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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04938817




Registration number
NCT04938817
Ethics application status
Date submitted
21/06/2021
Date registered
24/06/2021
Date last updated
5/04/2024

Titles & IDs
Public title
Safety and Efficacy Study of Pembrolizumab (MK-3475) in Combination With Investigational Agents for the Treatment of Extensive-Stage Small Cell Lung Cancer (ES-SCLC) in Need of Second-Line Therapy (MK-3475-B98/KEYNOTE-B98)
Scientific title
A Phase 1b/2 Study to Evaluate the Efficacy and Safety of Pembrolizumab in Combination With Investigational Agents for the Treatment of Participants With PD-1/L1-refractory Extensive-Stage Small Cell Lung Cancer in Need of Second-Line Therapy (KEYNOTE-B98)
Secondary ID [1] 0 0
MK-3475-B98
Secondary ID [2] 0 0
3475-B98
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Small Cell Lung Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - coformulation pembrolizumab/quavonlimab
Treatment: Drugs - lenvatinib
Other interventions - MK-4830
Other interventions - coformulation favezelimab/pembrolizumab

Experimental: Coformulation Pembrolizumab/Quavonlimab - 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.

Experimental: Coformulation Pembrolizumab/Quavonlimab + Lenvatinib - 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.

Experimental: Coformulation Pembrolizumab/Quavonlimab + MK-4830 - 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.

Experimental: Coformulation Favezelimab/Pembrolizumab - 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.


Other interventions: coformulation pembrolizumab/quavonlimab
Intravenous (IV) infusion

Treatment: Drugs: lenvatinib
Oral administration

Other interventions: MK-4830
IV infusion

Other interventions: coformulation favezelimab/pembrolizumab
IV infusion
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Up to 21 days in Cycle 1 (Cycle 1 = 21 days)
Primary outcome [2] 0 0
Number of Participants Who Experience at Least One Adverse Event (AE)
Timepoint [2] 0 0
Up to approximately 60 months
Primary outcome [3] 0 0
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Timepoint [3] 0 0
Up to approximately 60 months
Primary outcome [4] 0 0
Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [4] 0 0
Up to approximately 60 months
Secondary outcome [1] 0 0
Progression-free Survival (PFS) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [1] 0 0
Up to approximately 60 months
Secondary outcome [2] 0 0
Duration of Response (DOR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [2] 0 0
Up to approximately 60 months

Eligibility
Key inclusion criteria
- 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)

- 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 woman of
childbearing potential (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

- A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as
required by local regulations) within 24 hours 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 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

- Has a predicted life expectancy of >3 months
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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 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 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 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

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
2/11/2026
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Westmead Hospital-Department of Medical Oncology ( Site 4004) - Westmead
Recruitment hospital [2] 0 0
The Prince Charles Hospital-Oncology Clinical Trials ( Site 4003) - Brisbane
Recruitment hospital [3] 0 0
Monash Health-Oncology Research ( Site 4005) - Clayton
Recruitment hospital [4] 0 0
Hollywood Private Hospital-Medical Oncology ( Site 4001) - Perth
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4032 - Brisbane
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Nebraska
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
South Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
Austria
State/province [11] 0 0
Wien
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
Hungary
State/province [15] 0 0
Jasz-Nagykun-Szolnok
Country [16] 0 0
Israel
State/province [16] 0 0
Haifa
Country [17] 0 0
Israel
State/province [17] 0 0
Jerusalem
Country [18] 0 0
Israel
State/province [18] 0 0
Kfar Saba
Country [19] 0 0
Israel
State/province [19] 0 0
Petah Tikva
Country [20] 0 0
Israel
State/province [20] 0 0
Ramat Gan
Country [21] 0 0
Italy
State/province [21] 0 0
Lombardia
Country [22] 0 0
Italy
State/province [22] 0 0
Milano
Country [23] 0 0
Italy
State/province [23] 0 0
Toscana
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Chungbuk
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Kyonggi-do
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Seoul
Country [27] 0 0
Poland
State/province [27] 0 0
Mazowieckie
Country [28] 0 0
Poland
State/province [28] 0 0
Warminsko-mazurskie
Country [29] 0 0
Russian Federation
State/province [29] 0 0
Krasnoyarskiy Kray
Country [30] 0 0
Russian Federation
State/province [30] 0 0
Leningradskaya Oblast
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Sankt-Peterburg
Country [32] 0 0
Spain
State/province [32] 0 0
Cataluna
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Switzerland
State/province [34] 0 0
Sankt Gallen

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is a rolling arm study of pembrolizumab in combination with investigational agents
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04938817
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries