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)
- Conditions
- Lung Cancer
- Interventions
- Registration Number
- NCT03322566
- Lead Sponsor
- Incyte Corporation
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 233
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab + Chemotherapy + Epacadostat Epacadostat Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m\^2 IV infusion, Q3W + cisplatin 75 mg/m\^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m\^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). Pembrolizumab + Epacadostat Epacadostat Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, BID in each 21 day cycle for up to 35 cycles. Pembrolizumab + Chemotherapy + Epacadostat Platinum-based chemotherapy Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m\^2 IV infusion, Q3W + cisplatin 75 mg/m\^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m\^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). Pembrolizumab + Chemotherapy + Placebo Platinum-based chemotherapy Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m\^2 IV infusion, Q3W + cisplatin 75 mg/m\^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m\^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). Pembrolizumab + Chemotherapy + Placebo Placebo Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m\^2 IV infusion, Q3W + cisplatin 75 mg/m\^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m\^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m\^2 IV infusion, Q3W + cisplatin 75 mg/m\^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m\^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). Pembrolizumab + Chemotherapy + Placebo Pembrolizumab Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m\^2 IV infusion, Q3W + cisplatin 75 mg/m\^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m\^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). Pembrolizumab + Epacadostat Pembrolizumab Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, BID in each 21 day cycle for up to 35 cycles.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo Assessed every 12 weeks up to 24 months 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).
- Secondary Outcome Measures
Name Time Method Safety and Tolerability of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo as Measured by the Number of Participants Experiencing Adverse Events (AEs) Up to 25 months 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.
Progression-free Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo Up to 24 months 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.
Overall Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo Up to 24 months Defined as the time from randomization to death due to any cause.
Duration of Response of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo Up to 24 months 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.
Safety and Tolerability of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo as Measured by the Number of Participants Discontinuing Study Drug Due to AEs Up to 25 months 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.
Trial Locations
- Locations (93)
Chris OBrien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
St. Vincent Healthcare Frontier Cancer Center
🇺🇸Billings, Montana, United States
Orszagos Koranyi TBC es Pulmonologiai Intezet
ðŸ‡ðŸ‡ºBudapest, Hungary
SBHI Samara Regional Clinical Oncology Dispensary
🇷🇺Samara, Russian Federation
Oncological Dispensary #2 of Ministry of Health of Krasnodar region
🇷🇺Sochi, Russian Federation
BCCA-Cancer Centre of the Southern Interior
🇨🇦Kelowna, British Columbia, Canada
Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet
ðŸ‡ðŸ‡ºSzolnok, Hungary
St Vincents University Hospital
🇮🇪Dublin, Ireland
Belgorod Regional Oncology Dispensary
🇷🇺Belgorod, Russian Federation
China Medical University Hospital
🇨🇳Taichung, Taiwan
Central Clinical Hospital with polyclinic
🇷🇺Moscow, Russian Federation
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Hacettepe Universitesi Tip Fakultesi Hastanesi
🇹🇷Ankara, Turkey
CIUSSS Ouest de l'Ile - St-Mary's Hospital
🇨🇦Montréal, Quebec, Canada
CIUSSS du Nord-de-l'ILe-de-Montreal Hopital du Sacre-Coeur de Montreal
🇨🇦Montréal, Quebec, Canada
Chaim Sheba Medcal Center
🇮🇱Ramat Gan, Israel
FAICIC Clinical Research
🇲🇽Veracruz, Mexico
Southern Cancer Center, PC
🇺🇸Daphne, Alabama, United States
Arizona Oncology Associates PC- HOPE
🇺🇸Tucson, Arizona, United States
Western Regional Medical Center, Inc.
🇺🇸Goodyear, Arizona, United States
Florida Cancer Specialists (North Region)
🇺🇸Saint Petersburg, Florida, United States
Lynn Cancer Institute
🇺🇸Boca Raton, Florida, United States
Florida Cancer Specialists (South Region)
🇺🇸Fort Myers, Florida, United States
PPG-Oncology
🇺🇸Fort Wayne, Indiana, United States
MMCORC
🇺🇸Saint Louis Park, Minnesota, United States
New York Oncology Hematology P.C
🇺🇸Albany, New York, United States
Oncology Hematology Care, Inc.
🇺🇸Cincinnati, Ohio, United States
Southwestern Regional Medical Center, Inc.
🇺🇸Tulsa, Oklahoma, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
St. Luke's Hospital - Anderson Campus
🇺🇸Easton, Pennsylvania, United States
Texas Oncology-Denton South
🇺🇸Denton, Texas, United States
Emily Couric Clinical Cancer Center
🇺🇸Charlottesville, Virginia, United States
Blacktown Hospital
🇦🇺Blacktown, 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, Australia
Lions Gate Hospital
🇨🇦North Vancouver, British Columbia, Canada
CSSS de Laval- Hopital de la Cite de la Sante
🇨🇦Laval, Quebec, Canada
CISSS de la Monteregie-Centre
🇨🇦Greenfield Park, Quebec, Canada
Cairns Base Hospital
🇦🇺Cairns, Queensland, Australia
CHU de Quebec - Hotel-Dieu de Quebec
🇨🇦Quebec, Canada
Zala Megyei Korhaz Pozvai Telephely
ðŸ‡ðŸ‡ºPozva, Zalaegerszeg, Hungary
CIUSSS de la Mauricie-et-du-Centre-du-Quebec
🇨🇦Trois-Rivières, Quebec, Canada
CRU Hungary Kft.
ðŸ‡ðŸ‡ºMiskolc, Hungary
Veszprem Megyei Tudogyogyintezet
ðŸ‡ðŸ‡ºFarkasgyepű, Hungary
Bekes Megyei Pandy Kalman Korhaz
ðŸ‡ðŸ‡ºGyula, Hungary
Ha Emek Medical Center
🇮🇱Afula, Israel
Rambam Medical Center
🇮🇱Haifa, Israel
Soroka Medical Center
🇮🇱Be'er Sheva, Israel
Rabin Medical Center
🇮🇱Petah Tikva, Israel
Centro Di Riferimento Oncologico
🇮🇹Aviano, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
A.O.U. Policlinico Vittorio Emanuele - Presidio Gaspare Rodolico
🇮🇹Catania, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Ospedale San Gerardo - ASST Monza
🇮🇹Monza, Italy
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Medical Care Research S.A. de C.V.
🇲🇽Mérida, Yucatan, Mexico
Oaxaca Site Management Organization S.C.
🇲🇽Oaxaca, Mexico
Udmurtia Republic Regional Clinical Oncology Dispensary
🇷🇺Izhevsk, Russian Federation
Republican Clinical Oncology Dispensary of Tatarstan MoH
🇷🇺Kazan, 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
Tomsk Scientific Research Institute of Oncology
🇷🇺Tomsk, Russian Federation
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 Juan Ramón Jimenez
🇪🇸Huelva, Spain
Hospital Universitario La Fe
🇪🇸Valencia, Spain
Hospital Clinico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
Chang Gung Medical Foundation, Kaohsiung Branch
🇨🇳Kaohsiung, Taiwan
Ege Universitesi Tip Fakultesi Hastanesi
🇹🇷İzmir, Bornova, Turkey
Chang Gung Medical Foundation, Linkou Branch
🇨🇳Taoyuan, Taiwan
North Middlesex Hospital
🇬🇧London, United Kingdom
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Baskent Universitesi Adana Uygulama ve Arastirma Hastanesi
🇹🇷Adana, Turkey
Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi
🇹🇷Adana, Turkey
Western General Hospital
🇬🇧Edinburgh, United Kingdom
Pamukkale Unv. Tip Fak
🇹🇷Denizli, Turkey
Istanbul Universitesi Cerrahpasa Tip Fakultesi
🇹🇷Istanbul, Turkey
Mount Vernon Cancer Centre
🇬🇧Northwood, Middlesex, United Kingdom
Uludag Universitesi Tip Fakultesi
🇹🇷Bursa, Turkey
Samsun Medical Park Hastanesi
🇹🇷Samsun, Turkey
Namık Kemal University Medical Faculty
🇹🇷Tekirdağ, Turkey
Freeman Hospital Newcastle upon Tyne Foundation NHS Trust
🇬🇧Newcastle Upon Tyne, United Kingdom
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Tennessee Oncology, PLLC/The Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Oncology & Hematology Assoc. SW Virginia, Inc., DBA Blue Ridge Cancer Care
🇺🇸Blacksburg, Virginia, United States
Meir Medical Center
🇮🇱Kfar Saba, Israel