A Study to Evaluate the Efficacy and Safety of Giredestrant in Combination With Phesgo (Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf) Versus Phesgo in Participants With Locally Advanced or Metastatic Breast Cancer (heredERA Breast Cancer)

Locally Advanced or Metastatic Breast Cancer Clinical Trial

Official title:

A Phase III, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Giredestrant in Combination With Phesgo Versus Phesgo After Induction Therapy With Phesgo + Taxane in Patients With Previously Untreated HER2-Positive, Estrogen Receptor-Positive Locally-Advanced or Metastatic Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05296798
• Other study ID #: WO43571
• Secondary ID: 2022-500014-26-0
• Status: Recruiting
• Phase: Phase 3
• Start date: July 4, 2022
• Est. completion date: September 30, 2032

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: WO43571 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase III, randomized, two-arm, open-label, multicenter study will evaluate the efficacy and safety of giredestrant plus Phesgo compared with Phesgo after induction therapy with Phesgo plus taxane in participants with human epidermal growth factor receptor 2 (HER2)-positive, estrogen receptor (ER)-positive advanced breast cancer (metastatic or locally advanced disease not amenable to curative treatment) who have not previously received a systemic non-hormonal anti-cancer therapy in the advanced setting.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 812
• Est. completion date: September 30, 2032
• Est. primary completion date: August 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed and documented human epidermal growth factor receptor 2 (HER2)-positive/estrogen receptor (ER)-positive adenocarcinoma of the breast with metastatic or locally-advanced disease not amenable to curative resection
• At least one measurable lesion and/or non-measurable disease evaluable according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence of =6 months
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Left ventricular ejection fraction (LVEF) of at least (=)50% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
• Adequate hematologic and end-organ function
• For women of childbearing potential: Participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agree to refrain from donating eggs, during the treatment period and for 7 months after the final dose of Phesgo
• For men: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm, during the treatment period and for 7 months after the final dose of Phesgo to avoid exposing the embryo Maintenance Phase Inclusion Criteria
• Complete a minimum of four cycles of induction therapy
• Achieve a minimum of stable disease (SD) (or Non-complete response [CR]/Non-progressive disease [PD] for participants with non-measurable disease) (i.e., did not experience PD) according to RECIST v1.1 at the last tumor assessment during the induction therapy phase
• LVEF of =50% at the last assessment during the induction therapy phase

Exclusion Criteria:

• Previous systemic non-hormonal anti-cancer therapy in the metastatic breast cancer (MBC) or advanced breast cancer (ABC) setting. Note: Up to one line of single-agent endocrine therapy given in the metastatic or locally advanced setting will be allowed.
• Prior treatment with a selective estrogen receptor degrader (SERD)
• Previous treatment with approved or investigative anti-HER2 agents in any breast cancer treatment setting, except Phesgo (or trastuzumab SC with pertuzumab IV, or pertuzumab and trastuzumab IV), single-agent trastuzumab IV or SC, ado-trastuzumab emtansine, lapatinib, and neratinib in the neoadjuvant or adjuvant setting
• Disease progression within 6 months of receiving adjuvant anti-HER2 therapy (such as trastuzumab, with or without pertuzumab [IV, SC, or fixed-dose combination], or ado-trastuzumab emtansine, or neratinib)
• Non-resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) Grade 1 or better
• History of persistent Grade =2 (NCI-CTC, Version 5.0) hematological toxicity resulting from previous adjuvant or neo-adjuvant therapy
• History of exposure to the following cumulative doses of anthracyclines; Doxorubicin >360 mg/m2; Liposomal doxorubicin >500 mg/m2; Epirubucin >720 mg/m2; Mitoxantrone >120 mg/m2; Idarubicin >90 mg/m2.
• Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease
• Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the final dose of Phesgo (Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of induction therapy).
• Treated with investigational therapy within 28 days prior to initiation of induction therapy
• Treated with localized palliative radiotherapy within 14 days prior to initiation of induction therapy
• Concurrent participation in any other therapeutic clinical trial
• Known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies
• Current chronic daily treatment (continuous for >3 months) with corticosteroids (dose of 10 mg/day methylprednisolone or equivalent)
• Poorly controlled hypertension
• Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, active liver disease including active viral or other hepatitis virus, autoimmune hepatic disorders, or sclerosing cholangitis, current alcohol abuse, or cirrhosis
• Active cardiac disease or history of cardiac dysfunction
• Major surgical procedure or significant traumatic injury within 14 days prior to enrollment or anticipation of need for major surgery during induction therapy
• Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal surgery
• Concurrent, serious, uncontrolled infections, or known infection with HIV with the following exception: Individuals who are HIV positive are eligible provided they are stable on anti-retroviral therapy for =4 weeks, have a CD4 count =350 cells/uL, and have an undetectable viral load and no history of AIDS-defining opportunistic infections within 12 months prior to enrollment.
• Serious COVID-19 infection within 14 days prior to enrollment; however, no screening testing for SARS-CoV-2 is required
• Serious infection requiring oral or IV antibiotics within 7 days prior to screening
• Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in the study
• History of malignancy within 5 years prior to screening with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death
• For pre- and perimenopausal women, and men: Known hypersensitivity to luteinizing hormone-releasing hormone agonist (LHRHa); Not willing to undergo and maintain treatment with approved LHRHa therapy for the duration of endocrine therapy that requires gonadal function suppression
• Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of giredestrant treatment in Arm B
• A documented history of hemorrhagic diathesis, coagulopathy, or thromboembolism, including deep vein thrombosis, unless the condition is adequately treated and under control

Related Conditions & MeSH terms

• Breast Neoplasms
• Locally Advanced or Metastatic Breast Cancer

Intervention

Drug:
• Phesgo
Phesgo will be administered subcutaneously (SC) at a fixed non-weight-based dose. In the induction therapy phase, a loading dose (1200 milligram (mg) pertuzumab, 600 mg trastuzumab, and 30,000 units of recombinant human PH20 hyaluronidase [rHuPH20]) will be administered in the first cycle (1 cycle is 21 days). In subsequent cycles, maintenance doses (600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units rHuPH20) will be administered once every 3 weeks (Q3W).
• Giredestrant
A 30 milligram (mg) capsule of giredestrant will be taken orally once a day on Days 1 to 21 of each 21-day cycle.
• Docetaxel
During the induction therapy phase, the investigator's choice of taxane-based chemotherapy (i.e., docetaxel or paclitaxel) will be administered after Phesgo. Docetaxel will be administered at 75 milligrams per metre squared of body surface area (mg/m2) intravenously over 60 (±10) minutes on Day 1 of each cycle for 4 to 8 cycles (a cycle is 21 days); this dose may be escalated to 100 mg/m2 if the initial dose was well tolerated.
• Paclitaxel
During the induction therapy phase, the investigator's choice of taxane-based chemotherapy (i.e., docetaxel or paclitaxel) will be administered after Phesgo. Paclitaxel will be administered at 80 milligrams per metre squared of body surface area (mg/m2) intravenously over a minimum of 1 hour on Days 1, 8, and 15 of each cycle for 4 to 8 cycles (a cycle is 21 days); this weekly regimen is considered as one complete cycle whenever 3 weekly doses are given.
• LHRH Agonist
A luteinizing hormone-releasing hormone (LHRH) agonist will be administered every 28 days to pre- and peri-menopausal women and all male participants while receiving giredestrant in Arm B. An LHRH agonist may be administered to male participants and pre- and peri-menopausal female participants receiving tamoxifen in Arm A, and should be administered to those receiving an aromatase inhibitor in Arm A. The investigator will determine and supply the appropriate LHRH agonist locally approved for use in breast cancer. The LHRH agonist will be administered according to local prescribing information.
• Optional Endocrine Therapy of Investigator's Choice
For participants in Arm A, optional endocrine therapy of investigator's choice is allowed based on the standard of care, and it can include an aromatase inhibitor or tamoxifen with or without an LHRH agonist, or gonadal ablation. The decision to include or exclude this option must be made prior to randomization.

