Triple Negative Breast Neoplasms Clinical Trial
Official title:
An Open-label, Randomized, Phase 2/3 Study of Olaparib Plus Pembrolizumab Versus Chemotherapy Plus Pembrolizumab After Induction of Clinical Benefit With First-line Chemotherapy Plus Pembrolizumab in Participants With Locally Recurrent Inoperable or Metastatic Triple Negative Breast Cancer (TNBC) (KEYLYNK-009)
| Verified date | May 2024 |
| Source | Merck Sharp & Dohme LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of this study is to compare the efficacy of olaparib (MK-7339) plus pembrolizumab (MK-3475) with chemotherapy plus pembrolizumab after induction with first-line chemotherapy plus pembrolizumab in triple negative breast cancer (TNBC). The primary hypotheses are: 1. Olaparib plus pembrolizumab is superior to chemotherapy plus pembrolizumab with respect to progression-free survival (PFS). 2. Olaparib plus pembrolizumab is superior to chemotherapy plus pembrolizumab with respect to overall survival (OS). As of Amendment 3, study enrollment was discontinued. Participants who were receiving benefit from the study intervention could continue treatment until criteria for discontinuation are met. Participants who are on study treatment or in follow-up phase will no longer have tumor response assessments by BICR.
| Status | Active, not recruiting |
| Enrollment | 462 |
| Est. completion date | November 18, 2025 |
| Est. primary completion date | December 15, 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: Induction Period: - Has locally recurrent inoperable TNBC that has not previously been treated with chemotherapy and that cannot be treated with curative intent OR has metastatic TNBC that has not been previously treated with chemotherapy - Has been treated with anthracycline and/or a taxane in the neoadjuvant/adjuvant setting, if they received systemic treatment in the neoadjuvant/adjuvant setting, unless anthracycline and/or taxane was contraindicated or not considered the best treatment option for the participant in the opinion of the treating physician - Has measurable disease based on RECIST 1.1 - Has provided a recently obtained or archival (no more than 3 years old) core or excisional biopsy of a tumor lesion not previously irradiated - Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 as assessed within 7 days prior to the start of induction study treatment - Has a life expectancy =27 weeks from the day of first study treatment - Demonstrate adequate organ function within 10 days prior to the start of study treatment - A male participant must agree to be abstinent or use contraception and refrain from donating sperm during the intervention period and for at least the time needed to eliminate each study intervention (95 days for olaparib and chemotherapy; no requirement for pembrolizumab) - A female participant must not be pregnant or breastfeeding and must agree to the following if is a woman of childbearing potential (WOCBP): have a negative pregnancy test within 24 hours before the start of study treatment and agree to be abstinent or use contraception and refrain from donating eggs (ova, oocytes) during the intervention period and for at least the time needed to eliminate each study intervention (180 days for olaparib and chemotherapy; 120 days for pembrolizumab) Post-induction Period: - Has received up to 6 cycles but not less than 4 cycles of induction therapy without permanently discontinuing from pembrolizumab or both carboplatin and gemcitabine - Has achieved complete response (CR), partial response (PR), or stable disease (SD) based on RECIST 1.1 by Blinded Independent Central Review (BICR) at the Week 18 evaluation - Is able to complete during post-induction at least the Cycle 1, Day 1 doses of olaparib and pembrolizumab or the Cycle 1, Day 1 doses of at least one of the chemotherapy agents being administered at the end of induction (carboplatin and/or gemcitabine) in addition to pembrolizumab - Has ECOG performance status of 0 or 1, as assessed within 7 days prior to the start of post-induction study treatment - Has no higher than Grade 1 toxicities related to induction therapy (excluding alopecia) prior to randomization Exclusion Criteria: Induction Period: - Has a known additional malignancy that is progressing or has required active treatment within the past 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, cervical cancer in situ) that have undergone potentially curative therapy - Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment - Has an active autoimmune disease that has required systemic treatment in the past 2 years - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis - Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML - Has a history of (non-infectious) pneumonitis\interstitial lung disease that required steroids or current pneumonitis\interstitial lung disease - Has active, or a history of, interstitial lung disease - Has a known history of active tuberculosis - Has an active infection requiring systemic therapy - Has a known history of human immunodeficiency virus (HIV) infection - Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection - Has a history of class II-IV congestive heart failure or myocardial infarction within 6 months of first study treatment - Has neuropathy =Grade 2 - Has not recovered (eg, to =Grade 1 or to baseline) from AEs due to a previously administered therapy - Has a known history of hypersensitivity or allergy to pembrolizumab, olaparib and any of its components, and/or to any of the study chemotherapies (eg, carboplatin or gemcitabine) and any of their components - Has severe hypersensitivity (=Grade 3) to the study treatments and/or any of their excipients - Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study - Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the Screening Visit through 180 days after the last dose of study treatment - Is a WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation - Has received prior therapy with either olaparib or any other poly adenosine diphosphate ribose polymerase (PARP) inhibitor - Has received prior radiotherapy within 2 weeks of start of study treatment - Has received colony-stimulating factors (eg, granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony stimulating factor [GM-CSF] or recombinant erythropoietin) within 2 weeks prior to the first dose of study treatment - Has had an allogenic tissue/solid organ transplant. - Has received previous allogenic bone marrow transplant or double umbilical cord transplantation (dUCBT) - Has had major surgery within 2 weeks of starting study treatment or has not recovered from any effects of any major surgery - Has received a live or live-attenuated vaccine within 30 days prior to first study treatment - Is receiving any medication prohibited in combination with study chemotherapies unless medication was stopped within 7 days prior to first study treatment - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T cell receptor (such as cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137) or has previously participated in a study evaluating pembrolizumab regardless of treatment received - Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment - Has presence of uncontrolled, potentially reversible cardiac conditions, as judged by the investigator - Has a history or current evidence of any condition (eg, cytopenia, transfusion-dependent anemia, or thrombocytopenia), therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's involvement for the full duration of the study, or is not in the best interest of the participant to be involved, in the opinion of the treating investigator - Is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption) - Is unlikely to comply with the study procedures, restrictions, and requirements of the study; as judged by the investigator Post-induction Period: - Has severe hypersensitivity (=Grade 3) to the study treatments and/or any of their excipients - Has permanently discontinued from both carboplatin and gemcitabine during induction due to toxicity - Has permanently discontinued from pembrolizumab during induction due to toxicity - Has received less than 4 cycles of chemotherapy plus pembrolizumab during induction - Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study - Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study |
| Country | Name | City | State |
|---|---|---|---|
| Canada | CSSS de Laval- Hopital de la Cite de la Sante ( Site 0011) | Laval | Quebec |
| Canada | Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0003) | Montreal | Quebec |
| Canada | Jewish General Hospital ( Site 0010) | Montreal | Quebec |
| Canada | McGill University Health Centre ( Site 0002) | Montreal | Quebec |
| Canada | Princess Margaret Cancer Centre ( Site 0005) | Toronto | Ontario |
| Chile | IC La Serena Research ( Site 0511) | La Serena | Coquimbo |
| Chile | Fundacion Arturo Lopez Perez ( Site 0500) | Santiago | Region M. De Santiago |
| Chile | Pontificia Universidad Catolica de Chile ( Site 0501) | Santiago | Region M. De Santiago |
| Chile | Centro Investigación del Cáncer James Lind ( Site 0510) | Temuco | Araucania |
| Chile | Oncocentro ( Site 0502) | Vina del Mar | Valparaiso |
| Colombia | Clinica de la Costa Ltda. ( Site 0600) | Barranquilla | Atlantico |
| Colombia | Organizacion Clinica Bonnadona-Prevenir S.A.S. ( Site 0609) | Barranquilla | Atlantico |
| Colombia | Fundacion Valle del Lili ( Site 0602) | Cali | Valle Del Cauca |
| Colombia | Hemato Oncologos S.A. ( Site 0603) | Cali | Valle Del Cauca |
| Colombia | Fundacion Colombiana de Cancerologia Clinica Vida ( Site 0601) | Medellin | Antioquia |
| Colombia | Oncomedica S.A. ( Site 0606) | Monteria | Cordoba |
| France | CHU Amiens Hopital Sud ( Site 1023) | Amiens | Somme |
| France | Institut Sainte Catherine ( Site 1026) | Avignon | Vaucluse |
| France | CHU-Jean Minjoz ( Site 1013) | Besancon | Doubs |
| France | Centre Francois Baclesse ( Site 1012) | Caen | Calvados |
| France | Centre Jean Perrin ( Site 1003) | Clermont-Ferrand Cedex 01 | Puy-de-Dome |
| France | Centre Leon Berard ( Site 1018) | Lyon | Rhone |
| France | CHR-METZ-THIONVILLE - Hopital de Mercy ( Site 1007) | Metz | Moselle |
| France | Centre de Cancerologie du Grand Montpellier ( Site 1009) | Montpellier | Languedoc-Roussillon |
| France | Hôpital Saint-Louis ( Site 1025) | Paris | |
| France | Centre Henri Becquerel ( Site 1020) | Rouen | Seine-Maritime |
| France | Institut Claudius Regaud IUCT Oncopole ( Site 1001) | Toulouse | Haute-Garonne |
| France | Institut Gustave Roussy ( Site 1010) | Villejuif | Val-de-Marne |
| Germany | Hochwaldkrankenhaus Bad Nauheim ( Site 1211) | Bad Nauheim | Hessen |
| Germany | Gynaekologisches Zentrum-Schwerpunkt Gyn. Onkologie ( Site 1205) | Bonn | Nordrhein-Westfalen |
| Germany | Universitaetsklinikum Carl Gustav Carus ( Site 1203) | Dresden | Sachsen |
| Germany | Universitaetsklinikum AoeR Duesseldorf ( Site 1210) | Duesseldorf | Nordrhein-Westfalen |
| Germany | Universitaetsklinikum Erlangen ( Site 1201) | Erlangen | Bayern |
| Germany | Kliniken Essen-Mitte ( Site 1215) | Essen | Nordrhein-Westfalen |
| Germany | Gynaekologisch-onkologische Praxis Hannover ( Site 1207) | Hannover | Niedersachsen |
| Germany | Universitaetsklinikum Mannheim GmbH ( Site 1213) | Mannheim | Baden-Wurttemberg |
| Germany | Klinik und Poliklinik fuer Frauenheilkunde und Geburtshilfe ( Site 1200) | Muenchen | Bayern |
| Germany | Sana Klinikum Offenbach Klinik fuer Gynakologie und Geburtshilfe ( Site 1206) | Offenbach am Main | Hessen |
| Germany | Frauenklinik St. Louise ( Site 1216) | Paderborn | Nordrhein-Westfalen |
| Hungary | Orszagos Onkologiai Intezet ( Site 1602) | Budapest | |
| Hungary | Debreceni Egyetem Klinikai Kozpont ( Site 1600) | Debrecen | |
| Hungary | Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 1604) | Kaposvar | |
| Hungary | Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 1608) | Kecskemét | Bacs-Kiskun |
| Hungary | Pecsi Tudomanyegyetem Klinikai Kozpont ( Site 1607) | Pecs | Baranya |
| Hungary | Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 1601) | Szolnok | Jasz-Nagykun-Szolnok |
| Hungary | Zala Megyei Szent Rafael Korhaz ( Site 1605) | Zalaegerszeg | Zala |
| Ireland | Cork University Hospital ( Site 0902) | Cork | |
| Ireland | St Vincents University Hospital ( Site 0900) | Dublin | |
| Japan | Fukushima Medical University Hospital ( Site 2201) | Fukushima | |
| Japan | Hiroshima City Hiroshima Citizens Hospital ( Site 2204) | Hiroshima | |
| Japan | Aichi Cancer Center Hospital ( Site 2202) | Nagoya | Aichi |
| Japan | Hyogo College of Medicine Hospital ( Site 2203) | Nishinomiya | Hyogo |
| Japan | National Hospital Organization - Osaka National Hospital - Institute For Clinical Research (Site 2200) | Osaka | |
| Korea, Republic of | Kyungpook National University Chilgok Hospital ( Site 2402) | Daegu | Taegu-Kwangyokshi |
