Pembrolizumab Plus Epacadostat vs Pembrolizumab Plus Placebo in Metastatic Non-Small Cell Lung Cancer (KEYNOTE-654-05/ECHO-305-05)
- Registration Number
- NCT03322540
- Lead Sponsor
- Incyte Corporation
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 154
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab + Epacadostat Epacadostat Participants received pembrolizumab 200 mg as an intravenous (IV) infusion, every three weeks (Q3W) starting on Day 1 of each cycle for up to 35 administrations in combination with epacadostat 100 mg orally, twice daily. Epacodostat administration was discontinued after the implementation of protocol amendment 05. Pembrolizumab + Placebo Placebo Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05. Pembrolizumab + Epacadostat Pembrolizumab Participants received pembrolizumab 200 mg as an intravenous (IV) infusion, every three weeks (Q3W) starting on Day 1 of each cycle for up to 35 administrations in combination with epacadostat 100 mg orally, twice daily. Epacodostat administration was discontinued after the implementation of protocol amendment 05. Pembrolizumab + Placebo Pembrolizumab Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) of Pembrolizumab Plus Epacadostat Versus Pembrolizumab Plus Placebo Up to approximately 6 months 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).
- Secondary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) Up to 37 months 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.
Progression-free Survival (PFS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo Up to approximately 36 months 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.
Overall Survival (OS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo Up to approximately 36 months OS is defined as the time from randomization to death due to any cause.
Duration of Response (DOR) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo Up to approximately 36 months 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.
Number of Participants Who Discontinued Study Drug Due to AEs Up to 37 months 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.
Trial Locations
- Locations (99)
Anne Arundel Health System Research Institute
🇺🇸Annapolis, Maryland, United States
Maryland Oncology Hematology, P.A.
🇺🇸Rockville, Maryland, United States
Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Rigshospitalet
🇩🇰Copenhagen, Denmark
Rambam Medical Center
🇮🇱Haifa, Israel
Innovative Clinical Research Institute
🇺🇸Whittier, California, United States
Southeastern Regional Medical Center, Inc.
🇺🇸Newnan, Georgia, United States
Tennessee Oncology, PLLC/The Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Sault Area Hospital
🇨🇦Sault Ste Marie, Ontario, Canada
Florida Cancer Specialists (North Region)
🇺🇸Saint Petersburg, Florida, United States
Texas Oncology-South Austin
🇺🇸Austin, Texas, United States
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Regionshospitalet Herning
🇩🇰Herning, Denmark
Hospital General de Alicante
🇪🇸Alicante, Spain
Erciyes Universitesi Tip Fakultesi
🇹🇷Kayseri, Turkey
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
Hospital Clinico de Valencia
🇪🇸Valencia, Spain
Leeds Teaching Hospital NHS Trust. St. James University Hospital
🇬🇧Leeds, United Kingdom
Basken Uni. Adana Dr.Turgut Noyan Uygulama ve Arastirma Merkezi
🇹🇷Adana, Turkey
Chungbuk National University Hospital
🇰🇷Cheongju si, Chungcheongbuk Do, Korea, Republic of
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Niigata Cancer Center Hospital
🇯🇵Niigata, Japan
IRCCS A.O.U. San Martino - IST
🇮🇹Genova, Italy
Akdeniz Universitesi Tip Fakultesi
🇹🇷Antalya, Turkey
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Ankara University Medical Faculty
🇹🇷Ankara, Turkey
Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi
🇹🇷Konya, Turkey
Florida Cancer Specialists (South Region)
🇺🇸Fort Myers, Florida, United States
Weinberg Cancer Institute at Franklin Square
🇺🇸Baltimore, Maryland, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Minnesota Oncology Hematology, PA
🇺🇸Coon Rapids, Minnesota, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Pacific Cancer Medical Center, Inc.
🇺🇸Anaheim, California, United States
MI Odessa Regional Oncological Centre
🇺🇦Odesa, Ukraine
Kurume University Hospital
🇯🇵Kurume, Fukuoka, Japan
Kindai University Hospital
🇯🇵Osakasayama, Osaka, Japan
Gacheon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Institut Kanser Negara - National Cancer Institute
🇲🇾Putrajaya, Wilayah Persekutuan, Malaysia
Sarawak General Hospital
🇲🇾Kuching, Malaysia
Przychodnia Lekarska Komed
🇵🇱Konin, Poland
MI Kryviy Rih Center of Dnipropetrovsk Regional Council
🇺🇦Kryvyi Rih, Dnipropetrovsk Region, Ukraine
Zaporizhzhya Regional Clinical Oncology Center
🇺🇦Zaporizhzhya, Ukraine
St John of God Murdoch Medical Clinic
🇦🇺Murdoch, Western Australia, Australia
Odense Universitetshospital
🇩🇰Odense, Denmark
Moncton Hospital - Horizon Health Network
🇨🇦Moncton, New Brunswick, Canada
Soroka Medical Center
🇮🇱Beer Sheva, Israel
Kanagawa Cancer Center
🇯🇵Yokohama, Kanagawa, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
St Vincents University Hospital
🇮🇪Dublin, Ireland
Austin Health-Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Meir Medical Center
🇮🇱Kfar Saba, Israel
Kansai Medical University Hospital
🇯🇵Hirakata, Osaka, Japan
Nippon Medical School Hospital
🇯🇵Tokyo, Japan
SA Tartu Ulikooli Kliinikum
🇪🇪Tartu, Estonia
Galway University Hospital
🇮🇪Galway, Connacht, Ireland
Rabin Medical Center
🇮🇱Petah Tikva, Israel
Sendai Kousei Hospital
🇯🇵Sendai, Miyagi, Japan
National Hospital Organization Nagoya Medical Center
🇯🇵Nagoya, Aichi, Japan
National Hospital Organization Shikoku Cancer Center
🇯🇵Matsuyama, Ehime, Japan
Hospital Tengku Ampuan Afzan
🇲🇾Kuantan, Pahang, Malaysia
Kanazawa University Hospital
🇯🇵Kanazawa, Ishikawa, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Japan
Shizuoka Cancer Center
🇯🇵Nagaizumi-chō, Shizuoka Prefecture, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Pantai Hospital Kuala Lumpur
🇲🇾Kuala Lumpur, Malaysia
Belgorod Regional Oncology Dispensary
🇷🇺Belgorod, Russian Federation
Kantonsspital Winterthur
🇨🇭Winterthur, Switzerland
Kyiv City Clinical Oncological Center
🇺🇦Kyiv, Ukraine
Central Clinical Hospital with polyclinic
🇷🇺Moscow, Russian Federation
Wakayama Medical University Hospital
🇯🇵Wakayama, Japan
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc
🇵🇱Olsztyn, Poland
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, Russian Federation
Oncological Institute of Southern Switzerland
🇨🇭Bellinzona, Switzerland
Hospital Alvaro Cunqueiro
🇪🇸Vigo, Pontevedra, Spain
Swietokrzyskie Centrum Onkologii SPZOZ
🇵🇱Kielce, Poland
Centrum Onkologii. Instytut im. Marii Sklodowskiej-Curie
🇵🇱Gliwice, Poland
Moscow Research Oncology Institute named after P.A. Hertsen
🇷🇺Moscow, Russian Federation
Centrum Onkologii im. Prof. Franciszka Lukaszczyka
🇵🇱Bydgoszcz, Poland
Wojewodzki Szpital im. Zofii z Zamoyskich Tarnowskiej w Tarnobrzegu
🇵🇱Tarnobrzeg, Poland
Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie
🇵🇱Warszawa, Poland
Inselspital Universitatsspital Bern
🇨🇭Bern, Switzerland
Universitaetsspital Zuerich
🇨🇭Zuerich, Switzerland
Hopitaux Universitaires de Geneve HUG.
🇨🇭Geneva, Switzerland
Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC
🇺🇦Dnipropetrovsk, Ukraine
Dobryi Prognoz
🇺🇦Kyiv, Ukraine
Grigoriev Institute for medical Radiology NAMS of Ukraine
🇺🇦Kharkiv, Ukraine
PP PPC Acinus Medical and Diagnostic Centre
🇺🇦Kirovohrad, Ukraine
Volyn Regional Oncological Dispensary
🇺🇦Lutsk, Ukraine
William Osler Health System
🇨🇦Brampton, Ontario, Canada
Cancer Centre of Southeastern Ontario at Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
Hospital del Mar
🇪🇸Barcelona, Spain
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada