Study of Olaparib Plus Pembrolizumab Versus Chemotherapy Plus Pembrolizumab After Induction With First-Line Chemotherapy Plus Pembrolizumab in Triple Negative Breast Cancer (TNBC) (MK-7339-009/KEYLYNK-009)

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04191135
• Other study ID #: 7339-009
• Secondary ID: MK-7339-009KEYLY
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 19, 2019
• Est. completion date: November 18, 2025

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to 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.

Recruitment information / eligibility

• 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

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Biological:
• Pembrolizumab
intravenous (IV) infusion

Drug:
• Olaparib
oral tablets
• Carboplatin
IV infusion
• Gemcitabine
IV infusion

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Canada,  Chile,  Colombia,  France,  Germany,  Hungary,  Ireland,  Japan,  Korea, Republic of,  Poland,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

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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