HER2+ Metastatic Breast Cancer (MBC) Clinical Trial
— NALAOfficial title:
A STUDY OF NERATINIB PLUS CAPECITABINE VERSUS LAPATINIB PLUS CAPECITABINE IN PATIENTS WITH HER2+ METASTATIC BREAST CANCER WHO HAVE RECEIVED TWO OR MORE PRIOR HER2-DIRECTED REGIMENS IN THE METASTATIC SETTING (NALA)
| Verified date | May 2021 |
| Source | Puma Biotechnology, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This is a randomized, multi-center, multinational, open-label, active-controlled, parallel design study of the combination of neratinib plus capecitabine versus the combination of lapatinib plus capecitabine in HER2+ MBC patients who have received two or more prior HER2 directed regimens in the metastatic setting.
| Status | Completed |
| Enrollment | 621 |
| Est. completion date | December 9, 2019 |
| Est. primary completion date | September 28, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Aged =18 years at signing of informed consent. - Histologically confirmed MBC, current stage IV. - Documented HER2 overexpression or gene-amplified tumor immunohistochemistry 3+ or 2+, with confirmatory fluorescence in situ hybridization (FISH) +. - Prior treatment with at least two (2) HER2-directed regimens for metastatic breast cancer. Exclusion Criteria: - Received previous therapy with capecitabine, neratinib, lapatinib, or any other HER2 directed tyrosine kinase inhibitor. Note: There are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria. |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | COIBA Centro de Oncología e Investigación Buenos Aires | Berazategui | Buenos Aires |
| Argentina | Fundación Investigar | Buenos Aires | Ciudad Autónoma De BuenosAires |
| Australia | Bankstown-Lidcombe Hospital | Bankstown | |
| Australia | Sunshine Coast University Hospital | Birtinya | Queensland |
| Australia | St. George Hospital | Kogarah | |
| Australia | Box Hill Hospital, Oncology Department | Melbourne | |
| Australia | Maroondah Hospital, Maroondah Breast Clinic | Melbourne | |
| Australia | The Tweed Hospital | Tweed Heads | New South Wales |
| Australia | Sydney Adventist Hospital | Wahroonga | |
| Austria | University Hospital Innsbruck - Tyrolean Hospital, Department of Gynecology | Innsbruck | |
| Belgium | Our Dear Lady Hospital, Aalst Campus | Aalst | |
| Belgium | Institut Jules Bordet - Medical Oncology | Brussels | |
| Belgium | University Hospital Saint-Luc | Brussels | |
| Belgium | Antwerp University Hospital | Edegem | |
| Belgium | Leuven University Hospitals | Leuven | |
| Belgium | Clinic Saint-Joseph | Liege | |
| Belgium | St. Elizabeth Maternity Clinic | Namur | |
| Belgium | AZ Damiaan General Hospital, Sint-Jozef Oncology Center | Ostend | |
| Belgium | Saint-Augustinus Hospital | Wilrijk | |
| Brazil | Hospital de Cancer de Barretos - Hospital | Barretos | Sao Paulo |
| Brazil | Instituto de Pesquisas Clinicas para Estudos Multicentricos Hospital Geral de Caxias do Sul, Universidade de Caxias do Sul (IPCEM) | Caxias do Sul | Rio Grande Do Sul |
| Brazil | Liga Paranaense de Combate ao Cancer, Hospital Erasto Gaertner | Curitiba | Parana |
| Brazil | Centro Regional Integrado de Oncologia | Fortaleza | Ceara |
| Brazil | Hospital Araújo Jorge, Associação de Combate ao Câncer em Goiás | Goiânia | Goiás |
| Brazil | Instituto Joinvillense de Hematologia e Oncologia | Joinville | Santa Catarina |
| Brazil | Hospital Sao Lucas da PUCRS | Porto Alegre | Rio Grande Do Sul |
| Brazil | Instituto Ribeiraopretano de Combate Ao Cancer - Clinic/Outpatient Facility | Ribeirao Preto | Sao Paulo |
| Brazil | Ensino E Terapia de Inovação Clínica Assistência Multidiciplinar Em Oncologia Ética | Salvador | Bahia |
| Brazil | Núcleo de Oncologia da Bahia - NOB | Salvador | Bahia |
| Brazil | Fundação Faculdade Regional de Medicina de São José do Rio Preto, Hospital de Base | São José Do Rio Preto | São Paulo |
| Brazil | Hospital Do Cancer A C Camargo - Hospital | São Paulo | |
| Brazil | Instituto Brasileiro de Controle Do Câncer IBCC | São Paulo | |
| Canada | Abbotsford Regional Hospital and Cancer Care Centre | Abbotsford | British Columbia |
| Canada | Royal Victoria Regional Health Centre | Barrie | Ontario |
