Clinical trial NCT04924101: 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)
Official title: A Phase 2 Study to Evaluate the Efficacy and Safety of Pembrolizumab Plus Investigational Agents in Combination With Etoposide and Cisplatin or Carboplatin for the First-Line Treatment of Participants With Extensive-Stage Small Cell Lung Cancer (KEYNOTE-B99)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
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)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-06-11
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Is expected to require any other form of antineoplastic therapy for SCLC, including radiation therapy, while on study
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
* Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation. A participant that meets this exclusion criterion but is otherwise deemed eligible for the study may be randomized across the specific intervention groups.
* Has symptomatic ascites, pleural effusion, or pericardial effusion. A participant who is clinically stable following treatment for these conditions is eligible
* 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 intervention
* 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: a) Completed treatment at least 14 days before the first dose of study intervention b) Have no evidence of new or enlarging brain metastases confirmed by posttreatment repeat brain imaging performed at least 4 weeks after pretreatment brain imaging, and c) Are neurologically stable without the need for steroids for at least 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 mm or less in size and 3 or fewer in number
* Has a history of severe hypersensitivity reaction to any study intervention and/or any of its excipients
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has a known history of, or active, neurologic paraneoplastic syndrome
* Has an active infection requiring systemic therapy
* Has a known history of human immunodeficiency virus (HIV) infection and/or Hepatitis B virus infection or an active Hepatitis C infection
* Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
* Has had an allogenic tissue/solid organ transplant

Primary outcomes:
measure: 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)
timeFrame: Up to approximately 5 years
measure: Six-Month Progression-Free Survival (PFS) as Assessed by BICR per RECIST 1.1
timeFrame: Up to approximately 6 months
Secondary outcomes:
measure: Duration of Response (DOR) as Assessed by BICR per RECIST 1.1
timeFrame: Up to approximately 5 years
measure: Progression-Free Survival (PFS) as Assessed by BICR per RECIST 1.1
timeFrame: Up to approximately 5 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 5 years
measure: Percent Change From Baseline in Tumor Size as Assessed by BICR
timeFrame: Baseline, 5 years
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 5 years
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 5 years
measure: Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) Global Health Status/Quality of Life Scale (Items 29 and 30) at Week 19
timeFrame: Baseline, Week 19
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center ( Site 0102)
state: Arizona
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus ( Site 0104)
state: Colorado
city: Atlanta
country: United States
facility: Georgia Cancer Specialists ( Site 0106)
state: Georgia
city: Fort Wayne
country: United States
facility: Parkview Research Center at Parkview Regional Medical Center ( Site 0130)
state: Indiana
city: Lexington
country: United States
facility: Baptist Health Lexington-Research ( Site 0108)
state: Kentucky
city: Baltimore
country: United States
facility: MFSMC-HJWCI-Oncology Research ( Site 0128)
state: Maryland
city: Omaha
country: United States
facility: Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0122)
state: Nebraska
city: Omaha
country: United States
facility: Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0129)
state: Nebraska
city: Mineola
country: United States
facility: Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 0114)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center ( Site 0115)
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic-Taussig Cancer Center ( Site 0116)
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center ( Site 0127)
state: Pennsylvania
city: Greenville
country: United States
facility: St Francis Cancer Center-Research Office ( Site 0117)
state: South Carolina
city: Richmond
country: United States
facility: Virginia Cancer Institute ( Site 0119)
state: Virginia
city: Vienna
country: Austria
facility: Klinik Penzing-2. Lungenabteilung ( Site 2101)
state: Wien
city: Wien
country: Austria
facility: Klinik Floridsdorf-Abteilung für Innere Medizin und Pneumologie ( Site 2100)
city: Hamilton
country: Canada
facility: Hamilton Health Sciences-Juravinski Cancer Centre ( Site 2003)
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre-Kingston General Hospital Site ( Site 2005)
state: Ontario
city: Montreal
country: Canada
facility: St. Marys Hospital Center ( Site 2000)
state: Quebec
city: Szolnok
country: Hungary
facility: Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 2800)
state: Jasz-Nagykun-Szolnok
city: Budapest
country: Hungary
facility: Országos Korányi Pulmonológiai Intézet-XIV. Tüdöbelgyógyászat ( Site 2806)
state: Pest
city: Törökbálint
country: Hungary
facility: Torokbalint Tudogyogyintezet-Onkopulmonologiai Jarobeteg Centrum ( Site 2801)
state: Pest
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Szent Rafael Kórház-Pulmonológia ( Site 2805)
state: Zala
city: Budapest
country: Hungary
facility: Semmelweis University-Pulmonológiai Klinika ( Site 2802)
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology ( Site 2600)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center ( Site 2602)
city: Kfar Saba
country: Israel
facility: Meir Medical Center ( Site 2601)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center-Oncology ( Site 2604)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center-ONCOLOGY ( Site 2603)
city: Milano
country: Italy
facility: Ospedale San Raffaele-Oncologia Medica ( Site 2303)
state: Lombardia
city: Siena
country: Italy
facility: ospedale le scotte-U.O.C. Immunoterapia Oncologica ( Site 2300)
state: Toscana
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Toracica ( Site 2304)
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital ( Site 1107)
state: Chungbuk
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital ( Site 1104)
state: Kyonggi-do
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University Of Korea St. Vincent's Hospital ( Site 1106)
state: Kyonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 1101)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1105)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center-Department of Oncology ( Site 1103)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 1100)
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier
state: Mazowieckie
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zespó Grulicy i Chorób Puc w Olsztynie-Oddzial Onkologii z Pododdzialem Chemi
state: Warminsko-mazurskie
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Oncology Dispensary, Named after Krizhanovsky ( Site 2708)
state: Krasnoyarskiy Kray
city: Saint Petersburg
country: Russian Federation
facility: N.N.Petrov Research Institute of Oncology-Department of Chemotherapy and Innovative Technologies ( S
state: Sankt-Peterburg
city: Saint-Petersburg
country: Russian Federation
facility: GBUZ "SPb CRPCstmc(o)" ( Site 2705)
state: Sankt-Peterburg
city: Sankt-Peterburg
country: Russian Federation
facility: Scientific research institution of oncology named after N.N. Petrov-Thoracic oncology ( Site 2704)
city: L'Hospitalet de Llobregat
country: Spain
facility: Instituto Catalan de Oncologia - Hospital Duran i Reynals ( Site 2403)
state: Cataluna
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Insular de Gran Canaria ( Site 2402)
state: Las Palmas
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron-Oncology ( Site 2401)
city: st.Gallen
country: Switzerland
facility: Cantonal Hospital St.Gallen-Oncology & Hematology ( Site 2502)
state: Sankt Gallen
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: