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Search / Trial NCT06065748

A Study to Evaluate Efficacy and Safety of Giredestrant Compared With Fulvestrant (Plus a CDK4/6 Inhibitor), in Participants With ER-Positive, HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer)

Launched by HOFFMANN-LA ROCHE · Sep 26, 2023

Trial Information

Current as of July 28, 2025

Recruiting

Keywords

Oral Selective Estrogen Receptor Degrader (Serd) Cdk4/6 Inhibitor (Cdk4/6i) Esr1 Mutation

ClinConnect Summary

This clinical trial, called the pionERA study, is researching two different medications, giredestrant and fulvestrant, both used with a type of drug called a CDK4/6 inhibitor, to see which one works better for treating advanced breast cancer that is estrogen receptor-positive (ER+) and HER2-negative. This study is specifically for patients who have already received some hormone treatments but their cancer did not respond well. The trial aims to find out how effective and safe these treatments are.

To be eligible for this trial, participants must have advanced breast cancer that is not curable, with a confirmed ER+ and HER2- status from a recent biopsy. They should also have a specific mutation in their tumor's DNA and must have shown resistance to earlier hormone treatments. People aged 65 to 74, regardless of gender, can participate, and those who are premenopausal will need to agree to receive additional hormone therapy during the trial. Participants can expect regular check-ups and monitoring while receiving one of the study medications, contributing to important research that may help improve treatment options for others in the future.

Gender

ALL

Eligibility criteria

  • Inclusion Criteria:
  • Locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
  • Documented estrogen receptor-positive (ER+), HER2-negative (HER2-) tumor assessed locally on the most recent tumor biopsy (or an archived tumor sample if a recent tumor sample is not available for testing)
  • Confirmed ESR1 mutation status (ESR1m versus ESR1nmd) in baseline circulating tumor DNA (ctDNA) through central laboratory testing
  • Resistance to prior adjuvant endocrine therapy (ET), which is defined as having relapsed with prior standard adjuvant ET, on-treatment after \>/=12 months or off-treatment within 12 months of completion. Prior use of adjuvant CDK4/6i is allowed (if relapse occurred \>/=12 months since completion).
  • No prior systemic anti-cancer therapy for advanced disease
  • Measurable disease as defined per RECIST v.1.1 or non-measurable (including bone-only) disease
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1
  • For pre/perimenopausal women and for men: willing to undergo and maintain treatment with approved LHRH agonist therapy (as per local guidelines) for the duration of study treatment
  • Exclusion Criteria:
  • Prior systemic therapy (e.g., prior chemotherapy, immunotherapy, or biologic therapy) for locally advanced unresectable or metastatic breast cancer
  • Prior treatment with another SERD (e.g., fulvestrant, oral SERDs) or novel ER-targeting agents
  • Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
  • Active cardiac disease or history of cardiac dysfunction
  • Clinically significant history of liver disease

About Hoffmann La Roche

Hoffmann-La Roche, commonly known as Roche, is a global leader in biotechnology and pharmaceuticals, committed to advancing healthcare through innovative research and development. With a strong focus on oncology, immunology, infectious diseases, and central nervous system disorders, Roche leverages cutting-edge science to deliver transformative therapies and diagnostics. The company is dedicated to improving patient outcomes by conducting rigorous clinical trials and collaborating with healthcare professionals and organizations worldwide. Roche's unwavering commitment to precision medicine and personalized healthcare positions it at the forefront of the industry, driving progress in the quest for effective treatments and improved patient care.

Locations

Charleston, South Carolina, United States

Lyon, , France

Sioux Falls, South Dakota, United States

Avignon, , France

Lille, , France

Detroit, Michigan, United States

Edmonton, Alberta, Canada

Oshawa, Ontario, Canada

Regina, Saskatchewan, Canada

Lima, , Peru

Rennes, , France

Toronto, Ontario, Canada

Hong Kong, , Hong Kong

Boston, Massachusetts, United States

Washington, District Of Columbia, United States

Park Ridge, Illinois, United States

Gent, , Belgium

Huelva, , Spain

Christchurch, , New Zealand

Tacoma, Washington, United States

Greenbrae, California, United States

Bruxelles, , Belgium

Leuven, , Belgium

Jau, Sp, Brazil

Mississauga, Ontario, Canada

Hangzhou, , China

Shanghai City, , China

Freiburg, , Germany

Patras, , Greece

Jerusalem, , Israel

Palmerston North, , New Zealand

Szczecin, , Poland

Porto, , Portugal

Singapore, , Singapore

Jaen, , Spain

Valencia, , Spain

Taipei City, , Taiwan

Austin, Texas, United States

Porto Alegre, Rs, Brazil

Caen, , France

Innsbruck, , Austria

Los Angeles, California, United States

Taichung, , Taiwan

Reims Cedex, , France

Lyon, , France

Lexington, Kentucky, United States

Geelong, Victoria, Australia

Warrnambool, Victoria, Australia

Atlanta, Georgia, United States

Erlangen, , Germany

Kingswood, New South Wales, Australia

Thunder Bay, Ontario, Canada

Villejuif, , France

Cincinnati, Ohio, United States

Singapore, , Singapore

Clermont Ferrand, , France

Green Bay, Wisconsin, United States

Sevilla, , Spain

Fairfax, Virginia, United States

Sevilla, , Spain

Valencia, , Spain

Bangkok, , Thailand

Porto Alegre, Rs, Brazil

Louisville, Kentucky, United States

Bangkok, , Thailand

Shanghai, , China

Harbor City, California, United States

Barrie, Ontario, Canada

Springfield, Illinois, United States

Seongnam Si, , Korea, Republic Of

Trois Rivieres, Quebec, Canada

Pune, Maharashtra, India

Seoul, , Korea, Republic Of

Seoul, , Korea, Republic Of

Seoul, , Korea, Republic Of

Bangkok, , Thailand

Besancon, , France

New Delhi, Delhi, India

Tianjin, Tianjin, China

Tampere, , Finland

Beijing, , China

Hong Kong, , Hong Kong

Auburn, California, United States

Seongnam Si, , Korea, Republic Of

Seoul, , Korea, Republic Of

Trivandrum, Kerala, India

Jau, Sp, Brazil

Milano, Lombardia, Italy

Taipei, , Taiwan

Taipei, , Taiwan

Bangkok, , Thailand

Altamonte Springs, Florida, United States

Seoul, , Korea, Republic Of

Washington, District Of Columbia, United States

Heidelberg, , Germany

Koeln, , Germany

Guatemala City, , Guatemala

Hong Kong, , Hong Kong

Macerata, Marche, Italy

Madrid, , Spain

Songkhla, , Thailand

Cordoba, , Argentina

Budapest, , Hungary

Liège, , Belgium

Barretos, Sp, Brazil

Denver, Colorado, United States

Dallas, Texas, United States

Lublin, , Poland

Scarborough, Maine, United States

Saskatoon, Saskatchewan, Canada

Harbin, , China

Caen, , France

Muenchen, , Germany

Aviano (Pn), Friuli Venezia Giulia, Italy

Lisboa, , Portugal

Jerez De La Frontera, Cadiz, Spain

Sevilla, , Spain

Essen, , Germany

La Rioja, , Argentina

Besancon, , France

Homburg/Saar, , Germany

Lima, , Peru

Songkhla, , Thailand

Porto Alegre, Rio Grande Do Sul, Brazil

Coimbra, , Portugal

Lima, , Peru

Sao Paulo, , Brazil

Lima, , Peru

Namur, , Belgium

Lille, , France

Reims Cedex, , France

Erlangen, , Germany

Udine, Friuli Venezia Giulia, Italy

Wien, , Austria

Graz, , Austria

Ulsan, , Korea, Republic Of

Rosario, , Argentina

Sao Paulo, Sp, Brazil

Budapest, , Hungary

Huelva, , Spain

Sevilla, , Spain

Jacksonville, Florida, United States

Napoli, Campania, Italy

Seoul, , Korea, Republic Of

Wilrijk, , Belgium

Athens, , Greece

Linz, , Austria

Ljubljana, , Slovenia

Madrid, , Spain

St Albans, Victoria, Australia

Angers, , France

Lisboa, , Portugal

Hong Kong, , Hong Kong

Lima, , Peru

Santiago, , Chile

Germantown, Tennessee, United States

Littleton, Colorado, United States

Rosario, , Argentina

Fuzhou City, , China

Rozzano, Lombardia, Italy

Jinan, , China

Zhengzhou, , China

Jau, São Paulo, Brazil

Morgantown, West Virginia, United States

Chengdu, , China

Wuhan, , China

Monteria, , Colombia

Deggendorf, , Germany

Homburg/Saar, , Germany

Mönchengladbach, , Germany

Brescia, Lombardia, Italy

Trujillo, , Peru

Warszawa, , Poland

Valencia, , Spain

Iasi, , Romania

Nanning, , China

Thessaloniki, , Greece

Roma, Lazio, Italy

La Rochelle, , France

Buenos Aires, , Argentina

Porto Alegre, Rs, Brazil

Arequipa, , Peru

Pozuelo De Alarcon, Madrid, Spain

Taichung, , Taiwan

Athens, , Greece

Xuzhou, Jiangsu, China

Goiania, Go, Brazil

Port Elizabeth, , South Africa

Sao Paulo, Sp, Brazil

Rennes, , France

Zhejiang, , China

Chongqing, , China

Daegu, , Korea, Republic Of

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Bologna, Emilia Romagna, Italy