| Canada | Tom Baker Cancer Centre | Calgary | Alberta |
| Canada | British Columbia Cancer Agency | Kelowna | British Columbia |
| Canada | Grand River Hospital | Kitchener | Ontario |
| Canada | CHUM Notre Dame Hospital | Montreal | Quebec |
| Canada | Montreal General Hospital | Montreal | Quebec |
| Canada | Ottawa Hospital, Cancer Center | Ottawa | Ontario |
| Canada | Centre hospitalier affilié universitaire de Québec - Hôpital du Saint-Sacrement | Québec City | Quebec |
| Canada | Fraser Health Authority | Surrey | British Columbia |
| Canada | St. Michael's Hospital | Toronto | Ontario |
| Canada | Sunnybrook Health Sciences Center, Odette Cancer Center | Toronto | Ontario |
| Canada | Toronto East General Hospital | Toronto | Ontario |
| Czechia | Masaryk Memorial Cancer Institute | Brno | |
| Czechia | Hospital Novy Jicin | Novy Jicin | |
| Czechia | University Hospital Motol, Comprehensive Oncology Center | Prague | |
| Denmark | Sjaelland University Hospital | Naestved | |
| Finland | Helsinki University Central Hospital, Department of Oncology | Helsinki | |
| France | Center Jean Perrin | Clermont-Ferrand | |
| France | Saint-Louis Hospital | Paris | |
| France | South Lyon Hospital Center, Department of Clinical Hematology and Medical Oncology | Pierre-Benite | Lyon |
| France | Clinic Sainte Anne, Center for Radiotherapy | Strasbourg | |
| France | Gustave Roussy Oncology Institute, Department of Medicine | Villejuif | |
| Germany | Hematology-Oncology Practice | Augsburg | |
| Germany | Practice for Oncology Bielefeld | Bielefeld | |
| Germany | University Hospital Cologne, Breast Center, Clinic of Obstetrics and Gynecology | Cologne | |
| Germany | University Hospital Schleswig-Holstein | Kiel | |
| Germany | Otto von Guericke University of Magdeburg | Magdeburg | |
| Germany | Onkologie Ravensburg | Ravensburg | |
| Germany | University Hospital Ulm | Ulm | |
| Hong Kong | Queen Elizabeth Hospital, Department of Clinical Oncology | Hong Kong | |
| Hong Kong | Queen Mary Hospital, Department of Clinical Oncology | Hong Kong | |
| Hong Kong | Queen Mary Hospital, Department of Oncology | Hong Kong | |
| Hong Kong | Queen Mary Hospital, Department of Surgery | Hong Kong | |
| Hong Kong | Tuen Mun Hospital | Hong Kong | |
| Hong Kong | Prince of Wales Hospital | Shatin | New Territories |
| Ireland | St. Jame's Hospital | Dublin | |
| Ireland | St. Vincent's University Hospital | Dublin | |
| Israel | Soroka Medical Center | Beersheba | |
| Israel | Rambam Medical Center | Haifa | |
| Israel | Hadassah Medical Center | Jerusalem | |
| Israel | Shaare Zedek Medical Center | Jerusalem | |
| Israel | Meir Medical Center | Kfar-Saba | |
| Israel | Rabin Medical Center, Belinson Hospital | Petah Tikva | |
| Israel | Kaplan Medical Center, Department of Oncology | Rehovot | |
| Israel | Chaim Sheba Medical Center | Tel Hashomer | |
| Israel | Sourasky Medical Center, Department of Oncology | Tel-Aviv | |
| Israel | Ziv Medical Center | Zefat | |
| Italy | Hospital Papa Giovanni XXIII, Department of Medical Oncology | Bergamo | |
| Italy | Hospital Cervesi di Cattolica, Department of Oncology | Cattolica | |
| Italy | University G. D'Annunzio Chieti Pescara | Chieti | |
| Italy | Scientific Institute of Romagna of the Study and Treatment of Cancer | Meldola | |
| Italy | European Institute of Oncology | Milan | |
| Italy | IRCCS - Hospital San Raffaele, Department of Medical Oncology | Milan | |
| Italy | Azienda Ospedaliero San Gerardo | Monza | |
| Italy | National Cancer Institute - IRCCS "Fondazione G. Pascale" | Naples | |
| Italy | Hospital Sacro Cuore Don Calabria, Department of Medical Oncology | Negrar | |
| Italy | Azienda Ospedaliera Regionale San Carlo | Potenza | |
| Italy | Hospital Bianchi Melacrino Morelli | Reggio Calabria | |
| Italy | Hospital Infermi Rimini, Unit of Oncology | Rimini | |
| Italy | National Cancer Institute Regina Elena | Rome | |
| Italy | University Hospital Campus Bio-Medico | Rome | |
| Italy | Institute of Cancer Research and Treatment | Torino | |
| Italy | Hospital Desio and Vimercate, Department of Medical Oncology | Vimercate | |
| Japan | Chiba University Hospital | Chiba-shi | Chiba |
| Japan | JCHO Kurume General Hospital | Fukuoka | |
| Japan | Gunma University Hospital | Gunma | |
| Japan | Hiroshima City Hospital | Hiroshima | |
| Japan | National Hospital Organization Hokkaido Cancer Center | Hokkaido | |
| Japan | Tokai University Hospital | Isehara | Kanagawa |
| Japan | Hakuaikai Medical Corporation Sagara Hospital | Kagoshima-city | |
| Japan | Saitama Cancer Centre | Kitaadachi-gun | Saitama |
| Japan | Kobe City Medical Center General Hospital | Kobe-City | Hyôgo |
| Japan | Kumamoto University Hospital | Kumamoto-shi | Kumamoto |
| Japan | Iwate Medical University Hospital | Morioka | Iwate |
| Japan | Osaka International Cancer Institute | Osaka | |
| Japan | National Hospital Organization Osaka National Hospital | Ôsaka | |
| Japan | Toramonon Hospital | Tokyo | |
| Japan | University of Tsukuba Hospital | Tsukuba | Ibaraki |
| Korea, Republic of | National Cancer Center | Gyeonggi-do | |
| Korea, Republic of | Asan Medical Center | Seoul | |
| Korea, Republic of | Severance Hospital | Seoul | |
| Netherlands | Maastricht University Medical Centre (MUMC) | Maastricht | |
| Portugal | Centro de Investigação Clinica, Hospital da Luz | Lisboa | |
| Portugal | Instituto Portugues de Oncologia de Lisboa Francisco Gentil, EPE | Lisbon | |
| Portugal | Instituto Português de Oncologia do Porto Francisco Gentil, E.P.E. | Porto | |
| Russian Federation | Federal State Government-Financed Institution: City Clinical Hospital #40 | Moscow | Moskva |
| Russian Federation | Russian Oncological Research Center n.a. N.N. Blokhin Russian Academy of Medical Sciences | Moscow | |
| Russian Federation | Tambov Regional Oncological Center | Tambov | |
| Singapore | Gleneagles Medical Centre, Center for Medical Oncology | Singapore | |
| Singapore | Icon Singapore Oncology Consultants Farrer Park Medical Clinic | Singapore | |
| Singapore | Johns Hopkins Singapore International Medical Center | Singapore | |
| Singapore | National Cancer Centre Singapore, Department of Medical Oncology | Singapore | |
| Singapore | National University Hospital | Singapore | |
| Singapore | Parkway Cancer Centre | Singapore | |
| Singapore | Raffles Hospital | Singapore | |
| Spain | Hospital Universitario Vall d'Hebron | Barcelona | |
| Spain | Consorcio Hospitalario Provincial de Castellon | Castellon de la Plana | |
| Spain | Hospital Universitari de Girona Dr. Josep Trueta (ICO Girona), Servicio de Oncologia | Girona | |
| Spain | Complejo Hospitalario Universitario Insular-Materno Infantil | Las Palmas de Gran Canaria | |
| Spain | Centro Integral Oncologico Clara Campal | Madrid | |
| Spain | Centro Oncologico MD Anderson | Madrid | |
| Spain | University Hospital 12 de Octubre, Servicio de Oncologia - Edificio Maternidad, 2ª planta | Madrid | |
| Spain | University Hospital Clinic San Carlos, Servicio de Oncologia Medica | Madrid | |
| Spain | University Hospital Quiron Madrid, Department of Oncology | Madrid | |
| Spain | Hospital Universitario Virgen de la Arrixaca, Servicio de Oncologia | Murcia | |
| Spain | Hospital Son Llatzer, Servicio de Oncologia | Palma de Mallorca | |
| Spain | Hospital Universitario Son Espases | Palma de Mallorca | |
| Spain | Hospital Universitario Virgen Macarena | Sevilla | |
| Spain | University Hospital Virgen del Rocio, Servicio de Oncologia | Sevilla | |
| Spain | Hospital Clinico Universitario de Valencia, Servicio de Oncologia | Valencia | |
| Spain | Hospital Clinico Universitario Lozano Blesa, Servicio de Oncologia | Zaragoza | |
| Sweden | Orebro University Hospital, Department of Oncology | Orebro | |
| Sweden | Uppsala University Hospital, Department of Oncology | Uppsala | |
| Switzerland | Hospital Engeried | Bern | |
| Switzerland | University Hospital of Geneva | Geneva | |
| Switzerland | Canton Hospital Winterthur | Winterthur | |
| Switzerland | Onkozentrum Zurich - Kinik im Park | Zurich | |
| Taiwan | Changhua Christian Hospital | Changhua | Taiwan, Province Of China |
| Taiwan | Buddhist Tzu-Chi General Hospital | Hualien | Taiwan, Province Of China |
| Taiwan | Chung-Ho Memorial Hospital | Kaohsiung | Taiwan, Province Of China |
