Triple Negative Breast Cancer (TNBC)
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1(PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Brief summary
The study will consist of two parts. In Part 1, the safety of pembrolizumab (MK-3475) in combination with one of three different chemotherapies will be assessed in the treatment of locally recurrent inoperable or metastatic triple negative breast cancer (TNBC), which has not been previously treated with chemotherapy. In Part 2, the safety and efficacy of pembrolizumab plus background chemotherapy will be assessed compared to the safety and efficacy of placebo plus background chemotherapy in the treatment of locally recurrent inoperable or metastatic TNBC, which has not been previously treated with chemotherapy. The primary hypotheses are that: 1. the combination of pembrolizumab and chemotherapy prolongs Progression-Free Survival (PFS) compared to placebo and chemotherapy in: * all participants, * participants with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 tumors, and * participants with PD-L1 CPS ≥10 tumors, and 2. the combination of pembrolizumab and chemotherapy prolongs Overall Survival (OS) compared to placebo and chemotherapy in: * all participants, * participants with PD-L1 CPS ≥1 tumors, and * participants with PD-L1 CPS ≥10 tumors.
Interventions
BIOLOGICALPembrolizumab
IV infusion
DRUGNab-paclitaxel
IV infusion
DRUGPaclitaxel
IV infusion
DRUGGemcitabine
IV infusion
DRUGCarboplatin
IV infusion
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has locally recurrent inoperable breast cancer not previously treated with chemotherapy and which cannot be treated with curative intent OR has metastatic breast cancer not previously treated with chemotherapy. * Has centrally confirmed TNBC, as defined by the most recent American Society of Clinical Oncology/college of American Pathologists (ASCO/CAP) guidelines. * Has completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months elapsed between the completion of treatment with curative intent (e.g., date of primary breast tumor surgery or date of last adjuvant chemotherapy administration, whichever occurred last) and first documented local or distant disease recurrence. * Has been treated with (neo)adjuvant anthracycline, if they received systemic treatment in the (neo)adjuvant setting, unless anthracycline was contraindicated or not considered the best treatment option for the participant in the opinion of the treating physician. * Has measurable disease based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by local radiology review. * Has provided recently or newly obtained core or excisional biopsy from a locally recurrent inoperable or metastatic tumor lesion for central determination of TNBC status and PD-L1 expression, unless contraindicated due to site inaccessibility and/or participant safety concerns. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 10 days prior to the start of study drug. * Has a life expectancy ≥12 weeks from randomization. * Demonstrates adequate organ function, within 10 days prior to the start of study drug. * Female participants are eligible to participate if they are not pregnant or breastfeeding AND they are not a woman of childbearing potential (WOCBP) OR is a WOCBP using a contraceptive method that is highly effective or is abstinent from heterosexual intercourse during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention AND has a negative highly-sensitive pregnancy test (\[urine or serum\] as required by local regulations) within 24 hours (urine) or 72 hours (serum) before the first dose of study intervention. * Male participants are eligible to participate if they agree to refrain from donating sperm during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention PLUS be abstinent from heterosexual intercourse OR must agree to use contraception unless confirmed to be azoospermic.
Exclusion criteria
* Is currently participating in a clinical study and receiving an investigational agent and/or using an investigational device, or has participated in a clinical study and received an investigational agent and/or used an investigational device within 4 weeks prior to randomization. * Has not recovered (e.g., to ≤ Grade 1 or to baseline) from AEs due to a previously administered therapy. * Has neuropathy ≥ Grade 2. * Has an active autoimmune disease that has required systemic treatment in the past 2 years (e.g., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization. * Has a known additional malignancy that progressed or required active treatment within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, and in situ cervical cancer. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they have stable brain metastases and did not receive chemotherapy for metastatic breast cancer. * Has history of (non-infectious) pneumonitis that required steroids or current pneumonitis. * Has active, or a history of, interstitial lung disease. * Has a known history of active tuberculosis (TB). * Has an active infection requiring systemic therapy. * Has a history of Class II-IV congestive heart failure or myocardial infarction within 6 months of randomization. * Has a known psychiatric or substance abuse disorders that would interfere with cooperation 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 120 days (or longer as specified by local institutional guidelines) after the last dose of study drug. * Has received prior therapy with an anti-programmed cell death 1 (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 Merck pembrolizumab (MK-3475) clinical studies. * Has a known history of human immunodeficiency virus (HIV). * Has known active hepatitis B or hepatitis C. * Has received a live vaccine within 30 days prior to randomization. * Has a known history of hypersensitivity or allergy to pembrolizumab and any of its components and/or to any of the study chemotherapies (e.g., nab-paclitaxel, paclitaxel, gemcitabine, or carboplatin) and any of their components. * Is receiving any medication prohibited in combination with study chemotherapies as described in the respective product labels, unless medication was stopped within 7 days prior to randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Participants Who Experienced an Adverse Event (AE) - All Participants | Up to approximately 39 months | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Part 1: Percentage of Participants Who Discontinued Study Drug Due to an AE - All Participants | Up to approximately 39 months | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Part 2: Progression-Free Survival (PFS) - All Participants | Up to approximately 53 months | Progression-free survival 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) based on assessments 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 of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. |
| Part 2: PFS - Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Tumors | Up to approximately 53 months | Progression-free survival was defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by 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 of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. |
| Part 2: PFS - Participants With PD-L1 CPS ≥10 Tumors | Up to approximately 53 months | Progression-free survival was defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by 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 of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. |
| Part 2: Overall Survival (OS) - All Participants | Up to approximately 53 months | Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. |
| Part 2: OS - Participants With PD-L1 CPS ≥1 Tumors | Up to approximately 53 months | Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. |
| Part 2: OS - Participants With PD-L1 CPS ≥10 Tumors | Up to approximately 53 months | Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: DCR - Participants With PD-L1 CPS ≥10 Tumors | Up to approximately 53 months | Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1. |
| Part 2: Percentage of Participants Who Experienced an AE- All Participants | Up to approximately 81 months | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Part 2: Percentage of Participants Who Discontinued Study Drug Due to an AE- All Participants | Up to approximately 81 months | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Part 2: Change From Baseline to Week 15 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score- All Participants | Baseline and Week 15 | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions How would you rate your overall health during the past week? (Item 29) and How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented. |
| Part 2: Objective Response Rate (ORR) - All Participants | Up to approximately 53 months | Objective response rate is defined as the percentage of participants in the analysis population who have a 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). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented. |
| Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score-Participants With PD-L1 CPS ≥10 Tumors | Baseline and Week 15 | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions How would you rate your overall health during the past week? (Item 29) and How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented. |
| Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23)-All Participants | Baseline and Week 15 | 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 were 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 denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented. |
| Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23 - Participants With PD-L1 CPS ≥1 Tumors | Baseline and Week 15 | 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 were 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 denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented. |
| Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23- Participants With PD-L1 CPS ≥10 Tumors | Baseline and Week 15 | 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 denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented. |
| Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score - Participants With PD-L1 CPS ≥1 Tumors | Baseline and Week 15 | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions How would you rate your overall health during the past week? (Item 29) and How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented. |
| Part 2: ORR - Participants With PD-L1 CPS ≥1 Tumors | Up to approximately 53 months | Objective response rate is defined as the percentage of participants in the analysis population who have a 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). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented. |
| Part 2: ORR - Participants With PD-L1 CPS ≥10 Tumors | Up to approximately 53 months | Objective response rate is defined as the percentage of participants in the analysis population who have a 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). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented. |
| Part 2: Duration of Response (DOR) - All Participants | Up to approximately 53 months | For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. |
| Part 2: DOR - Participants With PD-L1 CPS ≥1 Tumors | Up to approximately 53 months | For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. |
| Part 2: DOR - Participants With PD-L1 CPS ≥10 Tumors | Up to approximately 53 months | For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. |
| Part 2: Disease Control Rate (DCR) - All Participants | Up to approximately 53 months | Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1. |
| Part 2: DCR - Participants With PD-L1 CPS ≥1 Tumors | Up to approximately 53 months | Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1. |
Participant flow
Pre-assignment details
35 participants were randomized to Part 1 (Safety Run-in) of the study, and 847 participants were randomized in Part 2 (phase 3) of the study. 12 participants randomized to the Part 2: Pembrolizumab + Chemotherapy arm received a second course of pembrolizumab at the investigator's discretion. Per protocol, response/progression or adverse events (AEs) that occurred during the second course were not counted towards efficacy outcome measures or safety outcome measures respectively.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS nab-paclitaxel IV on Days 1, 8 and 15 of each 28-day cycle. | 11 |
| Part 1: Pembrolizumab + Paclitaxel Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS paclitaxel IV on Days 1, 8 and 15 of each 28-day cycle. | 14 |
| Part 1: Pembrolizumab + Gemcitabine/Carboplatin Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS gemcitabine/carboplatin (gemcitabine) and an Area Under the Curve (AUC) 2 (carboplatin) on Days 1 and 8 of each 21-day cycle. | 10 |
| Part 2: Pembrolizumab + Chemotherapy Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle. Qualified participants who received first course of pembrolizumab but continued to experience disease progression were eligible to initiate a second course of pembrolizumab IV Q3W for up to 17 administrations (up to \
1 year). | 566 |
| Part 2: Placebo + Chemotherapy Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m\^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m\^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m\^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle. | 281 |
| Total | 882 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 9 | 12 | 9 | 475 | 244 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Sponsor Decision | 1 | 1 | 0 | 34 | 17 |
| Overall Study | Transferred to extension study | 1 | 1 | 1 | 32 | 11 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 25 | 8 |
Baseline characteristics
| Characteristic | Part 1: Pembrolizumab + Nab-Paclitaxel | Part 1: Pembrolizumab + Paclitaxel | Part 1: Pembrolizumab + Gemcitabine/Carboplatin | Part 2: Pembrolizumab + Chemotherapy | Part 2: Placebo + Chemotherapy | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 54.6 Years STANDARD_DEVIATION 13.5 | 60.4 Years STANDARD_DEVIATION 15.3 | 59.6 Years STANDARD_DEVIATION 11.7 | 53.5 Years STANDARD_DEVIATION 12.7 | 53.0 Years STANDARD_DEVIATION 12.7 | 53.5 Years STANDARD_DEVIATION 12.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 116 Participants | 48 Participants | 165 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 14 Participants | 10 Participants | 423 Participants | 218 Participants | 674 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 27 Participants | 15 Participants | 43 Participants |
| PD-L1 Status (CPS Cutoff of 10) PD-L1 CPS <10 | 10 Participants | 5 Participants | 6 Participants | 346 Participants | 178 Participants | 545 Participants |
| PD-L1 Status (CPS Cutoff of 10) PD-L1 CPS ≥10 | 1 Participants | 9 Participants | 4 Participants | 220 Participants | 103 Participants | 337 Participants |
| Programmed Cell Death Ligand 1 (PD-L1) Status (Combined Positive Score [CPS] Cutoff of 1) PD-L1 CPS <1 | 3 Participants | 2 Participants | 3 Participants | 141 Participants | 70 Participants | 219 Participants |
| Programmed Cell Death Ligand 1 (PD-L1) Status (Combined Positive Score [CPS] Cutoff of 1) PD-L1 CPS ≥1 | 8 Participants | 12 Participants | 7 Participants | 425 Participants | 211 Participants | 663 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 11 Participants | 1 Participants | 12 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 7 Participants | 4 Participants | 123 Participants | 52 Participants | 190 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 20 Participants | 17 Participants | 38 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 11 Participants | 8 Participants | 19 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 17 Participants | 8 Participants | 25 Participants |
| Race (NIH/OMB) White | 6 Participants | 7 Participants | 6 Participants | 384 Participants | 195 Participants | 598 Participants |
| Sex: Female, Male Female | 11 Participants | 14 Participants | 10 Participants | 566 Participants | 281 Participants | 882 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 11 | 12 / 14 | 9 / 10 | 484 / 566 | 5 / 12 | 249 / 281 |
| other Total, other adverse events | 13 / 13 | 10 / 10 | 11 / 11 | 551 / 562 | 11 / 12 | 273 / 281 |
| serious Total, serious adverse events | 3 / 13 | 4 / 10 | 9 / 11 | 169 / 562 | 3 / 12 | 68 / 281 |
Outcome results
Primary
Part 1: Percentage of Participants Who Discontinued Study Drug Due to an AE - All Participants
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Time frame: Up to approximately 39 months
Population: All randomly assigned participants who received at least 1 dose of study intervention were included in the group corresponding to the study intervention actually received. Four participants assigned to the pembrolizumab + paclitaxel group received incorrect chemotherapy in error: 3 participants received pembrolizumab + nab-paclitaxel and 1 received pembrolizumab + gemcitabine/carboplatin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 1: Percentage of Participants Who Discontinued Study Drug Due to an AE - All Participants | 38.5 Percentage of Participants |
| Part 1: Pembrolizumab + Paclitaxel | Part 1: Percentage of Participants Who Discontinued Study Drug Due to an AE - All Participants | 50.0 Percentage of Participants |
| Part 1: Pembrolizumab + Gemcitabine/Carboplatin | Part 1: Percentage of Participants Who Discontinued Study Drug Due to an AE - All Participants | 27.3 Percentage of Participants |
Primary
Part 1: Percentage of Participants Who Experienced an Adverse Event (AE) - All Participants
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Time frame: Up to approximately 39 months
Population: All randomly assigned participants who received at least 1 dose of study intervention were included in the group corresponding to the study intervention actually received. Four participants assigned to the pembrolizumab + paclitaxel group received incorrect chemotherapy in error: 3 participants received pembrolizumab + nab-paclitaxel and 1 received pembrolizumab + gemcitabine/carboplatin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 1: Percentage of Participants Who Experienced an Adverse Event (AE) - All Participants | 100.0 Percentage of Participants |
| Part 1: Pembrolizumab + Paclitaxel | Part 1: Percentage of Participants Who Experienced an Adverse Event (AE) - All Participants | 100.0 Percentage of Participants |