| Korea, Republic of | National Cancer Center ( Site 2406) | Goyang-si | Kyonggi-do |
| Korea, Republic of | Gachon University Gil Medical Center ( Site 2408) | Incheon | |
| Korea, Republic of | Seoul National University Bundang Hospital ( Site 2409) | Seongnam-si | Kyonggi-do |
| Korea, Republic of | Asan Medical Center ( Site 2404) | Seoul | |
| Korea, Republic of | Samsung Medical Center ( Site 2405) | Seoul | |
| Korea, Republic of | Seoul National University Hospital ( Site 2403) | Seoul | |
| Korea, Republic of | Severance Hospital Yonsei University Health System ( Site 2401) | Seoul | |
| Korea, Republic of | Ajou University Hospital ( Site 2407) | Suwon-si | Kyonggi-do |
| Poland | Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 1913) | Gdynia | Pomorskie |
| Poland | Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 1912) | Gliwice | Slaskie |
| Poland | Pratia MCM Krakow ( Site 1919) | Krakow | Malopolskie |
| Poland | Pleszewskie Centrum Medyczne w Pleszewie Sp. z o.o. ( Site 1909) | Pleszew | Wielkopolskie |
| Poland | Regionalny Szpital Specjalistyczny Latawiec ( Site 1917) | Swidnica | Dolnoslaskie |
| Poland | Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (Site 1908) | Warszawa | Mazowieckie |
| Spain | Hospital Clinic I Provincial de Barcelona ( Site 0702) | Barcelona | |
| Spain | Hospital Universitari Vall d Hebron ( Site 0701) | Barcelona | |
| Spain | Instituto Oncologico Baselga.Hospital Quiron. ( Site 0707) | Barcelona | |
| Spain | Hospital Universitario Reina Sofia ( Site 0705) | Cordoba | Andalucia |
| Spain | Clinica Universitaria Navarra - Madrid ( Site 0700) | Madrid | |
| Spain | Hospital General Arnau de Vilanova de Valencia ( Site 0706) | Valencia | Valenciana, Comunitat |
| Taiwan | Kaohsiung Chang Gung Memorial Hospital ( Site 2304) | Kaohsiung | |
| Taiwan | National Cheng Kung University Hospital ( Site 2303) | Tainan | |
| Taiwan | China Medical University Hospital ( Site 2302) | Taipei | |
| Taiwan | Koo Foundation Sun Yat-Sen Cancer Center ( Site 2300) | Taipei | |
| Taiwan | MacKay Memorial Hospital ( Site 2301) | Taipei | |
| Ukraine | Chernihiv Medical Center of Modern Oncology ( Site 1520) | Chernihiv | Chernihivska Oblast |
| Ukraine | Dnipropetrovsk City Multidiscipline Clinical Hosp. 4 of DRC ( Site 1502) | Dnipro | Dnipropetrovska Oblast |
| Ukraine | MI Precarpathian Clinical Oncology Center ( Site 1506) | Ivano-Frankivsk | Ivano-Frankivska Oblast |
| Ukraine | Communal non profit enterprise Regional Clinical Oncology Center ( Site 1512) | Kharkiv | Kharkivska Oblast |
| Ukraine | Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 1508) | Kharkiv | Kharkivska Oblast |
| Ukraine | SI-Zaytsev institute of general and urgent surgery-NAMS ( Site 1518) | Kharkiv | Kharkivska Oblast |
| Ukraine | CI Krivorizhskiy oncology dispensery ( Site 1504) | Kryviy Rih | Dnipropetrovska Oblast |
| Ukraine | Medical Center Verum ( Site 1501) | Kyiv | |
| Ukraine | Medical Centre Consilium Medical ( Site 1514) | Kyiv | Kyivska Oblast |
| Ukraine | Medical center of the Limited Liability Company Yulis ( Site 1517) | Zaporizhzhia | Zaporizka Oblast |
| Ukraine | Medical Centre LLC Oncolife ( Site 1510) | Zaporizhzhya | Zaporizka Oblast |
| Ukraine | Zhytomyr Regional Oncology Center ( Site 1515) | Zhytomyr | Zhytomyrska Oblast |
| United Kingdom | Blackpool Victoria Hospital ( Site 0921) | Blackpool | Lancashire |
| United Kingdom | Raigmore Hospital ( Site 0915) | Inverness | Highland |
| United Kingdom | Barts Health NHS Trust ( Site 0912) | London | London, City Of |
| United Kingdom | North West Cancer Centre ( Site 0922) | Londonderry | London, City Of |
| United Kingdom | The Christie NHS Foundation Trust ( Site 0914) | Manchester | |
| United Kingdom | Musgrove Park Hospital ( Site 0918) | Taunton | Somerset |
| United States | Georgia Cancer Center at Augusta University ( Site 0129) | Augusta | Georgia |
| United States | Massachusetts General Hospital ( Site 0155) | Boston | Massachusetts |
| United States | University of Chicago ( Site 0159) | Chicago | Illinois |
| United States | Memorial Sloan-Kettering Cancer Center at Commack ( Site 0160) | Commack | New York |
| United States | Henry Ford Health System ( Site 0103) | Detroit | Michigan |
| United States | The Center For Cancer And Blood Disorders ( Site 0151) | Fort Worth | Texas |