| Taiwan | Kaohsiung Chang Gung Memorial Hospital | Kaohsiung | Province Of China |
| Taiwan | Kaohsiung Veterans General Hospital | Kaohsiung | Taiwan, Province Of China |
| Taiwan | Taipei Tzu Chi General Hospital | New Taipei City | |
| Taiwan | Kuang Tien General Hospital | Taichung | |
| Taiwan | Taichung Veterans General Hospital, Breast Center | Taichung | Province Of China |
| Taiwan | Chi Mei Medical Center - LiouYing Branch | Tainan | Province Of China |
| Taiwan | Chi Mei Medical Center - YK Branch | Tainan | Province Of China |
| Taiwan | National Cheng Kung University Hospital | Tainan | Province Of China |
| Taiwan | Mackay Memorial Hospital | Taipei | Province Of China |
| Taiwan | National Taiwan University Hospital | Taipei | |
| Taiwan | Taipei Veterans General Hospital | Taipei | |
| Taiwan | Tri-Service General Hospital | Taipei | Province Of China |
| Turkey | Ege University | Bornova | Izmir |
| Turkey | Marmara University Faculty of Medicine | Istanbul | |
| United Kingdom | Queen Elizabeth Hospital Birmingham | Birmingham | West Midlands |
| United Kingdom | Velindre Cancer Centre | Cardiff | |
| United Kingdom | Colchester General Hospital | Colchester | Essex |
| United Kingdom | Calderdale Royal Hospital, Macmillan Unit | Halifax | |
| United Kingdom | Huddersfield Royal Infirmary | Huddersfield | |
| United Kingdom | Nottingham City Hospital Campus, Department of Oncology | Nottingham | |
| United States | UCLA Hematology Oncology | Alhambra | California |
| United States | Emory Clinic | Atlanta | Georgia |
| United States | Emory University Hospital Midtown | Atlanta | Georgia |
| United States | Emory University Winship Cancer Institute | Atlanta | Georgia |
| United States | CBCC Global Research, Inc. at Comprehensive Blood and Caner Center | Bakersfield | California |
| United States | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital | Baltimore | Maryland |
| United States | Dana Farber Cancer Institute | Boston | Massachusetts |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | Ironwood Cancer and Research Centers | Chandler | Arizona |
| United States | Resurrection Medical Group | Chicago | Illinois |
| United States | Cleveland Clinic Taussig Cancer Center | Cleveland | Ohio |
| United States | University Hospitals Cleveland Medical Center | Cleveland | Ohio |
| United States | North Shore Oncology-Hematology Associates, Ltd. | Crystal Lake | Illinois |
| United States | University of Texas Southwestern Medical Center | Dallas | Texas |
| United States | University of Texas Southwestern Medical Center at Dallas | Dallas | Texas |
| United States | Karmanos Cancer Institute | Detroit | Michigan |
| United States | North Shore Hematology Oncology Association PC | East Setauket | New York |
| United States | Compassionate Cancer Care Medical Group Inc. | Fountain Valley | California |
| United States | St. Jude Heritage Medical Group | Fullerton | California |
| United States | St. Jude Heritage Medical Group | Fullerton | California |
| United States | West Clinic PC | Germantown | Tennessee |
| United States | Ironwood Cancer and Research Centers | Gilbert | Arizona |
| United States | Marin Cancer Care, Inc. | Greenbrae | California |
| United States | UPMC Cancer Pavillion | Greensburg | Pennsylvania |
| United States | Primary Healthcare Associates, SC | Harvey | Illinois |
| United States | Hershey Medical Center | Hershey | Pennsylvania |
| United States | North Shore Hematology Oncology | Highland Park | Illinois |
| United States | Primary Health Oncology | Hobart | Indiana |
| United States | St. Mary Medical Center | Hobart | Indiana |
| United States | OnCare Hawaii | Honolulu | Hawaii |
| United States | Queen's Medical Center | Honolulu | Hawaii |
| United States | Straub Clinic and Hospital | Honolulu | Hawaii |
| United States | University of Hawaii Cancer Center | Honolulu | Hawaii |
| United States | UCLA Hematology Oncology | Irvine | California |
| United States | University of California San Diego Medical Center | La Jolla | California |
| United States | University of California San Diego Moores Cancer Center | La Jolla | California |
| United States | Clinical Research Alliance | Lake Success | New York |
