Neoplasms

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Symptoms and General Pathology

Breast Neoplasms

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Breast Diseases

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All Drugs and Chemicals

Anti-Infective Agents

Capecitabine

Paclitaxel

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Liposomal doxorubicin

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Pembrolizumab

Albumin-Bound Paclitaxel

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Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antimetabolites

Participants receive pembrolizumab 200 mg administered by intravenous infusion (IV) on Day 1 of each 21-day cycle (Q3W) PLUS one of four chemotherapy regimens: 1) paclitaxel 90 mg/m\^2 IV on Days 1, 8, and 15 of each 28-day cycle (Q4W), 2) nab-paclitaxel 100 mg/m\^2 IV on Days 1, 8, and 15 Q4W, 3) liposomal doxorubicin 50 mg/m\^2 IV on Day 1 Q4W, OR 4) capecitabine 1000 mg/m\^2 by oral administration (PO) twice a day (BID) on Days 1-14 Q3W for up to 35 administrations.

Participants receive placebo (normal saline or dextrose) IV on Day 1 Q3W PLUS one of four chemotherapy regimens: 1) paclitaxel 90 mg/m\^2 IV on Days 1, 8, and 15 Q4W, 2) nab-paclitaxel 100 mg/m\^2 IV on Days 1, 8, and 15 Q4W, 3) liposomal doxorubicin 50 mg/m\^2 IV on Day 1 Q4W, OR 4) capecitabine 1000 mg/m\^2 PO BID on Days 1-14 Q3W for up to 35 administrations.

pembrolizumab

paclitaxel

nab-paclitaxel

liposomal doxorubicin

capecitabine

normal saline

dextrose

Medical Director

The safety and efficacy of pembrolizumab plus the investigator's choice of chemotherapy will be assessed compared to placebo plus the investigator's choice of chemotherapy in the treatment of chemotherapy-candidate hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) locally recurrent inoperable or metastatic breast cancer.

The primary hypotheses are that the combination of pembrolizumab and chemotherapy is superior to placebo and chemotherapy in regards to Progression-Free Survival (PFS) or overall survival (OS) in participants with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 and ≥10.

Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy for HR+/HER2- Locally Recurrent Inoperable or Metastatic Breast Cancer (MK-3475-B49/KEYNOTE-B49)

A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of Pembrolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy for the Treatment of Chemotherapy-Candidate Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (HR+/HER2-) Locally Recurrent Inoperable or Metastatic Breast Cancer (KEYNOTE-B49)

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The PFS in participants with a CPS of ≥10, as assessed by BICR, will be presented.

PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The PFS in participants with a CPS of ≥1, as assessed by BICR, will be presented.

OS is defined as the time from randomization to death due to any cause. OS for participants with a CPS of ≥10 will be presented.

OS is defined as the time from randomization to death due to any cause. OS for participants with a CPS of ≥1 will be presented.

PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The PFS in participants with a CPS of ≥10, as assessed by investigator, will be presented.

PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The PFS in participants with a CPS of ≥1, as assessed by investigator, will be presented.

ORR is defined as the percentage of participants in the analysis population who achieve confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR for participants with a CPS of ≥10 will be presented.

ORR is defined as the percentage of participants in the analysis population who achieve confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR for participants with a CPS of ≥1 will be presented.

DCR is defined as the percentage of participants who achieve Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD\]) for at least 24 weeks. The percentage of participants who experience a confirmed CR, PR, or SD with a CPS of ≥10 will be presented.

DCR is defined as the percentage of participants who achieve Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD\]) for at least 24 weeks. The percentage of participants who experience a confirmed CR, PR, or SD with a CPS of ≥1 will be presented.

For participants who demonstrate CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, or death from any cause, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. DOR for participants with a CPS of ≥10 will be presented.

For participants who demonstrate CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, or death from any cause, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. DOR for participants with a CPS of ≥1 will be presented.

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score will be presented in participants with a CPS of ≥10. A higher score indicates a better outcome.

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score will be presented in participants with a CPS of ≥1. A higher score indicates a better outcome.

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) 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. The change from baseline in the physical functioning score will be presented in participants with a CPS of ≥10. A higher score indicates a better level of function.

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) 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. The change from baseline in the physical functioning score will be presented in participants with a CPS of ≥1. A higher score indicates a better level of function.

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 4 questions about their emotional functioning (Items 21-24) 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. The change from baseline in the emotional functioning score will be presented in participants with a CPS of ≥10. A higher score indicates a better level of function.

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 4 questions about their emotional functioning (Items 21-24) 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. The change from baseline in the emotional functioning score will be presented in participants with a CPS of ≥1. A higher score indicates a better level of function.

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 3 questions about their fatigue (Items 10, 12, 18) 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. The change from baseline in the fatigue score will be presented in participants with a CPS of ≥10. A lower score indicates a better outcome.

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 3 questions about their fatigue (Items 10, 12, 18) 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. The change from baseline in the fatigue score will be presented in participants with a CPS of ≥1. A lower score indicates a better outcome.

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, including a single-item scale score for diarrhea (QLQ-C30 Item 17). For this item, individual responses to the question "Have you had diarrhea?" are given on a 4-point scale (1=Not at all; 4=Very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the diarrhea score will be presented in participants with a CPS of ≥10. A lower score indicates a better outcome.

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, including a single-item scale score for diarrhea (QLQ-C30 Item 17). For this item, individual responses to the question "Have you had diarrhea?" are given on a 4-point scale (1=Not at all; 4=Very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the diarrhea score will be presented in participants with a CPS of ≥1. A lower score indicates a better outcome.

TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in Global Health Status (GHS; EORTC QLQ-C30 Item 29) \& Quality of Life (QoL; EORTC QLQ-C30 Item 30) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in GHS and QoL combined score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome.

TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in Global Health Status (GHS; EORTC QLQ-C30 Item 29) \& Quality of Life (QoL; EORTC QLQ-C30 Item 30) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in GHS and QoL combined score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome.

TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in physical functioning score (EORTC QLQ-C30 Items 1-5). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in physical functioning score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome.

TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in physical functioning score (EORTC QLQ-C30 Items 1-5). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in physical functioning score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome.

TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in emotional functioning score (EORTC QLQ-C30 Items 21-24). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in emotional functioning score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome.

TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in emotional functioning score (EORTC QLQ-C30 Items 21-24). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in emotional functioning score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome.

TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in fatigue score (EORTC QLQ-C30 Items 10, 12, 18). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in fatigue score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome.

TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in fatigue score (EORTC QLQ-C30 Items 10, 12, 18). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in fatigue score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome.

TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in diarrhea score (EORTC QLQ-C30 Item 17). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in diarrhea score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome.

TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in diarrhea score (EORTC QLQ-C30 Item 17). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in diarrhea score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome.

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 percentage of participants who experience one or more adverse events will be presented.

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 percentage of participants who discontinue study treatment due to an adverse event will be presented.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy for HR+/HER2- Locally Recurrent Inoperable or Metastatic Breast Cancer (MK-3475-B49/KEYNOTE-B49)	NCT04895358	Breast Neoplasm...	pembrolizumab paclitaxel nab-paclitaxel liposomal doxor... capecitabine normal saline dextrose	18 Years -	Merck Sharp & Dohme LLC
Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy for HR+/HER2- Locally Recurrent Inoperable or Metastatic Breast Cancer (MK-3475-B49/KEYNOTE-B49)	NCT04895358	Breast Neoplasm...	pembrolizumab paclitaxel nab-paclitaxel liposomal doxor... capecitabine normal saline dextrose	18 Years -	Merck Sharp & Dohme LLC

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