Locations

Country	Name	City	State
Argentina	Fundación CENIT para la Investigación en Neurociencias	Buenos Aires
Argentina	Centro Oncologico Korben; Oncology	Ciudad Autonoma Buenos Aires
Argentina	Centro Oncologico Riojano Integral (CORI)	La Rioja
Argentina	Fundacion Scherbovsky	Mendoza
Argentina	Hospital Provincial del Centenario	Rosario
Argentina	Instituto de Oncología de Rosario	Rosario
Argentina	CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica	San Juan
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	GHdC Site Notre Dame	Charleroi
Belgium	UZ Gent	Gent
Belgium	Jessa Zkh (Campus Virga Jesse)	Hasselt
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	Clinique Ste-Elisabeth	Namur
Brazil	Fundação Pio XII Hospital de Câncer de Barretos	Barretos	SP
Brazil	Pronutrir - suporte nutricional e quimioterapia ltda.	Fortaleza	CE
Brazil	Hospital Araujo Jorge; Departamento de Ginecologia E Mama	Goiania	GO
Brazil	Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda	Ijui	RS
Brazil	Hospital do Câncer de Londrina	Londrina	PR
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Hospital do Cancer de Pernambuco - HCP	Recife	PE
Brazil	Hospital Sao Rafael - HSR	Salvador	BA
Brazil	Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda	Sao Paulo	SP
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
China	Affiliated Hospital of Hebei University; Department of medical oncology	Baoding
China	Peking University People's Hospital	Beijing
China	the First Affiliated Hospital of Bengbu Medical College	Bengbu City
China	The First Hospital of Jilin University	Changchun City
China	Hunan Cancer Hospital	Changsha CITY
China	Sichuan Cancer Hospital	Chengdu City
China	West China Hospital - Sichuan University	Chengdu City
China	Fujian Cancer Hospital	Fuzhou
China	No. 900 Hospital (Fuzhou General Hospital)	Fuzhou City
China	Zhejiang Provincial People?s Hospital	Hangzhou
China	Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department	Hangzhou City
China	Shandong Cancer Hospital	Jinan
China	The First Affiliated Hospital Of Jinzhou Medical University	Jinzhou City
China	Yunnan Cancer Hospital	Kunming
China	Jiangxi Cancer Hospital	Nanchang City
China	The Third Hospital of Nanchang	Nanchang City
China	Jiangsu Cancer Hospital	Nanjing City
China	Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)	Nanjing City
China	Guangxi Cancer Hospital of Guangxi Medical University	Nanning City
China	Liaoning Provincial Cancer Hospital	Shengyang
China	The First Affiliated Hospital of China Medical University	Shenyang City
China	Tianjin Cancer Hospital	Tianjin
China	The Tumor Hospital of Xinjiang Medical University	Urumqi
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
China	The First Affiliated Hospital of Xian Jiao Tong University	Xi'an City
Colombia	Clinica De La Costa	Barranquilla
Colombia	Clinica Colsanitas S.A. sede Clinica Universitaria Colombia	Bogota, D.C.
Colombia	Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo	Bogota, D.C.
Colombia	Oncomedica S.A.	Monteria
Colombia	Oncólogos de Occidente	Pereira
France	Institut Sainte Catherine;Recherche Clinique	Avignon
France	CH de la Côte Basque - Hôpital de Bayonne	Bayonne
France	CHU Besançon - Hôpital Jean Minjoz	Besançon Cedex
France	Polyclinique Bordeaux Nord Aquitaine; Chimiotherapie Radiotherapie	Bordeaux
France	CHU de GRENOBLE	Grenoble
France	CHD Vendée	La Roche Sur Yon
France	Hopital Prive Jean Mermoz	Lyon
France	INSTITUT CURIE_Site Paris	Paris
France	Centre Catalan D' Oncologie	Perpignan
Germany	Gesundheitszentrum Wetterau, Hochwaldkrankenhaus Bad Nauheim; Gynäkologie/ onkolog. Tagesklinik	Bad Nauheim
Germany	Sozialstiftung Bamberg, Klinikum am Bruderwald, Gynäkologie	Bamberg
Germany	Onkologische Schwerpunktpraxis Kurfürstendamm	Berlin
Germany	Gynäkologisches Zentrum Bonn	Bonn
Germany	Onkozentrum Dres. Göhler	Dresden
Germany	Kliniken Essen-Mitte	Essen
Germany	Universitätsklinikum Freiburg; Frauenklinik	Freiburg
Germany	HOPA MVZ GmbH	Hamburg
Germany	Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg	Heidelberg
Germany	Ärztehaus am Bahnhofsplatz; Praxis Uleer/Pourfard	Hildesheim
Germany	Universitätsklinikum des Saarlandes; Klinik f. Frauenheilkunden und Geburtshilfe	Homburg/Saar
Germany	Dres. Andreas Köhler und Roswitha Fuchs	Langen
Germany	Studienzentrum Onkologie Ravensburg GbR; Onkologie Ravensburg	Ravensburg
Germany	Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie	Trier
Hungary	Budapesti Szent Margit Korhaz; Onkologia Osztaly	Budapest
Hungary	Eszak-Pesti Centrumkorhaz - Honvedkorhaz; Podmaniczky utcai telephely	Budapest
Hungary	Bekes Varmegyei Központi Korhaz, Pandy Kalman Tagkorhaz; Onkologiai Központ	Gyula
Hungary	Somogy Varmegyei Kaposi Mor Oktato Korhaz; Onkologiai Osztaly	Kaposvár
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet; Megyei Onkologiai Kozpont	Szolnok
Hungary	Komarom-Eszergom Varmegyei Szent Borbala Korhaz; Onkologiai Osztaly	Tatabanya
India	Manipal Hospital; Department of Oncology	Bangalore	Karnataka
India	TATA Medical Centre; Medical Oncology	Kolkata	WEST Bengal
India	Tata Memorial Hospital; Dept of Medical Oncology	Mumbai	Maharashtra
India	Fortis Hospital	New Delhi	Delhi
India	Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology	New Delhi	Delhi
India	Sahyadri Super Specialty Hospital Hadapsar	Pune	Maharashtra
Italy	ASST DEGLI SPEDALI CIVILI DI BRESCIA; Oncologia Medica	Brescia	Lombardia
Italy	Ospedale Civile; Unita Operativa Di Oncologia Medica	Livorno	Toscana
Italy	Istituto Europeo Di Oncologia	Milano	Lombardia
Italy	Humanitas Centro Catanese Di Oncologia; Oncologia Medica	Misterbianco (CT)	Sicilia
Italy	Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica	Napoli	Campania
Italy	IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II	Padova	Veneto
Italy	Azienda Unità Sanitaria Locale di Reggio Emilia/IRCCS	Reggio Emilia	Emilia-Romagna
Italy	Ospedale Infermi AUSL della Romagna; U.O Operativa di Oncologia	Rimini	Emilia-Romagna
Italy	Policlinico Universitario Agostino Gemelli	Roma	Lazio
Italy	Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia	Rozzano	Lombardia
Italy	Azienda ULSS 8 Berica; Oncologia Medica - Ospedlae di Vicenza	Vicenza	Veneto
Jordan	King Hussein Cancer Center	Amman
Kenya	International Cancer Institute (ICI)	Eldoret
Kenya	Aga Khan University Hospital	Nairobi
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul St Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Lebanon	Rizk Hospital	Beirut
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	Centro Estatal de Cancerologia de Chihuahua; ONCOLOGY	Chihuahua
Mexico	Iem-Fucam	D.f.	Mexico CITY (federal District)
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara	Jalisco
Mexico	Investigacion Oncofarmaceutica	La Paz	BAJA California SUR
Mexico	Filios Alta Medicina	Monterrey	Nuevo LEON
Mexico	Hospital Universitario; Dr. Jose E. Gonzalez	Monterrey	Nuevo LEON
Mexico	Hospital Zambrano Hellion TecSalud	Monterrey	Nuevo LEON
Mexico	Cuidados oncologicos	Querétaro	Queretaro
Mexico	Oncologico Potosino	San Luis Potosí	SAN LUIS Potosi
Oman	Sultan Qaboos Comprehensive Cancer Care & Research Center	Muscat
Poland	Szpital Morski im.PCK; Oddzial Onkologii Klinicznej, Oddzial Dzienny	Gdynia
Poland	Przychodnia Lekarska KOMED, Roman Karaszewski	Konin
Poland	Szpital Wojewódzki im. Miko?aja Kopernika; Oddzia? Dzienny Chemioterapii	Koszalin
Poland	Ars Medical Sp. z o. o.	Pi?a
Poland	Szpital Kliniczny im. H.Swiecickiego UM w Poznaniu	Pozna?
Poland	MRUKMED Lekarz Beata Madej-Mruk i Partner Spolka Partnerska Oddzial nr 1 w Rzeszowie	Rzeszow
Poland	Centrum Onkologii ? Instytut im. Marii Sk?odowskiej-Curie Klinika Nowotworów Piersi i Chirurgii	Warszawa
Portugal	IPO de Coimbra; Servico de Oncologia Medica	Coimbra
Portugal	Hospital da Luz; Departamento de Oncologia Medica	Lisboa
Portugal	Hospital de S. Francisco Xavier; Unidade de Oncologia Medica	Lisboa
Portugal	Hospital Beatriz Angelo; Departamento de Oncologia	Loures
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Spain	Hospital Clínic i Provincial; Servicio de Oncología	Barcelona
Spain	Hospital Universitario Clínico San Cecilio; Servicio de oncologia	Granada
Spain	Hospital Juan Ramon Jimenez;Servicio de Oncologia	Huelva
Spain	Hospital Universitario de Canarias;servicio de Oncologia	La Laguna	Tenerife
Spain	Centro Oncologico MD Anderson Internacional; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Sant Andreu de La Barca	Barcelona
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	LA Coruña
Spain	Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia	Valencia
Spain	Hospital Universitario Miguel Servet; Servicio Oncologia	Zaragoza
Taiwan	Changhua Christian Hospital; Dept of Surgery	Changhua
Taiwan	China Medical University Hospital; Surgery	Taichung
Taiwan	National Cheng Kung University Hospital; Oncology	Tainan
Taiwan	Taipei Veterans General Hospital Office of General Surgery	Taipei
Taiwan	National Taiwan University Hospital ; Dept of Surgery & Hepatitis Research Center	Taipei 100
Thailand	Rajavithi Hospital; Division of Medical Oncology	Bangkok
Thailand	Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital; Department of Surgery/Head Neck and Breast Unit; Clinical Trial	Chiang Mai
Thailand	Songklanagarind Hospital; Department of Oncology	Songkhla
Turkey	Adana Baskent University Hospital; Medical Oncology	Adana
Turkey	Ankara City Hospital; Oncology	Ankara
Turkey	Ankara Oncology Hospital; Oncology	Ankara
Turkey	Gazi Uni Medical Faculty Hospital; Oncology Dept	Ankara
Turkey	Uludag Uni Hospital; Oncology	Bursa
Turkey	Dicle University Faculty of Medicine	Diyarbakir
Turkey	Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi	Edirne
Turkey	Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department	Erzurum
Turkey	Medipol University Medical Faculty; Oncology Department	Istanbul
Turkey	Prof. Dr. Cemil Tascioglu City Hospital; Med Onc	Istanbul
Turkey	Ege Uni Medical Faculty; Oncology Dept	Izmir
Turkey	Katip Celebi University Ataturk Training and Research Hospital; Oncology	Izmir
Turkey	Kocaeli University Faculty of Medicine; Medical oncology	Izmit
Turkey	Erciyes Uni ; Medical Oncology	Kayseri
Turkey	Antalya Memorial Hastanesi; Onkoloji	Kepez
Turkey	Mersin City Education and Research Hospital	Mersin
Turkey	Ondokuz Mayis Univ. Med. Fac.	Samsun
Turkey	Ac?badem Maslak Hastanesi Büyükdere	Sar?yer/?stanbul
Turkey	Medical Park Seyhan Hospital; Oncology Department	Seyhan
Turkey	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye/Ankara
Turkey	Namik Kemal Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, 100	Tekirdag
Turkey	Karadeniz Tecnical University Medical Faculty; Oncology Department	Trabzon
Turkey	Ac?badem Altunizade Hastanesi; Oncology	Üsküdar
Uganda	Uganda Cancer Institute; Fred Hutchinson Cancer Research Center	Kampala
United Arab Emirates	Burjeel Medical City-Abu Dhabi	Abu Dhabi
United Arab Emirates	Tawam Hospital; Medical Oncology Department	Al Ain
United Kingdom	Ysbyty Gwynedd Hospital	Bangor
United Kingdom	Royal United Hospital; Oncology Department	Bath
United Kingdom	Blackpool Victoria Hospital	Blackpool
United Kingdom	University Hospital North Tees	Cleveland
United Kingdom	Royal Cornwall Hospital; Dept of Clinical Oncology	Cornwall
United Kingdom	Charing Cross Hospital; Medical Oncology.	London
United Kingdom	Maidstone Hospital; Kent Oncology Centre	Maidstone
United Kingdom	Nottingham University Hospitals NHS Trust - City Hospital	Nottingham
United Kingdom	Royal Preston Hosp; Rosemere Cancer Ctr	Preston
United Kingdom	North Wales Cancer Treatment Centre, Glan Clwyd Hospital	Rhyl
