Clinical Trials List
Protocol NumberMK-7339-009
NCT Number(ClinicalTrials.gov Identfier)NCT04191135
Active
2019-09-01 - 2026-12-31
Phase II
Recruiting2
Terminated3
ICD-10C50.011
Malignant neoplasm of nipple and areola, right female breast
ICD-10C50.012
Malignant neoplasm of nipple and areola, left female breast
ICD-10C50.019
Malignant neoplasm of nipple and areola, unspecified female breast
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9174.0
Malignant neoplasm of female breast, nipple and areola
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)
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
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Sponsor
Merck Sharp & Dohme Corp.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chen-Teng Wu Division of General Surgery
- Chih-Jung Chen Division of General Surgery
- Yao-Chung Wu Division of General Surgery
- Liang-Chih Liu Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Yao-Lung Kuo Division of Plastic Surgery
- Shang-Hung Chen Division of Hematology & Oncology
- Chun-Hui Lee Division of Hematology & Oncology
- 黃建璋 Division of General Surgery
- Ya-Ting Hsu Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- Ya-Ping Chen Division of Hematology & Oncology
- 楊舜如 Division of Hematology & Oncology
- Zhu-Jun Loh Division of General Surgery
- Wei-Pang Chung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Tai-Jan Chiu Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
- 吳佳哲 Division of Hematology & Oncology
- Shau-Hsuan Li Division of Hematology & Oncology
- 賴香蘭 Division of Hematology & Oncology
- 陳彥仰 Division of Hematology & Oncology
- 陳彥豪 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 褚乃銘 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Triple Negative Breast Neoplasms
Objectives
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 prolongs progression-free survival (PFS) compared with chemotherapy plus pembrolizumab.
2.Olaparib plus pembrolizumab is non-inferior to chemotherapy plus pembrolizumab in terms of overall survival (OS).
3.Olaparib plus pembrolizumab prolongs OS compared with chemotherapy plus pembrolizumab.
Test Drug
Pembrolizumab
Active Ingredient
4-[(3-{[4-(cyclopropylcarbonyl)piperazin-1-yl]carbonyl}-4-fluorophenyl)methyl]phthalazin-1(2H)-one
Pembrolizumab (Humanized anti-PD-1 mAb)
Pembrolizumab (Humanized anti-PD-1 mAb)
Dosage Form
Injection
Film-coated Tablet
Film-coated Tablet
Dosage
100 mg/ 4 mL/ vial
100 mg, 150 mg
100 mg, 150 mg
Endpoints
1.Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 72 months ]
2.Overall Survival (OS) [ Time Frame: Up to approximately 72 months ]
2.Overall Survival (OS) [ Time Frame: Up to approximately 72 months ]
Inclution Criteria
Induction Period:
1.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
2.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
3.Has measurable disease based on RECIST 1.1
4.Has provided a recently obtained or archival (no more than 3 years old) core or excisional biopsy of a tumor lesion not previously irradiated
5.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
6.Has a life expectancy ≥27 weeks from the day of first study treatment
7.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)
8.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:
1.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
2.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
3.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
4.Has ECOG performance status of 0 or 1, as assessed within 7 days prior to the start of post-induction study treatment
5.Has no higher than Grade 1 toxicities related to induction therapy (excluding alopecia) prior to randomization
1.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
2.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
3.Has measurable disease based on RECIST 1.1
4.Has provided a recently obtained or archival (no more than 3 years old) core or excisional biopsy of a tumor lesion not previously irradiated
5.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
6.Has a life expectancy ≥27 weeks from the day of first study treatment
7.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)
8.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:
1.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
2.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
3.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
4.Has ECOG performance status of 0 or 1, as assessed within 7 days prior to the start of post-induction study treatment
5.Has no higher than Grade 1 toxicities related to induction therapy (excluding alopecia) prior to randomization
Exclusion Criteria
Induction Period:
1.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
2.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
3.Has an active autoimmune disease that has required systemic treatment in the past 2 years
4.Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
5.Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML
6.Has a history of (non-infectious) pneumonitis\interstitial lung disease that required steroids or current pneumonitis\interstitial lung disease
7.Has active, or a history of, interstitial lung disease
8.Has a known history of active tuberculosis
9.Has an active infection requiring systemic therapy
10.Has a known history of human immunodeficiency virus (HIV) infection
11.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
12.Has a history of class II-IV congestive heart failure or myocardial infarction within 6 months of first study treatment
13.Has neuropathy ≥Grade 2
14.Has not recovered (eg, to ≤Grade 1 or to baseline) from AEs due to a previously administered therapy
15.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
16.Has severe hypersensitivity (≥Grade 3) to the study treatments and/or any of their excipients
17.Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
18.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
19.Is a WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation
20.Has received prior therapy with either olaparib or any other poly adenosine diphosphate ribose polymerase (PARP) inhibitor
21.Has received prior radiotherapy within 2 weeks of start of study treatment
22.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
23.Has had an allogenic tissue/solid organ transplant.
