Clinical trial NCT03322540: Pembrolizumab Plus Epacadostat vs Pembrolizumab Plus Placebo in Metastatic Non-Small Cell Lung Cancer (KEYNOTE-654-05/ECHO-305-05)
Official title: A Phase 2, Randomized, Double-Blind Study of Pembrolizumab (MK-3475) Plus Epacadostat (INCB024360) Versus Pembrolizumab Plus Placebo as First-Line Treatment in Patients With Metastatic Non-Small Cell Lung Cancer Expressing High Levels of PD-L1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: non-small cell lung cancer
programmed cell death 1 (PD-1) inhibitor
indoleamine 2
3-dioxygenase 1 (IDO1) inhibitor
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-10-26
Enrollment: 154
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 efficacy and safety of pembrolizumab plus epacadostat compared to pembrolizumab plus placebo as first-line treatment in participants with metastatic non-small cell lung cancer (NSCLC) expressing high levels of programmed cell death ligand 1 (PD-L1).


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of stage IV NSCLC without epidermal growth factor receptor (EGFR)-sensitizing mutation, ROS1 and/or anaplastic lymphoma kinase (ALK) translocation.
* Measurable disease based on RECIST 1.1.
* Tumor tissue that demonstrates programmed cell death ligand 1 (PD-L1) expression in ≥ 50% of tumor cells (tumor proportion score \[TPS\] ≥ 50%) as assessed by immunohistochemistry at a central laboratory.
* Life expectancy of at least 3 months.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate organ function per protocol-defined criteria.

Exclusion Criteria:

* Known untreated central nervous system metastases and/or carcinomatous meningitis.
* History of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
* Symptomatic ascites or pleural effusion.
* Known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
* Active autoimmune disease that has required systemic treatment in past 2 years.
* Has had an allogeneic tissue/solid organ transplant.
* Has a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority.
* Has known history of or is positive for active Hepatitis B (HBsAg reactive) or has active Hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.
* History or presence of an abnormal electrocardiogram (ECG) that, in the Investigator's opinion, is clinically meaningful.
* Use of protocol-defined prior/concomitant therapy.

