Pembrolizumab Plus Epacadostat vs Pembrolizumab Plus Placebo in Metastatic Non-Small Cell Lung Cancer (KEYNOTE-654-05/ECHO-305-05)

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03322540
• Other study ID #: KEYNOTE-654-05/ECHO-305-05
• Status: Completed
• Phase: Phase 2
• Start date: December 15, 2017
• Est. completion date: November 9, 2020

Study information

• Verified date: January 2022
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: November 9, 2020
• Est. primary completion date: January 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• Pembrolizumab
Pembrolizumab administered intravenously every 3 weeks.
• Epacadostat
Epacadostat administered orally twice daily.
• Placebo
Matching placebo administered orally twice daily.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Incyte Corporation	Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Denmark,  Estonia,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Poland,  Russian Federation,  Spain,  Switzerland,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) of Pembrolizumab Plus Epacadostat Versus Pembrolizumab Plus Placebo	ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 based on blinded independent central review (BICR).	Up to approximately 6 months
Secondary	Progression-free Survival (PFS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo	PFS is defined as the time from randomization to the first documented progressive disease per RECIST v1.1 based on BICR or death due to any cause, whichever occurs first.	Up to approximately 36 months
Secondary	Overall Survival (OS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo	OS is defined as the time from randomization to death due to any cause.	Up to approximately 36 months
Secondary	Duration of Response (DOR) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo	DOR is defined as the time from the earliest date of qualifying response until earliest date of disease progression per RECIST v1.1 or death from any cause, whichever comes first.	Up to approximately 36 months
Secondary	Number of Participants With Adverse Events (AEs)	AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to 37 months
Secondary	Number of Participants Who Discontinued Study Drug Due to AEs	AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to 37 months