24.Has received previous allogenic bone marrow transplant or double umbilical cord transplantation (dUCBT)
25.Has had major surgery within 2 weeks of starting study treatment or has not recovered from any effects of any major surgery
26.Has received a live or live-attenuated vaccine within 30 days prior to first study treatment
27.Is receiving any medication prohibited in combination with study chemotherapies unless medication was stopped within 7 days prior to first study treatment
28.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
29.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
30.Has presence of uncontrolled, potentially reversible cardiac conditions, as judged by the investigator
31.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
32.Is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption)
33.Is unlikely to comply with the study procedures, restrictions, and requirements of the study; as judged by the investigator
Post-induction Period:
1.Has severe hypersensitivity (≥Grade 3) to the study treatments and/or any of their excipients
2.Has permanently discontinued from both carboplatin and gemcitabine during induction due to toxicity
3.Has permanently discontinued from pembrolizumab during induction due to toxicity
4.Has received less than 4 cycles of chemotherapy plus pembrolizumab during induction
5.Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
6.Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study
1.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
2.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
3.Has an active autoimmune disease that has required systemic treatment in the past 2 years
4.Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
5.Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML
6.Has a history of (non-infectious) pneumonitis\interstitial lung disease that required steroids or current pneumonitis\interstitial lung disease
7.Has active, or a history of, interstitial lung disease
8.Has a known history of active tuberculosis
9.Has an active infection requiring systemic therapy
10.Has a known history of human immunodeficiency virus (HIV) infection
11.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
12.Has a history of class II-IV congestive heart failure or myocardial infarction within 6 months of first study treatment
13.Has neuropathy ≥Grade 2
14.Has not recovered (eg, to ≤Grade 1 or to baseline) from AEs due to a previously administered therapy
15.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
16.Has severe hypersensitivity (≥Grade 3) to the study treatments and/or any of their excipients
17.Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
18.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
19.Is a WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation
20.Has received prior therapy with either olaparib or any other poly adenosine diphosphate ribose polymerase (PARP) inhibitor
21.Has received prior radiotherapy within 2 weeks of start of study treatment
22.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
23.Has had an allogenic tissue/solid organ transplant.
24.Has received previous allogenic bone marrow transplant or double umbilical cord transplantation (dUCBT)
25.Has had major surgery within 2 weeks of starting study treatment or has not recovered from any effects of any major surgery
26.Has received a live or live-attenuated vaccine within 30 days prior to first study treatment
27.Is receiving any medication prohibited in combination with study chemotherapies unless medication was stopped within 7 days prior to first study treatment
28.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
29.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
30.Has presence of uncontrolled, potentially reversible cardiac conditions, as judged by the investigator
31.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
32.Is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption)
33.Is unlikely to comply with the study procedures, restrictions, and requirements of the study; as judged by the investigator
Post-induction Period:
1.Has severe hypersensitivity (≥Grade 3) to the study treatments and/or any of their excipients
2.Has permanently discontinued from both carboplatin and gemcitabine during induction due to toxicity
3.Has permanently discontinued from pembrolizumab during induction due to toxicity
4.Has received less than 4 cycles of chemotherapy plus pembrolizumab during induction
5.Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
6.Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study
The Estimated Number of Participants
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Taiwan
11 participants
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Global
260 participants