Primary outcomes:
measure: Objective Response Rate (ORR) of Pembrolizumab Plus Epacadostat Versus Pembrolizumab Plus Placebo
timeFrame: Up to approximately 6 months
Secondary outcomes:
measure: Progression-free Survival (PFS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo
timeFrame: Up to approximately 36 months
measure: Overall Survival (OS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo
timeFrame: Up to approximately 36 months
measure: Duration of Response (DOR) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo
timeFrame: Up to approximately 36 months
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 37 months
measure: Number of Participants Who Discontinued Study Drug Due to AEs
timeFrame: Up to 37 months
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center, Inc.
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists (South Region)
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists (North Region)
state: Florida
city: Newnan
country: United States
facility: Southeastern Regional Medical Center, Inc.
state: Georgia
city: Annapolis
country: United States
facility: Anne Arundel Health System Research Institute
state: Maryland
city: Baltimore
country: United States
facility: Weinberg Cancer Institute at Franklin Square
state: Maryland
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Coon Rapids
country: United States
facility: Minnesota Oncology Hematology, PA
state: Minnesota
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Chattanooga
country: United States
facility: Tennessee Oncology, PLLC/The Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC/The Sarah Cannon Research Institute
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology-South Austin
state: Texas
city: Heidelberg
country: Australia
facility: Austin Health-Austin Hospital
state: Victoria
city: Murdoch
country: Australia
facility: St John of God Murdoch Medical Clinic
state: Western Australia
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Moncton
country: Canada
facility: Moncton Hospital - Horizon Health Network
state: New Brunswick
city: Brampton
country: Canada
facility: William Osler Health System
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: Sault Ste Marie
country: Canada
facility: Sault Area Hospital
state: Ontario
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Herning
country: Denmark
facility: Regionshospitalet Herning
city: Odense
country: Denmark
facility: Odense Universitetshospital
city: Tartu
country: Estonia
facility: SA Tartu Ulikooli Kliinikum
city: Galway
country: Ireland
facility: Galway University Hospital
state: Connacht
city: Dublin
country: Ireland
facility: St Vincents University Hospital
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Genova
country: Italy
facility: IRCCS A.O.U. San Martino - IST
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center
state: Aichi
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
state: Ishikawa
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Sendai
country: Japan
facility: Sendai Kousei Hospital
state: Miyagi
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital
state: Osaka
city: Osakasayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Nagaizumi-chō
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka Prefecture
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: Nippon Medical School Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital
city: Cheongju si
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungcheongbuk Do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Gacheon University Gil Medical Center
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
state: Pahang
city: Putrajaya
country: Malaysia
facility: Institut Kanser Negara - National Cancer Institute
state: Wilayah Persekutuan
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Kuala Lumpur
country: Malaysia
facility: Pantai Hospital Kuala Lumpur
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii SPZOZ
state: Swietokrzyskie
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka Lukaszczyka
city: Gliwice
country: Poland
facility: Centrum Onkologii. Instytut im. Marii Sklodowskiej-Curie
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii SPZOZ
city: Konin
country: Poland
facility: Przychodnia Lekarska Komed
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc
city: Tarnobrzeg
country: Poland
facility: Wojewodzki Szpital im. Zofii z Zamoyskich Tarnowskiej w Tarnobrzegu
city: Warszawa
country: Poland
facility: Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie
city: Belgorod
country: Russian Federation
facility: Belgorod Regional Oncology Dispensary
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital with polyclinic
city: Moscow
country: Russian Federation
facility: Moscow Research Oncology Institute named after P.A. Hertsen
city: Saint Petersburg
country: Russian Federation
facility: SBHI Leningrad Regional Clinical Hospital
city: Samara
country: Russian Federation
facility: SBHI Samara Regional Clinical Oncology Dispensary
city: Ufa
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Republic of Bashkortostan
city: Vigo
country: Spain
facility: Hospital Alvaro Cunqueiro
state: Pontevedra
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Clinico de Valencia
city: Bellinzona
country: Switzerland
facility: Oncological Institute of Southern Switzerland
city: Bern
country: Switzerland
facility: Inselspital Universitatsspital Bern
city: Geneva
country: Switzerland
facility: Hopitaux Universitaires de Geneve HUG.
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zuerich
country: Switzerland
facility: Universitaetsspital Zuerich
city: Adana
country: Turkey
facility: Basken Uni. Adana Dr.Turgut Noyan Uygulama ve Arastirma Merkezi
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty
city: Antalya
country: Turkey
facility: Akdeniz Universitesi Tip Fakultesi
city: Kayseri
country: Turkey
facility: Erciyes Universitesi Tip Fakultesi
city: Konya
country: Turkey
facility: Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi
city: Kryvyi Rih
country: Ukraine
facility: MI Kryviy Rih Center of Dnipropetrovsk Regional Council
state: Dnipropetrovsk Region
city: Dnipropetrovsk
country: Ukraine
facility: Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC
city: Kharkiv
country: Ukraine
facility: Grigoriev Institute for medical Radiology NAMS of Ukraine
city: Kirovohrad
country: Ukraine
facility: PP PPC Acinus Medical and Diagnostic Centre
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Oncological Center
city: Kyiv
country: Ukraine
facility: Dobryi Prognoz
city: Lutsk
country: Ukraine
facility: Volyn Regional Oncological Dispensary
city: Odesa
country: Ukraine
facility: MI Odessa Regional Oncological Centre
city: Zaporizhzhya
country: Ukraine
facility: Zaporizhzhya Regional Clinical Oncology Center
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospital NHS Trust. St. James University Hospital
Study officials:
affiliation: Incyte Corporation
name: Lance Leopold, MD
role: STUDY_DIRECTOR
References: