Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy in Participants With Triple Negative Breast Cancer (TNBC) (MK-3475-522/KEYNOTE-522)

Triple Negative Breast Neoplasms Clinical Trial

Official title:

A Phase III, Randomized, Double-blind Study to Evaluate Pembrolizumab Plus Chemotherapy vs Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy for Triple Negative Breast Cancer (TNBC)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03036488
• Other study ID #: 3475-522
• Secondary ID: 173567MK-3475-52
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 7, 2017
• Est. completion date: September 30, 2025

Study information

• Verified date: June 2023
• Source: Merck Sharp & Dohme LLC
• 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 (MK-3475) plus chemotherapy vs placebo plus chemotherapy as neoadjuvant therapy and pembrolizumab vs placebo as adjuvant therapy in participants who have triple negative breast cancer (TNBC). After a screening phase of approximately 28 days, each participant will receive neoadjuvant study treatment (Pembrolizumab + Chemotherapy OR Placebo + Chemotherapy) based on the randomization schedule for approximately 24 weeks (8 cycles). Each participant will then undergo definitive surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant study treatment. After definitive surgery, each participant will receive adjuvant study treatment (Pembrolizumab OR Placebo) for approximately 27 weeks (9 cycles). Following adjuvant study treatment, each participant will be monitored for safety, survival and disease recurrence. The primary study hypothesis is that pembrolizumab is superior to placebo, in combination with chemotherapy, as measured by the rate of Pathological Complete Response (pCR) and/or Event-free Survival (EFS), in participants with locally advanced TNBC.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1174
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has newly diagnosed, locally advanced, centrally confirmed TNBC, as defined by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
• Has previously untreated locally advanced non-metastatic (M0) TNBC defined as the following combined primary tumor (T) and regional lymph node (N) staging per current American Joint Committee of Cancer (AJCC) staging criteria for breast cancer as

assessed by the investigator based on radiological and/or clinical assessment:

• T1c, N1-N2
• T2, N0-N2
• T3, N0-N2
• T4a-d, N0-N2
• Provides a core needle biopsy consisting of at least 2 separate tumor cores from the primary tumor at screening to the central laboratory.
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days of treatment initiation.
• Demonstrates adequate organ function.
• Males and female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 12 months after the last dose of study treatment for participants who have received cyclophosphamide, and 6 months after the last dose of study treatment for participants who did not.

Exclusion Criteria:

• Has a history of invasive malignancy =5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• Has received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months.
• Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed death - ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated antigen-4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a pembrolizumab (MK-3475) clinical study.
• Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 4 weeks of the first dose of treatment in this current study.
• Has received a live vaccine within 30 days of the first dose of study treatment.
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (i.e., dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
• Has a known history of Human Immunodeficiency Virus (HIV).
• Has known active Hepatitis B or Hepatitis C.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has significant cardiovascular disease, such as: history of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months OR congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA Class III or IV.
• Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 12 months after the last dose of study treatment for participants who have received cyclophosphamide, and for 6 months after the last dose of study treatment for participants who have not.
• Has a known hypersensitivity to the components of the study treatment or its analogs.
• Has a known history of active tuberculosis (TB, Bacillus Tuberculosis).

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Biological:
• Pembrolizumab
On Day 1 of each cycle in the neoadjuvant and adjuvant phases of the study for a total of 17 cycles; intravenous (IV) infusion.

Drug:
• Carboplatin
On Day 1 of Cycles 1-4 of the neoadjuvant phase of the study OR on Days 1, 8, 15 of Cycles 1-4 of the neoadjuvant phase of the study; IV infusion.
• Paclitaxel
On Days 1, 8 and 15 of Cycles 1-4 in the neoadjuvant phase of the study; IV infusion.
• Doxorubicin
On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.
• Epirubicin
On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.
• Cyclophosphamide
On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV infusion.
• Placebo
normal saline solution or dextrose: On Day 1 of each cycle in the neoadjuvant and adjuvant phases of the study for a total of 17 cycles; IV infusion

Biological:
• Granulocyte colony stimulating factor: Filgrastim or Pegfilgastrim
For prevention of neutropenia, filgrastim 5 µg/kg/day via subcutaneous (SC) injection administered per standard of care after chemotherapy OR pegfilgastrim 100 µg/kg (individualized) or 6 mg (general approach) via SC injection administered per standard of care.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital ( Site 2008)	Adelaide	South Australia
Australia	Cabrini Health ( Site 2009)	East Malvern	Victoria
Australia	Frankston Hospital ( Site 2010)	Franskton
Australia	Royal Brisbane and Women s Hospital ( Site 2003)	Herston
Australia	St John of God Subiaco Hospital ( Site 2006)	Perth
Australia	Royal North Shore Hospital ( Site 2000)	Sydney	New South Wales
Australia	Westmead Hospital ( Site 2002)	Sydney	New South Wales
Brazil	UOPECCAN - Uniao Oeste Paranaense de Estudos e Combate ao Cancer ( Site 0206)	Cascavel
Brazil	Universidade de Caxias do Sul ( Site 0201)	Caxias do Sul
Brazil	Hospital Erasto Gaertner ( Site 0207)	Curitiba
Brazil	Instituto do Cancer do Ceara ( Site 0205)	Fortaleza
Brazil	Hospital Araujo Jorge ( Site 0204)	Goiania
Brazil	Hospital Nossa Senhora da Conceicao ( Site 0203)	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Sao Lucas da PUCRS ( Site 0200)	Porto Alegre
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto ( Site 0208)	Sao Jose do Rio Preto
Brazil	Instituto do Cancer de Sao Paulo - ICESP ( Site 0211)	Sao Paulo
Canada	Tom Baker Cancer Centre ( Site 0105)	Calgary	Alberta
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0106)	Montreal	Quebec
Canada	Jewish General Hospital ( Site 0101)	Montreal	Quebec
Canada	The Ottawa Hospital - Cancer Care ( Site 0100)	Ottawa	Ontario
Canada	CHU de Quebec Universite Laval - Hopital du Saint-Sacrement ( Site 0104)	Quebec
Canada	CIUSSS de l'Estrie-CHUS ( Site 0102)	Sherbrooke	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0103)	Toronto	Ontario
Colombia	Hospital Universitario San Ignacio ( Site 0401)	Bogota
Colombia	Instituto Nacional de Cancerologia [Bogota-Colombia] ( Site 0403)	Bogota
Colombia	Hemato Oncologos S.A. ( Site 0400)	Cali
Colombia	Instituto De Cancerologia S.A. ( Site 0406)	Medellin
Colombia	Oncomedica S.A. ( Site 0404)	Monteria	Cordoba
Colombia	Oncologos del Occidente S.A. ( Site 0405)	Pereira	Risaralda
France	CHU Jean Minjoz ( Site 0917)	Besancon
France	Polyclinique Bordeaux Nord Aquitaine ( Site 0911)	Bordeaux
France	Centre Francois Baclesse ( Site 0907)	Caen
France	Centre Jean Perrin ( Site 0903)	Clermont-Ferrand Cedex 01
France	Clinique Victor Hugo ( Site 0901)	Le Mans
France	Hopital prive du Confluent ( Site 0902)	Nantes
France	Hopital Diaconesses Croix Saint Simon ( Site 0905)	Paris
France	Hopital Saint Louis ( Site 0908)	Paris
France	Institut Curie ( Site 0909)	Paris
France	CHU de la Miletrie Poitiers ( Site 0913)	Poitiers
France	Institut Claudius Regaud IUCT Oncopole ( Site 0914)	Toulouse Cedex 9
Germany	HELIOS Klinikum Berlin-Buch ( Site 1005)	Berlin
Germany	Gynaekologisches Zentrum ( Site 1004)	Bonn
Germany	Universitaetsklinikum Erlangen ( Site 1001)	Erlangen
Germany	Kliniken Essen Mitte ( Site 1012)	Essen
Germany	Universitaetsklinik und Poliklinik Halle/Saale ( Site 1008)	Halle
Germany	Universitaetsklinikum Hamburg-Eppendorf ( Site 1007)	Hamburg
Germany	Klinikum der Universit. Muenchen ( Site 1002)	Muenchen
Germany	Caritasklinik St. Theresia ( Site 1011)	Saarbruecken
Germany	Universitaets-Frauenklinik Tuebingen ( Site 1003)	Tubingen
Ireland	Bon Secours Hospital ( Site 1551)	Cork
Ireland	St Vincents University Hospital ( Site 1550)	Dublin
Israel	Oncology institute ( Site 1601)	Beer Sheva
Israel	Assaf Harofeh MC ( Site 1605)	Beer Yaakov-Zerifin
Israel	Hadassah Ein Karem - Sharett Institute of Oncology ( Site 1600)	Jerusalem
Israel	Rabin-Medical Center ( Site 1604)	Petah Tikva
Israel	Sheba Medical Center ( Site 1602)	Ramat-Gan
Israel	Sourasky Medical Center ( Site 1603)	Tel Aviv
Italy	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia ( Site 1103)	Brescia
Italy	Ospedale San Luca, AZIENDA USL2 TOSCANA NORD OVEST ( Site 1105)	Lucca
Italy	Ospedale Civile di Macerata ( Site 1104)	Macerata
Italy	Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 1101)	Meldola	FC
Italy	Istituto Europeo di Oncologia ( Site 1106)	Milano
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1102)	Napoli
Japan	Chiba Cancer Center ( Site 2519)	Chiba
Japan	Saitama Medical University International Medical Center ( Site 2513)	Hidaka	Saitama
Japan	Hiroshima City Hiroshima Citizens Hospital ( Site 2501)	Hiroshima
Japan	Tokai University Hospital ( Site 2517)	Isehara	Kanagawa
Japan	Social medical corporation Hakuaikai Sagara Hospital ( Site 2508)	Kagoshima
Japan	National Cancer Center Hospital East ( Site 2518)	Kashiwa	Chiba
Japan	St. Marianna University School of Medicine Hospital ( Site 2516)	Kawasaki	Kanagawa
Japan	Saitama Cancer Center ( Site 2510)	Kitaadachi-gun	Saitama
Japan	Kumamoto University Hospital ( Site 2515)	Kumamoto
Japan	Aichi Cancer Center Hospital ( Site 2502)	Nagoya	Aichi
Japan	Hyogo College of Medicine Hospital ( Site 2506)	Nishinomiya	Hyogo
Japan	National Hospital Organization Osaka National Hospital ( Site 2505)	Osaka
Japan	Kindai University Hospital ( Site 2507)	Osakasayama	Osaka
Japan	National Hospital Organization Hokkaido Cancer Center ( Site 2512)	Sapporo	Hokkaido
Japan	Shizuoka Cancer Center Hospital and Research Institute ( Site 2514)	Sunto-gun	Shizuoka
Japan	National Cancer Center Hospital ( Site 2500)	Tokyo
Japan	St.Luke's International Hospital ( Site 2511)	Tokyo
Japan	The Cancer Institute Hospital of JFCR ( Site 2509)	Tokyo
Japan	Toranomon Hospital ( Site 2503)	Tokyo
Korea, Republic of	Asan Medical Center ( Site 2102)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 2103)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 2101)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 2100)	Seoul
Poland	Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1708)	Bydgoszcz
Poland	Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1712)	Bydgoszcz
Poland	Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 1701)	Gdynia
Poland	Centrum Onkologii Instytut im. Marii Sklodowskiej Curie ( Site 1717)	Gliwice	Slaskie
Poland	Centrum Onkologii Instytut im. Marii Sklodowskiej Curie ( Site 1719)	Krakow
Poland	Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli ( Site 1700)	Lublin
Poland	Mazowiecki Szpital Onkologiczny ( Site 1713)	Wieliszew	Mazowieckie
Poland	Dolnoslaskie Centrum Onkologii. ( Site 1702)	Wroclaw
Portugal	Fundacao Champalimaud ( Site 2444)	Lisboa
Portugal	Hospital de Santa Maria, E.P.E. ( Site 2445)	Lisboa
Portugal	Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E. ( Site 2446)	Porto
Russian Federation	Arkhangelsk Clinical Oncological Dispensary ( Site 1810)	Arkhangelsk
Russian Federation	Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1805)	Chelyabinsk
Russian Federation	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1806)	Kazan
Russian Federation	Russian Oncological Research Center n.a. N.N.Blokhin of MoH ( Site 1801)	Moscow
Russian Federation	GBU RO Regional Clinical Oncological Dispensary ( Site 1808)	Ryazan
Russian Federation	Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1803)	Saint Petersburg
Russian Federation	Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1804)	Ufa
Singapore	National Cancer Centre Singapore ( Site 2600)	Singapore
Spain	Hospital del Mar ( Site 1306)	Barcelona
Spain	Hospital General Universitari Vall d Hebron ( Site 1301)	Barcelona
Spain	Instituto Oncologico Baselga.Hospital Quiron. ( Site 1312)	Barcelona
Spain	Hospital Universitario Reina Sofia ( Site 1304)	Cordoba
Spain	ICO L Hospitalet ( Site 1305)	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario Ramon y Cajal ( Site 1300)	Madrid
Spain	Hospital Quiron de Madrid ( Site 1303)	Pozuelo de Alarcon	Madrid
Spain	Complejo Hospitalario Universitario de Santiago ( Site 1308)	Santiago de Compostela
Spain	Hospital Universitario Virgen del Rocio ( Site 1314)	Sevilla
Spain	Hospital Clinico Univ de Valencia ( Site 1313)	Valencia
Sweden	Linkopings Universitetssjukhus ( Site 1402)	Linkoping
Sweden	Karolinska Universitetssjukhuset Solna ( Site 1404)	Solna
Sweden	Norrlands Universitetssjukhus ( Site 1401)	Umea
Sweden	Akademiska Sjukhuset ( Site 1403)	Uppsala
Taiwan	National Cheng Kung University Hospital ( Site 2305)	Tainan
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center ( Site 2304)	Taipei
Taiwan	MacKay Memorial Hospital ( Site 2303)	Taipei
Taiwan	National Taiwan University Hospital ( Site 2301)	Taipei
Taiwan	Taipei Veterans General Hospital ( Site 2302)	Taipei	Beitou
Taiwan	Linkou Chang Gung Memorial Hospital ( Site 2300)	Taoyuan
Turkey	Adana Acibadem Hospital Department of Medical Oncology ( Site 1906)	Adana
Turkey	Baskent University Adana Kisla Hospital ( Site 1903)	Adana
Turkey	Abdurrahman Yurtaslan Oncology Training and Research Hospital ( Site 1909)	Ankara
Turkey	Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1912)	Ankara
Turkey	Ozel Medicana International Ankara Hastanesi ( Site 1915)	Ankara
Turkey	Antalya Memorial Hospital Department of Medical Oncology ( Site 1908)	Antalya
Turkey	Trakya University Medical Faculty Balkan Oncology Hospital ( Site 1901)	Edirne
Turkey	Acibadem Altunizade Hastanesi ( Site 1900)	Istambul
Turkey	Amerikan Hospital Medical ( Site 1902)	Istanbul
Turkey	Istanbul University Cerrahpasa Medical Faculty ( Site 1904)	Istanbul
Turkey	Memorial Sisli Hastanesi ( Site 1913)	Istanbul
Turkey	Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 1905)	Izmir
Turkey	Izmir Medical Park Hospital Department of Medical Oncology ( Site 1907)	Izmir
Turkey	Samsun Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi ( Site 1910)	Samsun	Atakum
United Kingdom	Colchester General Hospital ( Site 1508)	Colchester	Essex
United Kingdom	Barts Cancer Institute ( Site 1500)	London
United Kingdom	St George s Hospital ( Site 1516)	London
United Kingdom	Maidstone Hospital ( Site 1511)	Maidstone
United Kingdom	The James Cook University Hospital ( Site 1515)	Middlesbrough
United Kingdom	Nottingham University Hospitals NHS Trust ( Site 1505)	Nottingham
United Kingdom	Royal Cornwall Hospitals NHS Trust ( Site 1504)	Truro
United States	University of Colorado Cancer Center ( Site 0021)	Aurora	Colorado
United States	Texas Oncology-Austin Central ( Site 8005)	Austin	Texas
United States	University of Virginia ( Site 0022)	Charlottesville	Virginia
United States	The University of Chicago Medical Center ( Site 0047)	Chicago	Illinois
United States	Oncology Hematology Care, Inc. ( Site 8011)	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Good Samaritan Hospital ( Site 0044)	Cincinnati	Ohio
United States	Parkland Health and Hospital System ( Site 0093)	Dallas	Texas
United States	Simmons Cancer Center ( Site 0094)	Dallas	Texas
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 8006)	Dallas	Texas
United States	UT Southwestern Medical Center ( Site 0030)	Dallas	Texas
United States	Henry Ford Hospital ( Site 0003)	Detroit	Michigan
United States	North Shore University Health System ( Site 0081)	Evanston	Illinois
United States	Virginia Cancer Specialists, PC ( Site 8009)	Fairfax	Virginia
United States	Moncrief Cancer Institute ( Site 0092)	Fort Worth	Texas
United States	The West Clinic, P.C. ( Site 0078)	Germantown	Tennessee
United States	Goshen Center for Cancer Care ( Site 0010)	Goshen	Indiana
United States	Houston Methodist Cancer Center ( Site 0013)	Houston	Texas
United States	Texas Oncology-Memorial City ( Site 8003)	Houston	Texas
United States	University of Iowa Hospital and Clinics ( Site 0038)	Iowa City	Iowa
United States	Broome Oncology, LLC ( Site 8002)	Johnson City	New York
United States	Kadlec Clinic Hematology and Oncology ( Site 0087)	Kennewick	Washington
United States	Cedars Sinai Medical Center ( Site 0091)	Los Angeles	California
United States	Univ of Miami-Sylvester Comprehensive Cancer Center- Kendall satellite ( Site 0079)	Miami	Florida
United States	Bon Secours Cancer Institute Medical Oncology at St. Mary's ( Site 0033)	Midlothian	Virginia
United States	Minnesota Oncology Hematology, PA ( Site 8013)	Minneapolis	Minnesota
United States	Pacific Cancer Care ( Site 0069)	Monterey	California
United States	Rutgers Cancer Institute of New Jersey ( Site 0073)	New Brunswick	New Jersey
United States	Yale University School of Medicine ( Site 0054)	New Haven	Connecticut
United States	Christiana Hospital ( Site 0029)	Newark	Delaware
United States	Peninsula Cancer Institute, LLC ( Site 0041)	Newport News	Virginia
United States	Virginia Oncology Associates ( Site 8000)	Norfolk	Virginia
United States	Nyack Hospital Infusion Center ( Site 0059)	Nyack	New York
United States	Magee - Women's Hospital ( Site 0011)	Pittsburgh	Pennsylvania
United States	Texas Oncology- Plano East ( Site 8010)	Plano	Texas
United States	Northwest Cancer Specialists, P.C. ( Site 8008)	Portland	Oregon
United States	Providence Portland Medical Center ( Site 0052)	Portland	Oregon
United States	Rhode Island Hospital ( Site 0060)	Providence	Rhode Island
United States	Texas Oncology-San Antonio Northeast ( Site 8012)	San Antonio	Texas
United States	New England Cancer Specialists ( Site 0005)	Scarborough	Maine
United States	Virginia G. Piper Cancer Center Pharmacy - Scottsdale Healthcare ( Site 0089)	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance ( Site 0068)	Seattle	Washington
United States	Orchard Healthcare Research Inc. ( Site 0049)	Skokie	Illinois
United States	Medical Oncology Associates (Summit Cancer Centers) ( Site 0014)	Spokane	Washington
United States	Arizona Oncology Associates PC- HOPE ( Site 8001)	Tucson	Arizona
United States	Texas Oncology-Tyler ( Site 8007)	Tyler	Texas
United States	ICRI ( Site 0072)	Whittier	California
United States	YVMH dba Vrigina Mason Memorial/North Star Lodge Cancer Center ( Site 8004)	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Colombia,  France,  Germany,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Poland,  Portugal,  Russian Federation,  Singapore,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery	pCR rate (ypT0/Tis ypN0) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery.	Up to approximately 27-30 weeks
Primary	Event-free Survival (EFS) as assessed by Investigator	EFS is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause.	Up to approximately 8 years
Secondary	pCR rate using an alternative definition, ypT0 ypN0 (i.e., no invasive or noninvasive residual in breast or nodes) at the time of definitive surgery	pCR rate (ypT0 ypN0) is defined as the percentage of participants without residual invasive and in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in all participants and in participants with tumors expressing Programmed Death-Ligand 1 (PD-L1).	Up to approximately 27-30 weeks
Secondary	pCR rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery	pCR rate (ypT0/Tis) is defined as the percentage of participants without invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in participants with tumors expressing PD-L1.	Up to approximately 27-30 weeks
Secondary	EFS in participants with tumors expressing PD-L1	EFS is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause.	Up to approximately 8 years
Secondary	pCR rate using an alternative definition, ypT0/Tis (i.e., absence of invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement) at the time of definitive surgery	pCR rate (ypT0/Tis) is defined as the percentage of participants without invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in all participants and in participants with tumors expressing PD-L1.	Up to approximately 27-30 weeks
Secondary	Overall survival (OS)	OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis will be censored at the date of the last follow-up.	Up to approximately 8 years
Secondary	Percentage of participants who experience an adverse event (AE)	An AE is defined as any untoward medical occurrence in a participant administered study treatment which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE.	Up to approximately 61 weeks
Secondary	Percentage of participants who discontinue study treatment due to an AE	An AE is defined as any untoward medical occurrence in a participant administered study treatment which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE.	Up to approximately 57 weeks
Secondary	European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 Questionnaire (QLQ-C30) score	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. The EORTC-QLQ-C30 score will be presented for all participants and for participants with tumors expressing PD-L1.	Up to approximately 27-30 weeks
Secondary	EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR23) score	The EORTC-QLQ-BR23 is a 23-item questionnaire developed to assess the quality of life of breast cancer patients. Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. The EORTC-QLQ-BR23 score will be presented for all participants and for participants with tumors expressing PD-L1.	Up to approximately 27-30 weeks

External Links

•   Merck Clinical Trial Information
•   Plain Language Summary