A Study of Pembrolizumab Plus Epacadostat With Platinum-based Chemotherapy Versus Pembrolizumab Plus Platinum-based Chemotherapy Plus Placebo in Metastatic Non-Small Cell Lung Cancer (KEYNOTE-715-06/ECHO-306-06)

Lung Cancer Clinical Trial

Official title:

A Randomized Phase 2 Study of the Combination of Pembrolizumab (MK-3475) Plus Epacadostat (INCB024360) With Platinum-based Chemotherapy Versus Pembrolizumab Plus Platinum-based Chemotherapy Plus Placebo as First-Line Treatment in Patients With Metastatic Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03322566
• Other study ID #: KEYNOTE-715-06/ECHO-306-06
• Secondary ID: 2017-001810-27
• Status: Completed
• Phase: Phase 2
• Start date: January 9, 2018
• Est. completion date: October 16, 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 was to evaluate the efficacy and safety of pembrolizumab plus epacadostat with platinum-based chemotherapy versus pembrolizumab plus platinum-based chemotherapy plus placebo as first-line therapy in participants with metastatic non-small cell lung cancer (NSCLC).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 233
• Est. completion date: October 16, 2020
• Est. primary completion date: December 13, 2018
• 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

• 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.

• Provide tumor tissue sample.

Exclusion Criteria:

• Known untreated central nervous system metastases and/or carcinomatous meningitis

• History of (non-infectious) 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.
• Platinum-based chemotherapy
Investigator selected one of the following regimens: pemetrexed + cisplatin, pemetrexed + carboplatin, or paclitaxel + carboplatin, depending on histology.
• Placebo
Matching placebo administered orally twice daily.

Locations

Country	Name	City	State
Australia	Blacktown Hospital	Blacktown	New South Wales
Australia	Cairns Base Hospital	Cairns	Queensland
Australia	Chris OBrien Lifehouse	Camperdown	New South Wales
Australia	MNCCI Port Macquarie Base Hospital	Port Macquarie	New South Wales (Australia)
Australia	The Crown Princess Mary Cancer Centre Westmead	Westmead	New South Wales
Australia	Southern Medical Day Care Centre	Wollongong	New South Wales
Canada	CISSS de la Monteregie-Centre	Greenfield Park	Quebec
Canada	BCCA-Cancer Centre of the Southern Interior	Kelowna	British Columbia
Canada	CSSS de Laval- Hopital de la Cite de la Sante	Laval	Quebec
Canada	CIUSSS du Nord-de-l'ILe-de-Montreal Hopital du Sacre-Coeur de Montreal	Montréal	Quebec
Canada	CIUSSS Ouest de l'Ile - St-Mary's Hospital	Montréal	Quebec
Canada	Lions Gate Hospital	North Vancouver	British Columbia
Canada	CHU de Quebec - Hotel-Dieu de Quebec	Quebec
Canada	CIUSSS de la Mauricie-et-du-Centre-du-Quebec	Trois-Rivières	Quebec
Hungary	Orszagos Koranyi TBC es Pulmonologiai Intezet	Budapest
Hungary	Veszprem Megyei Tudogyogyintezet	Farkasgyepu
Hungary	Bekes Megyei Pandy Kalman Korhaz	Gyula
Hungary	CRU Hungary Kft.	Miskolc
Hungary	Zala Megyei Korhaz Pozvai Telephely	Pozva	Zalaegerszeg
Hungary	Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet	Szolnok
Ireland	St Vincents University Hospital	Dublin
Israel	Ha Emek Medical Center	Afula
Israel	Soroka Medical Center	Be'er Sheva
Israel	Rambam Medical Center	Haifa
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center	Petah Tikva
Israel	Chaim Sheba Medcal Center	Ramat Gan
Italy	Centro Di Riferimento Oncologico	Aviano
Italy	A.O.U. Policlinico Vittorio Emanuele - Presidio Gaspare Rodolico	Catania
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Istituto Europeo di Oncologia	Milano
Italy	Ospedale San Gerardo - ASST Monza	Monza
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Mexico	Medical Care Research S.A. de C.V.	Mérida	Yucatan
Mexico	Oaxaca Site Management Organization S.C.	Oaxaca
Mexico	FAICIC Clinical Research	Veracruz
Russian Federation	Belgorod Regional Oncology Dispensary	Belgorod
Russian Federation	Udmurtia Republic Regional Clinical Oncology Dispensary	Izhevsk
Russian Federation	Republican Clinical Oncology Dispensary of Tatarstan MoH	Kazan
Russian Federation	Central Clinical Hospital with polyclinic	Moscow
Russian Federation	Moscow Research Oncology Institute	Moscow
Russian Federation	SBI of Stavropol region Pyatigorskiy Oncologic dispensary	Pyatigorsk
Russian Federation	SBHI Leningrad Regional Clinical Hospital	Saint Petersburg
Russian Federation	SBHI Samara Regional Clinical Oncology Dispensary	Samara
Russian Federation	Oncological Dispensary #2 of Ministry of Health of Krasnodar region	Sochi
Russian Federation	Tomsk Scientific Research Institute of Oncology	Tomsk
Spain	Hospital Juan Ramón Jimenez	Huelva
Spain	Institut Catala Oncologia de Bellvitge - ICO	L'Hospitalet De Llobregat
Spain	Hospital Universitario Insular de Gran Canaria	Las Palmas De Gran Canaria	Gran Canaria
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario La Fe	Valencia
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
Taiwan	Chang Gung Medical Foundation, Kaohsiung Branch	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Medical Foundation, Linkou Branch	Taoyuan
Turkey	Baskent Universitesi Adana Uygulama ve Arastirma Hastanesi	Adana
Turkey	Cukurova Universitesi Tip Fakultesi Balcali Hastanesi	Adana
Turkey	Hacettepe Universitesi Tip Fakultesi Hastanesi	Ankara
Turkey	Uludag Universitesi Tip Fakultesi	Bursa
Turkey	Pamukkale Unv. Tip Fak	Denizli
Turkey	Istanbul Universitesi Cerrahpasa Tip Fakultesi	Istanbul
Turkey	Ege Universitesi Tip Fakultesi Hastanesi	Izmir	Bornova
Turkey	Samsun Medical Park Hastanesi	Samsun
Turkey	Namik Kemal University Medical Faculty	Tekirdag
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	North Middlesex Hospital	London
United Kingdom	Freeman Hospital Newcastle upon Tyne Foundation NHS Trust	Newcastle Upon Tyne
United Kingdom	Mount Vernon Cancer Centre	Northwood	Middlesex
United States	New York Oncology Hematology P.C	Albany	New York
United States	University of Michigan	Ann Arbor	Michigan
United States	St. Vincent Healthcare Frontier Cancer Center	Billings	Montana
United States	Oncology & Hematology Assoc. SW Virginia, Inc., DBA Blue Ridge Cancer Care	Blacksburg	Virginia
United States	Lynn Cancer Institute	Boca Raton	Florida
United States	Emily Couric Clinical Cancer Center	Charlottesville	Virginia
United States	Tennessee Oncology, PLLC/The Sarah Cannon Research Institute	Chattanooga	Tennessee
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	Southern Cancer Center, PC	Daphne	Alabama
United States	Texas Oncology-Denton South	Denton	Texas
United States	St. Luke's Hospital - Anderson Campus	Easton	Pennsylvania
United States	Florida Cancer Specialists (South Region)	Fort Myers	Florida
United States	PPG-Oncology	Fort Wayne	Indiana
United States	Western Regional Medical Center, Inc.	Goodyear	Arizona
United States	Tennessee Oncology, PLLC/The Sarah Cannon Research Institute	Nashville	Tennessee
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	MMCORC	Saint Louis Park	Minnesota
United States	Florida Cancer Specialists (North Region)	Saint Petersburg	Florida
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Arizona Oncology Associates PC- HOPE	Tucson	Arizona
United States	Southwestern Regional Medical Center, Inc.	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Incyte Corporation	Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Hungary,  Ireland,  Israel,  Italy,  Korea, Republic of,  Mexico,  Russian Federation,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo	ORR is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) based on blinded independent central review (BICR).	Assessed every 12 weeks up to 24 months
Secondary	Progression-free Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo	Defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurs first.	Up to 24 months
Secondary	Overall Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo	Defined as the time from randomization to death due to any cause.	Up to 24 months
Secondary	Duration of Response of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo	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 24 months
Secondary	Safety and Tolerability of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo as Measured by the Number of Participants Experiencing Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to 25 months
Secondary	Safety and Tolerability of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo as Measured by the Number of Participants Discontinuing Study Drug Due to AEs	An AE is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of any study drug, whether or not considered related to the study drug.	Up to 25 months