United Kingdom	Queen's Hospital; Oncology	Romford
United Kingdom	Singleton Hospital; Cancer Institute	Swansea
United States	Maryland Oncology Hematology - Annapolis	Annapolis	Maryland
United States	Texas Oncology - Austin	Austin	Texas
United States	Swedish Cancer Institute	Cary	North Carolina
United States	Texas Oncology - DFW	Dallas	Texas
United States	Swedish Cancer Institute - Edmonds Campus	Edmonds	Washington
United States	Texas Oncology - El Paso	El Paso	Texas
United States	West Cancer Center	Germantown	Tennessee
United States	St Mary's Hospital and Medical Center	Grand Junction	Colorado
United States	Genesis Cancer Center	Hot Springs	Arkansas
United States	Swedish Cancer Institute - Issaquah	Issaquah	Washington
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	Los Angeles Hematology Oncology Medical Group	Los Angeles	California
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Hightower Clinical	Oklahoma City	Oklahoma
United States	Florida Cancer Specialists - EAST - SCRI - PPDS	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  China,  Colombia,  France,  Germany,  Hungary,  India,  Italy,  Jordan,  Kenya,  Korea, Republic of,  Lebanon,  Mexico,  Oman,  Poland,  Portugal,  Spain,  Taiwan,  Thailand,  Turkey,  Uganda,  United Arab Emirates,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1		From randomization for maintenance therapy to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 50 months)
Secondary	Overall Survival		From randomization for maintenance therapy to death from any cause (up to 122 months)
Secondary	Objective Response Rate, as Determined by the Investigator According to RECIST v1.1	The objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart.	From randomization for maintenance therapy to disease progression or death (up to 50 months)
Secondary	Duration of Response, as Determined by the Investigator According to RECIST v1.1		From first occurrence of documented objective response after randomization for maintenance therapy to disease progression or death from any cause, whichever occurs first (up to 50 months)
Secondary	Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1	The clinical benefit rate is defined as the percentage of participants with stable disease for =24 weeks or a complete response (CR) or partial response (PR).	From randomization for maintenance therapy to disease progression or death (up to 50 months)
Secondary	Mean Role Functioning Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire		Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 10 years)
Secondary	Mean Change from Baseline in the Role Functioning Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire		Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 10 years)
Secondary	Mean Physical Functioning Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire		Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 10 years)
Secondary	Mean Change from Baseline in the Physical Functioning Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire		Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 10 years)
Secondary	Mean Global Health Status/Quality of Life Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire		Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 10 years)
Secondary	Mean Change from Baseline in the Global Health Status/Quality of Life Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire		Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 10 years)
Secondary	Number of Participants with at Least One Adverse Event, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI CTCAE v5.0)		From Baseline until 28 days after the final dose of study treatment (up to 10 years, 3 months)
Secondary	Number of Participants with Abnormalities in Clinical Laboratory Test Results		From Baseline until 28 days after the final dose of study treatment (up to 10 years, 3 months)