medical Center ( Site 0180)
Fort Wayne, Indiana, United States
Baptist Health Lexington-Research ( Site 0158)
Lexington, Kentucky, United States
University of Kentucky Chandler Medical Center-Medical Oncology ( Site 0157)
Lexington, Kentucky, United States
MFSMC-HJWCI-Oncology Research ( Site 0178)
Baltimore, Maryland, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0172)
Omaha, Nebraska, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0179)
Omaha, Nebraska, United States
Cleveland Clinic-Taussig Cancer Center ( Site 0166)
Cleveland, Ohio, United States
UPMC Hillman Cancer Center ( Site 0177)
Pittsburgh, Pennsylvania, United States
St Francis Cancer Center-Research Office ( Site 0167)
Greenville, South Carolina, United States
Virginia Cancer Institute ( Site 0169)
Richmond, Virginia, United States
Westmead Hospital-Department of Medical Oncology ( Site 4004)
Westmead, New South Wales, Australia
The Prince Charles Hospital-Oncology Clinical Trials ( Site 4003)
Brisbane, Queensland, Australia
Monash Health-Oncology Research ( Site 4005)
Clayton, Victoria, Australia
Hollywood Private Hospital-Medical Oncology ( Site 4001)
Perth, Western Australia, Australia
Standort Penzing der Klinik Ottakring-Abteilung für Atemwegs-und Lungenkrankheiten ( Site 3101)
Vienna, Austria
Klinik Floridsdorf-Abteilung für Innere Medizin und Pneumologie ( Site 3100)
Vienna, Austria
Cross Cancer Institute ( Site 3004)
Edmonton, Alberta, Canada
Princess Margaret Cancer Centre ( Site 3003)
Toronto, Ontario, Canada

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04938817), the sponsor (Merck Sharp & Dohme LLC), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04938817 clinical trial studying?

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 … The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT04938817?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04938817?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04938817. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04938817. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.