| United States | University of Miami Sylvester CC ( Site 0146) | Miami | Florida |
| United States | Memorial Sloan Kettering Cancer Center- Monmouth ( Site 0161) | Middletown | New Jersey |
| United States | Virginia Piper Cancer Institute ( Site 0157) | Minneapolis | Minnesota |
| United States | Pacific Cancer Care ( Site 0142) | Monterey | California |
| United States | MSKCC-Bergen ( Site 0162) | Montvale | New Jersey |
| United States | Texas Oncology-New Braunfels ( Site 0168) | New Braunfels | Texas |
| United States | Memorial Sloan-Kettering Cancer Center ( Site 0156) | New York | New York |
| United States | Virginia Oncology Associates ( Site 0163) | Newport News | Virginia |
| United States | Virginia Oncology Associates ( Site 0153) | Norfolk | Virginia |
| United States | Mercy Clinic Oncology and Hematology ( Site 0110) | Oklahoma City | Oklahoma |
| United States | Texas Oncology - San Antonio Stone Oak ( Site 0166) | San Antonio | Texas |
| United States | Texas Oncology-San Antonio Medical Center ( Site 0158) | San Antonio | Texas |
| United States | Texas Oncology-San Antonio Northeast ( Site 0165) | San Antonio | Texas |
| United States | UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0138) | San Francisco | California |
| United States | John Wayne Cancer Institute ( Site 0111) | Santa Monica | California |
| United States | St. Joseph Heritage Healthcare ( Site 0104) | Santa Rosa | California |
| United States | Renovatio Clinical ( Site 0117) | The Woodlands | Texas |
| United States | Virginia Oncology Associates ( Site 0164) | Virginia Beach | Virginia |
| United States | YVMH dba Virginia Mason Memorial/North Star Lodge Cancer Center ( Site 0128) | Yakima | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Canada, Chile, Colombia, France, Germany, Hungary, Ireland, Japan, Korea, Republic of, Poland, Spain, Taiwan, Ukraine, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression-Free Survival (PFS) | PFS was defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR), or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as =20% increase in the sum of diameters (SOD) of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions was also considered PD. PFS is reported based on the product-limit (Kaplan-Meier) method for censored data. | Up to approximately 29 months | |
| Primary | Overall Survival (OS) | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS is reported based on the product-limit (Kaplan-Meier) method for censored data. | Up to approximately 29 months | |
| Secondary | Progression-Free Survival (PFS) in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Positive Tumors With a Combined Positive Score (CPS) =10 | PFS was defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR), or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as =20% increase in the sum of diameters (SOD) of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions was also considered PD. Only participants with a CPS =10 were included in this analysis. PFS is reported based on the product-limit (Kaplan-Meier) method for censored data. | Up to approximately 29 months | |
| Secondary | Overall Survival (OS) in Participants With PD-L1 Positive Tumors With a CPS =10 | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Only participants with a CPS =10 were included in this analysis. | Up to approximately 29 months | |
| Secondary | PFS in Participants With Breast Cancer Susceptibility Gene Mutation (BRCAm) Tumors | PFS was defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR), or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as =20% increase in the sum of diameters (SOD) of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions was also considered PD. Only participants with BRCAm-positive tumors were included in this analysis. PFS is reported based on the product-limit (Kaplan-Meier) method for censored data. | Up to approximately 29 months | |
| Secondary | OS in Participants With BRCAm Tumors | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Only participants with BRCAm-positive tumors were included in this analysis. | Up to approximately 29 months | |
| Secondary | Change From Baseline in Health-Related Quality-of-Life (QoL) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 29 and 30 Combined Score | EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the QoL question "How would you rate your overall quality of life during the past week?" (Item 30) were each scored on a 7-point scale (1=Very Poor to 7=Excellent), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Change from baseline in EORTC QLQ-C30 Items 29 and 30 combined scores was calculated based on a constrained longitudinal data analysis (cLDA) model with scores as response variable with covariates for treatment by time interaction, stratification factors (response at randomization (CR/PR vs. SD), baseline CPS for PD-L1 expression (PD-L1 CPS<1 vs. PD-L1 CPS=1) and BRCA status at randomization (BRCAm vs. BRCAwt)) as covariates. | Baseline and week 18 | |
| Secondary | Change From Baseline in Physical Functioning Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1- 5 Score | EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. The change from baseline in physical functioning (EORTC QLQ-C30 Items 1-5) score was calculated based on a cLDA model with scores as response variable with covariates for treatment by time interaction, stratification factors (response at randomization (CR/PR vs. SD), baseline CPS for PD-L1 expression (PD-L1 CPS<1 vs. PD-L1 CPS=1) and BRCA status at randomization (BRCAm vs. BRCAwt)) as covariates. | Baseline and week 18 | |
| Secondary | Change From Baseline in Emotional Functioning Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 21-24 Score | EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to 4 questions about their emotional functioning are scored on a 4-point scale (1=Not at All to 4=Very Much), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Change from baseline in emotional functioning (EORTC QLQ-C30 Items 21-24) score was calculated based on a cLDA model with scores as response variable with covariates for treatment by time interaction, stratification factors (response at randomization (CR/PR vs. SD), baseline CPS for PD-L1 expression (PD-L1 CPS<1 vs. PD-L1 CPS=1) and BRCA status at randomization (BRCAm vs. BRCAwt)) as covariates. | Baseline and week 18 | |
| Secondary | Change From Baseline in Systemic Therapy Side Effects Using the European Organization for Research and Treatment of Cancer Breast Cancer-Specific QoL Questionnaire (EORTC QLQ-BR23) Items 1-4, 6, 7, and 8 Score | EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30, consisting of functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects are scored on a 4-point scale (1=Not at All, 4=Very Much). Using linear transformation, raw scores are standardized, so scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score was calculated based on a cLDA model with scores as response variable with covariates for treatment by time interaction, stratification factors (response at randomization (CR/PR vs. SD), baseline CPS for PD-L1 expression (PD-L1 CPS<1 vs. PD-L1 CPS=1) and BRCA status at randomization (BRCAm vs. BRCAwt)) as covariates. | Baseline and week 18 | |
| Secondary | Change From Baseline in Visual Analogue Scale (VAS) Score on the European Quality of Life 5-dimension, 5-level Questionnaire (EQ-5D-5L) | The EQ-5D-5L is a questionnaire developed to assess health-related outcomes. The VAS is a component of the EQ-5D-5L that asks participants to rate their overall health on a vertical visual analogue scale, with the scale's ends labelled 'The best health you can imagine' (equivalent to a score of 0) and 'The worst health you can imagine' (equivalent to a score of 100). The change from baseline in VAS score was calculated based on a cLDA model with scores as response variable with covariates for treatment by time interaction, stratification factors (response at randomization (CR/PR vs. SD), baseline CPS for PD-L1 expression (PD-L1 CPS<1 vs. PD-L1 CPS=1) and BRCA status at randomization (BRCAm vs. BRCAwt)) as covariates. | Baseline and week 18 | |
| Secondary | Change From Baseline in Health-Related QoL Using the EORTC QLQ-C30 Items 29 and 30 Combined Score in Participants With Breast Cancer Susceptibility Gene Mutation (BRCAm) Tumors | EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the QoL question "How would you rate your overall quality of life during the past week?" (Item 30) were each scored on a 7-point scale (1=Very Poor to 7=Excellent), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. The change from baseline in EORTC QLQ-C30 Items 29 and 30 scores was calculated based on a constrained longitudinal data analysis (cLDA) model with scores as response variable with covariates for treatment by time interaction, stratification factors (response at randomization (CR/PR vs. SD), and baseline CPS for PD-L1 expression (PD-L1 CPS<1 vs. PD-L1 CPS=1)) as covariates. | Baseline and up to 18 weeks | |
| Secondary | Change From Baseline in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score in Participants With BRCAm Tumors | EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. The change from baseline in physical functioning (EORTC QLQ-C30 Items 1-5) score was calculated based on a constrained longitudinal data analysis (cLDA) model with scores as response variable with covariates for treatment by time interaction, stratification factors (response at randomization (CR/PR vs. SD), and baseline CPS for PD-L1 expression (PD-L1 CPS<1 vs. PD-L1 CPS=1)) as covariates. | Baseline and week 18 | |
| Secondary | Change From Baseline in Emotional Functioning Using the EORTC QLQ-C30 Items 21-24 Score in Participants With BRCAm Tumors | EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to 4 questions about their emotional functioning are scored on a 4-point scale (1=Not at All to 4=Very Much), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. The change from baseline in emotional functioning (EORTC QLQ-C30 Items 21-24) score was calculated based on a cLDA model with scores as response variable with covariates for treatment by time interaction, stratification factors (response at randomization (CR/PR vs. SD), and baseline CPS for PD-L1 expression (PD-L1 CPS<1 vs. PD-L1 CPS=1)) as covariates. | Baseline and week 18 | |
| Secondary | Change From Baseline in Systemic Therapy Side Effects Using the EORTC QLQ-BR23 Items 1-4, 6, 7, and 8 Score in Participants With BRCAm Tumors | EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30, consisting of functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects are scored on a 4-point scale (1=Not at All, 4=Very Much). Using linear transformation, raw scores are standardized, so scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score was calculated based on a cLDA model with scores as response variable with covariates for treatment by time interaction, stratification factors (response at randomization (CR/PR vs. SD), and baseline CPS for PD-L1 expression (PD-L1 CPS<1 vs. PD-L1 CPS=1)) as covariates. | Baseline and week 18 | |
| Secondary | Change From Baseline in Visual Analogue Scale (VAS) Score on the EQ-5D-5L in Participants With BRCAm Tumors | The EQ-5D-5L is a questionnaire developed to assess health-related outcomes. The VAS is a component of the EQ-5D-5L that asks participants to rate their overall health on a vertical visual analogue scale, with the scale's ends labelled 'The best health you can imagine' (equivalent to a score of 0) and 'The worst health you can imagine' (equivalent to a score of 100). The change from baseline in VAS score was calculated based on a cLDA model with scores as response variable with covariates for treatment by time interaction, stratification factors (response at randomization (CR/PR vs. SD), and baseline CPS for PD-L1 expression (PD-L1 CPS<1 vs. PD-L1 CPS=1)) as covariates. | Baseline and week 18 | |
| Secondary | Time to Deterioration (TTD) in Health-Related QoL Using the EORTC QLQ-C30 Items 29 and 30 Score | EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the QoL question "How would you rate your overall quality of life during the past week?" (Item 30) were each scored on a 7-point scale (1=Very Poor to 7=Excellent), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. TTD was defined as the time from baseline to the first onset of a =10-point decrease with confirmation by the subsequent visit of a =10-point decrease in Items 29 and 30 scale scores. TTD is reported based on the product-limit (Kaplan-Meier) method for censored data. | Baseline and up to approximately 29 months | |
| Secondary | TTD in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score | EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. TTD was defined as the time from baseline to the first onset of a =10-point decrease with confirmation by the subsequent visit of a =10-point decrease in physical functioning Items 1 to 5 scale scores. TTD is reported based on the product-limit (Kaplan-Meier) method for censored data. | Up to approximately 29 months | |
| Secondary | TTD in Emotional Functioning Using the EORTC QLQ-C30 Items 21-24 Score | EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to 4 questions about their emotional functioning are scored on a 4-point scale (1=Not at All to 4=Very Much), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. TTD was defined as the time from baseline to the first onset of a =10-point decrease with confirmation by the subsequent visit of a =10-point decrease in emotional functioning Items 21-24 scale scores. TTD is reported based on the product-limit (Kaplan-Meier) method for censored data. | Up to approximately 29 months | |
| Secondary | TTD in Systemic Therapy Side Effects Using the EORTC QLQ-BR23 Items 1-4, 6, 7, and 8 Score | EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and four symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. TTD was defined as the time from baseline to the first onset of a =10-point decrease with confirmation by the subsequent visit of a =10-point decrease in systemic therapy side effects Items 1-4, 6, 7 and 8 scale scores. TTD is reported based on the product-limit (Kaplan-Meier) method for censored data. | Up to approximately 29 months | |
| Secondary | TTD in Health-Related QoL Using the EORTC QLQ-C30 Items 29 and 30 Score in Participants With Breast Cancer Susceptibility Gene Mutation (BRCAm) Tumors | EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the QoL question "How would you rate your overall quality of life during the past week?" (Item 30) were each scored on a 7-point scale (1=Very Poor to 7=Excellent), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. TTD was defined as the time from baseline to the first onset of a =10-point decrease with confirmation by the subsequent visit of a =10-point decrease in Items 29 and 30 scale scores. TTD is reported based on the product-limit (Kaplan-Meier) method for censored data. | Baseline and up to approximately 29 months | |
| Secondary | TTD in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score in Participants With BRCAm Tumors | EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. TTD was defined as the time from baseline to the first onset of a =10-point decrease with confirmation by the subsequent visit of a =10-point decrease in physical functioning Items 1 to 5 scale scores. TTD is reported based on the product-limit (Kaplan-Meier) method for censored data. | Up to approximately 29 months | |
| Secondary | TTD in Emotional Functioning Using the EORTC QLQ-C30 Items 21-24 Score in Participants With BRCAm Tumors | EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to 4 questions about their emotional functioning are scored on a 4-point scale (1=Not at All to 4=Very Much), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. TTD was defined as the time from baseline to the first onset of a =10-point decrease with confirmation by the subsequent visit of a =10-point decrease in emotional functioning Items 21-24 scale scores. TTD is reported based on the product-limit (Kaplan-Meier) method for censored data. | Up to approximately 29 months | |
| Secondary | TTD in Systemic Therapy Side Effects Using the EORTC QLQ-BR23 Items 1-4, 6, 7, and 8 Score in Participants With BRCAm Tumors | EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and four symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. TTD was defined as the time from baseline to the first onset of a =10-point decrease with confirmation by the subsequent visit of a =10-point decrease in systemic therapy side effects Items 1-4, 6, 7 and 8 scale scores. TTD is reported based on the product-limit (Kaplan-Meier) method for censored data. | Up to approximately 29 months | |
| Secondary | Number of Participants Who Experienced At Least One Adverse Event (AE) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience at least 1 AE is presented. | Up to approximately 29 months | |
| Secondary | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE is presented. | Up to approximately 29 months |
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