Padova, Veneto, Italy

Parma, Emilia Romagna, Italy

Urumqi, , China

Porto Alegre, Rio Grande Do Sul, Brazil

Rozzano, Lombardia, Italy

Seoul, , Korea, Republic Of

Misterbianco (Ct), Sicilia, Italy

Florence, Toscana, Italy

Milwaukee, Wisconsin, United States

San José, , Costa Rica

Steyr, , Austria

Ramat Gan, , Israel

Daphne, Alabama, United States

Gdynia, , Poland

Petah Tikva, , Israel

Jamaica, New York, United States

Changchun City, , China

Trujillo, , Peru

Konin, , Poland

Novara, Piemonte, Italy

Avellino, Campania, Italy

Sippy Downs, Queensland, Australia

Vitoria, Es, Brazil

San José, , Costa Rica

Providence, Rhode Island, United States

Palmerston North, , New Zealand

Craiova, , Romania

Taipei, , Taiwan

El Palmar, Murcia, Spain

Wuhan City, , China

Roma, Lazio, Italy

Kansas City, Missouri, United States

Sacramento, California, United States

Heidelberg, , Germany

Changsha City, , China

Barcelona, , Spain

Mechelen, , Belgium

Frenchs Forest, New South Wales, Australia

Guangzhou City, , China

South Brisbane, Queensland, Australia

Bergamo, Lombardia, Italy

Tel Aviv, , Israel

Jinan City, , China

Frederick, Maryland, United States

Sao Paulo, Sp, Brazil

Meldola, Emilia Romagna, Italy

Saint Petersburg, Florida, United States

Xi'an City, , China

Brescia, Lombardia, Italy

Bucuresti, , Romania

Cape Town, , South Africa

Guatemala, , Guatemala

Szczecin, , Poland

Toulouse, , France

Recife, Pe, Brazil

Taiyuan City, , China

Lancaster, Pennsylvania, United States

Rio De Janeiro, Rj, Brazil

Atlanta, Georgia, United States

Samsun, , Turkey

Vigo, Pontevedra, Spain

Innsbruck, , Austria

Ijui, Rs, Brazil

Porto Alegre, Rs, Brazil

Oaxaca De Juárez, Oaxaca, Mexico

Mexico City, , Mexico

Bamberg, , Germany

Tallahassee, Florida, United States

East Brunswick, New Jersey, United States

Santiago, , Chile

Ciudad De Guatemala, , Guatemala

Gdynia, , Poland

Ankara, , Turkey

Timisoara, , Romania

San Juan, , Puerto Rico

Linz, , Austria

York, Pennsylvania, United States

Pune, Maharashtra, India

Lak Si, , Thailand

La Rochelle, , France

Adelaide, South Australia, Australia

Brindisi, Puglia, Italy

Lisboa, , Portugal

Monterrey, Nuevo Leon, Mexico

Taizhou, , China

Kuopio, , Finland

Rosario, , Argentina

Kingswood, New South Wales, Australia

Vigo, Pontevedra, Spain

Porto Alegre, Rio Grande Do Sul, Brazil

Barcelona, , Spain

Levis, Quebec, Canada

Luoyang, , China

Chicoutimi, Quebec, Canada

Xitun Dist., , Taiwan

West Palm Beach, Florida, United States

Bakirkoy / Istanbul, , Turkey

Taizhou, , China

Philadelphia, Pennsylvania, United States

Düsseldorf, , Germany

Guadalajara, Jalisco, Mexico

Queréaro, Queretaro, Mexico

Santiago, , Chile

Athina, , Greece

Ciudad De Guatemala, , Guatemala

Salcajá, , Guatemala

Hsinchu City, , Taiwan

Annapolis, Maryland, United States

Medford, Oregon, United States

Ciudad Autonoma Buenos Aires, , Argentina

Bensalem, Pennsylvania, United States

Richmond, Virginia, United States

Valledupar, , Colombia

Recoleta, , Argentina

Lima, , Peru

Mersin, , Turkey

Adelaide, South Australia, Australia

Fortaleza, Ce, Brazil

Petah Tikva, , Israel

North Sydney, New South Wales, Australia

Kozhikode, Kerala, India

Jacksonville, Florida, United States

Cerritos, California, United States

Badalona, Barcelona, Spain

Bydgoszcz, , Poland

Gliwice, , Poland

Koszalin, , Poland

Kielce, , Poland

Taipei City, , Taiwan

Fuzhou City, , China

?ód?, , Poland

Pretoria, , South Africa

Wuhan City, , China

Lima, , Peru

Bogota, D.C., , Colombia

Singapore, , Singapore

Sant Andreu De La Barca, Barcelona, Spain

Banglore, Karnataka, India

Kecskemét, , Hungary

Mexico City, , Mexico

Mexico City, Mexico City (Federal District), Mexico

Singapore, , Singapore

Newport Beach, California, United States

Montreal, Quebec, Canada

Tianjin, , China

Thessaloniki, , Greece

Chengdu City, , China

Nairobi, , Kenya

Luoyang City, , China

Miskolc, , Hungary

Xian, Shaanxi, China

Quebec City, Quebec, Canada

Nashville, Tennessee, United States

San José, , Costa Rica

Seoul, , Korea, Republic Of

Mumbai, Maharashtra, India

Rio De Janeiro, , Brazil

Nanning City, , China

Porto Alegre, Rs, Brazil

Aberdeen, South Dakota, United States

Puerto Montt, , Chile

Buenos Aires, , Argentina

Saint Jerome, Quebec, Canada

Ciudad De Guatemala, , Guatemala

Quetzaltenango, , Guatemala

Vila Nova De Gaia, , Portugal

Changchun City, , China

Guadalajara, Jalisco, Mexico

San Juan, , Argentina

Salvador, Ba, Brazil

Santiago, , Chile

Kunming City, , China

San José, , Costa Rica

Torrance, California, United States

San Juan, , Argentina

Montpellier, , France

Salgótarján, , Hungary

Muang Chiang Mai Delivery Branch 3, , Thailand

Kecskemét, , Hungary

Des Moines, Iowa, United States

Lima, , Peru

Lima, , Peru

Siedlce, , Poland

Sao Luis, , Brazil

Lublin, , Poland

Lexington, Kentucky, United States

Fort Myers, Florida, United States

Sao Luis, Ma, Brazil

Cali, , Colombia

Szczecin, , Poland

Singapore, , Singapore

Tampa, Florida, United States

Ciudad De Guatemala, , Guatemala

Santiago De Querétaro, Queretaro, Mexico

Bangkok, , Thailand

Fort Worth, Texas, United States

Thunder Bay, Ontario, Canada

Ciudad De México, Mexico City (Federal District), Mexico

Whangarei, , New Zealand

Providencia, , Chile

Sao Paulo, São Paulo, Brazil

Mexico City, , Mexico

Lima, , Peru

Coimbra, , Portugal

Porto, , Portugal