| United States | NYU Langone Medical Center | Lake Success | New York |
| United States | North Shore Oncology-Hematology Associates, Ltd. | Libertyville | Illinois |
| United States | Sidney Kimmel Comprehensive Cancer Center at John Hopkins at Greenspring Station | Lutherville | Maryland |
| United States | West Clinic PC | Memphis | Tennessee |
| United States | Ironwood Cancer and Research Centers | Mesa | Arizona |
| United States | UPMC Cancer Pavillion | Monroeville | Pennsylvania |
| United States | Community Hospital | Munster | Indiana |
| United States | Cancer Institute of New Jersey | New Brunswick | New Jersey |
| United States | Clinical Research Alliance, Inc. | New York | New York |
| United States | Weill Cornell Medical College | New York | New York |
| United States | Breastlink Medical Group, Inc. | Orange | California |
| United States | University Hospitals Case Medical Center | Orange Village | Ohio |
| United States | UCLA Hematology Oncology | Pasadena | California |
| United States | Hillman Cancer Center | Pittsburgh | Pennsylvania |
| United States | Magee Women's Hospital | Pittsburgh | Pennsylvania |
| United States | UPMC Cancer Pavillion | Pittsburgh | Pennsylvania |
| United States | UPMC Cancer Pavillion | Pittsburgh | Pennsylvania |
| United States | Broward Medical Oncology Office | Plantation | Florida |
| United States | Florida Cancer Research Institute | Plantation | Florida |
| United States | UCLA Hematology Oncology | Porter Ranch | California |
| United States | Emad Ibrahim, MD | Redlands | California |
| United States | Cancer Care Associates Medical Group, Inc | Redondo Beach | California |
| United States | Compassionate Cancer Care Medical Group | Riverside | California |
| United States | Siteman Cancer Center - South County | Saint Louis | Missouri |
| United States | Siteman Cancer Center - West County | Saint Louis | Missouri |
| United States | Washington University in St. Louis | Saint Louis | Missouri |
| United States | Siteman Cancer Center - St. Peters | Saint Peters | Missouri |
| United States | Sharp Memorial Hospital | San Diego | California |
| United States | University of California San Diego Medical Center - Hillcrest | San Diego | California |
| United States | Breastlink Medical Group, Inc. | Santa Ana | California |
| United States | Cancer Center of Santa Barbara Sansum Clinic | Santa Barbara | California |
| United States | Central Coast Medical Oncology | Santa Maria | California |
| United States | UCLA Hematology Oncology | Santa Monica | California |
| United States | Ironwood Cancer and Research Centers | Scottsdale | Arizona |
| United States | Orchard Healthcare Research Inc | Skokie | Illinois |
| United States | Cancer Center of Santa Barbara | Solvang | California |
| United States | The Cancer Institute at University of Maryland St. Joseph Medical Center | Towson | Maryland |
| United States | UPMC Cancer Pavillion | Uniontown | Pennsylvania |
| United States | UCLA Healthcare Santa Clarita Oncology | Valencia | California |
| United States | Sibley Memorial Hospital | Washington | District of Columbia |
| United States | UPMC Cancer Pavillion | West Mifflin | Pennsylvania |
| United States | UCLA Hematology/Oncology | Westlake Village | California |
| Lead Sponsor | Collaborator |
|---|---|
| Puma Biotechnology, Inc. |
United States, Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, Denmark, Finland, France, Germany, Hong Kong, Ireland, Israel, Italy, Japan, Korea, Republic of, Netherlands, Portugal, Russian Federation, Singapore, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Centrally Assessed Progression Free Survival | Progression Free Survival (PFS), Measured in Months, for Randomized Subjects of the Central Assessment. The time interval from the date of randomization until the first date on which recurrence, progression (per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) v1.1), or death due to any cause, is documented. For subjects without recurrence, progression or death, it is censored at the last valid tumor assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Here, the time to event was reported as the restricted mean survival time. The restricted mean survival time was defined as the area under the curve of the survival function up to 24 months. | From randomization date to recurrence, progression or death, assessed up to 38 months. The result is based on primary analysis data cut. | |
| Primary | Overall Survival | Overall survival (OS) is defined as the time from randomization to death due to any cause, censored at the last date known alive on or prior to the data cutoff employed for the analysis, whichever was earlier. Here, the time to event was reported as the restricted mean survival time. The restricted mean survival time was defined as the area under the curve of the survival function up to 48 months. | From randomization date to death, assessed up to 59 months.The result is based on primary analysis data cut. | |
| Secondary | Intervention for Symptomatic Metastatic Central Nervous System Disease | Intervention for symptomatic metastatic central nervous system disease is defined as the time from randomization to the first start date of an intervention for symptomatic metastatic CNS disease. Subjects that do not have an intervention for symptomatic metastatic CNS and do not die will be censored at the last date known alive on or prior to the data cutoff. Deaths are treated as competing events. Percentage of participants with intervention for CNS, estimated by cumulative incidence methods. Cumulative incidence methods are the standard way to estimate incidence of an endpoint in the presence of competing risks and censoring. | From randomization date to first intervention for symptomatic metastatic CNS disease, assessed up to 59 months.The result is based on primary analysis data cut. | |
| Secondary | Objective Response Rate (ORR) - Central Assessment (ITT Population With Measurable Disease at Screening) | Objective response rate is defined as the percentage of participants demonstrating an objective response during the study. Objective response includes confirmed complete responses (CR) and partial responses (PR) as defined in the RECIST criteria included in the study protocol. The ORR is for Central Assessment for subjects that had measurable disease at screening. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | From randomization date to first confirmed Complete or Partial Response, whichever came earlier, up to 42 months.The result is based on primary analysis data cut. | |
| Secondary | Clinical Benefit Rate (CBR) - Central Assessment (ITT Population With Measurable Disease at Screening) | Clinical benefit rate is the percentage of participants who achieve overall tumor response (confirmed CR or PR) or stable disease (SD) lasting for at least 24 weeks from randomization. The CBR was for Central Assessment for subjects who had Measurable Disease at Screening. | From randomization date to either first confirmed CR or PR or Stable Disease, whichever came earlier, up to 42 months.The result is based on primary analysis data cut. | |
| Secondary | Duration of Response (DOR) - Central Assessment (Population That Had a Response With Measurable Disease at Screening) | The Duration of Response (DOR) is for Central Assessment for the Population that Had a Response with Measurable Disease at Screening. Duration of response is measured from the time at which measurement criteria are first met for CR or PR (whichever status is recorded first) until the first date of recurrence or progressive disease (PD) or death is objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, per RECIST v1.1. This value is censored at the last valid tumor assessment if PD or death has not been documented. |
From start date of response after randomization to first PD, up to 33 months.The result is based on primary analysis data cut. | |
| Secondary | Percentage of Participants With Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events) | Adverse Events to be measured are Treatment-Emergent and Serious AEs that occurred on or after first dose of investigational product and up to 28 days after the last dose | From first dose through last dose + 28 days, up to 41 months. The result is based on final data cut. |