Macerata, Marche, Italy

Bydgoszcz, , Poland

Vila Nova De Gaia, , Portugal

Jaen, , Spain

Madrid, , Spain

Goiania, Goiás, Brazil

Recife, Pernambuco, Brazil

Athens, , Greece

Misterbianco (Ct), Sicilia, Italy

Padova, Veneto, Italy

Warszawa, , Poland

Pozuelo De Alarcon, Madrid, Spain

Madrid, , Spain

Taipei, , Taiwan

Izmir, , Turkey

Banglore, Karnataka, India

Sihhiye/Ankara, , Turkey

Barretos, São Paulo, Brazil

Milano, Lombardia, Italy

Ciudad Autonoma Buenos Aires, , Argentina

Fortaleza, Ceará, Brazil

Sao Paulo, São Paulo, Brazil

Meldola, Emilia Romagna, Italy

Gliwice, , Poland

Koszalin, , Poland

Muenchen, , Germany

Aviano (Pn), Friuli Venezia Giulia, Italy

Kielce, , Poland

Jerez De La Frontera, Cadiz, Spain

Sao Paulo, São Paulo, Brazil

Vitoria, Espírito Santo, Brazil

Newport Beach, California, United States

Ijui, Rio Grande Do Sul, Brazil

Porto Alegre, Rio Grande Do Sul, Brazil

Larissa, , Greece

Cluj County, , Romania

Frederick, Maryland, United States

Bologna, Emilia Romagna, Italy

?ód?, , Poland

Koeln, , Germany

Roma, Lazio, Italy

Kadiköy, , Turkey

Jerusalem, , Israel

Miskolc, , Hungary

Lisboa, , Portugal

Tel Aviv, , Israel

Sant Andreu De La Barca, Barcelona, Spain

Pennington, New Jersey, United States

Raleigh, North Carolina, United States

Irving, Texas, United States

Buenos Aires, , Argentina

Ciudad Autonoma Buenos Aires, , Argentina

North Sydney, New South Wales, Australia

Salvador, Bahia, Brazil

Brasilia, Distrito Federal, Brazil

Sao Luis, Maranhão, Brazil

Montreal, Quebec, Canada

Providencia, , Chile

Guangzhou City, , China

Kuopio, , Finland

Deggendorf, , Germany

Ciudad De Guatemala, , Guatemala

Salgótarján, , Hungary

Udine, Friuli Venezia Giulia, Italy

Brindisi, Puglia, Italy

Whangarei, , New Zealand

Siedlce, , Poland

Cluj Napoca, , Romania

El Palmar (El Palmar), Murcia, Spain

Lak Si, , Thailand

Muang Chiang Mai Delivery Branch 3, , Thailand

Christchurch, , New Zealand

Charleroi, , Belgium

Glendale, California, United States

Providence, Rhode Island, United States

Thane, Maharashtra, India

O'fallon, Missouri, United States

Omaha, Nebraska, United States

Roseville, California, United States

Guatemala, , Guatemala

Adapazar?, , Turkey

Jau, , Brazil

Barretos, , Brazil

Sao Paulo, , Brazil

Goiania, , Brazil

Sao Paulo, , Brazil

Vitoria, , Brazil

Fortaleza, , Brazil

Mexico City, , Mexico

Ciudad De México, , Mexico

Liège, , Belgium

Trujillo, , Peru

Wilrijk, , Belgium

Concepción, , Chile

Arequipa, , Peru

Patients applied

0 patients applied

Trial Officials

Clinical Trials

Study Director

Hoffmann-La Roche

Timeline

First submit

Trial launched

Trial updated

Estimated completion

Not reported