| Part 1: Pembrolizumab + Gemcitabine/Carboplatin | Part 1: Percentage of Participants Who Experienced an Adverse Event (AE) - All Participants | 100.0 Percentage of Participants |
Primary
Part 2: OS - Participants With PD-L1 CPS ≥10 Tumors
Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Time frame: Up to approximately 53 months
Population: Participants with PD-L1 CPS ≥10 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: OS - Participants With PD-L1 CPS ≥10 Tumors | 23.0 Months |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: OS - Participants With PD-L1 CPS ≥10 Tumors | 16.1 Months |
p-value: 0.009395% CI: [0.55, 0.95]Log Rank
Primary
Part 2: OS - Participants With PD-L1 CPS ≥1 Tumors
Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Time frame: Up to approximately 53 months
Population: Participants with PD-L1 CPS ≥1 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: OS - Participants With PD-L1 CPS ≥1 Tumors | 17.6 Months |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: OS - Participants With PD-L1 CPS ≥1 Tumors | 16.0 Months |
p-value: 0.056395% CI: [0.72, 1.04]Log Rank
Primary
Part 2: Overall Survival (OS) - All Participants
Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Time frame: Up to approximately 53 months
Population: Participants were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: Overall Survival (OS) - All Participants | 17.2 Months |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: Overall Survival (OS) - All Participants | 15.5 Months |
p-value: 0.079795% CI: [0.76, 1.05]Log Rank
Primary
Part 2: PFS - Participants With PD-L1 CPS ≥10 Tumors
Progression-free survival was defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by 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 of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Time frame: Up to approximately 53 months
Population: Participants with PD-L1 CPS ≥10 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: PFS - Participants With PD-L1 CPS ≥10 Tumors | 9.7 Months |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: PFS - Participants With PD-L1 CPS ≥10 Tumors | 5.6 Months |
p-value: 0.001895% CI: [0.5, 0.88]Log Rank
Primary
Part 2: PFS - Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Tumors
Progression-free survival was defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by 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 of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Time frame: Up to approximately 53 months
Population: Participants with PD-L1 CPS ≥1 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: PFS - Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Tumors | 7.6 Months |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: PFS - Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Tumors | 5.6 Months |
p-value: 0.001695% CI: [0.62, 0.91]Log Rank
Primary
Part 2: Progression-Free Survival (PFS) - All Participants
Progression-free survival 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) based on assessments 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 of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Time frame: Up to approximately 53 months
Population: Participants were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: Progression-Free Survival (PFS) - All Participants | 7.5 Months |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: Progression-Free Survival (PFS) - All Participants | 5.6 Months |
p-value: 0.01295% CI: [0.7, 0.98]Log Rank
Secondary
Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score-Participants With PD-L1 CPS ≥10 Tumors
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions How would you rate your overall health during the past week? (Item 29) and How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented.
Time frame: Baseline and Week 15
Population: All randomized participants with PD-L1 CPS ≥10 tumors who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score-Participants With PD-L1 CPS ≥10 Tumors | -2.69 Scores on a scale |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score-Participants With PD-L1 CPS ≥10 Tumors | -0.88 Scores on a scale |
Secondary
Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score - Participants With PD-L1 CPS ≥1 Tumors
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions How would you rate your overall health during the past week? (Item 29) and How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented.
Time frame: Baseline and Week 15
Population: All randomized participants with PD-L1 CPS ≥1 tumors who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score - Participants With PD-L1 CPS ≥1 Tumors | -3.92 Scores on a scale |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score - Participants With PD-L1 CPS ≥1 Tumors | -3.15 Scores on a scale |
Secondary
Part 2: Change From Baseline to Week 15 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score- All Participants
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions How would you rate your overall health during the past week? (Item 29) and How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented.
Time frame: Baseline and Week 15
Population: All randomized participants who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: Change From Baseline to Week 15 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score- All Participants | -3.52 Scores on a scale |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: Change From Baseline to Week 15 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score- All Participants | -2.15 Scores on a scale |
Secondary
Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23)-All Participants
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 were 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 denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented.
Time frame: Baseline and Week 15
Population: All randomized participants who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23)-All Participants | 12.50 Scores on a scale |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23)-All Participants | 12.36 Scores on a scale |
Secondary
Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23- Participants With PD-L1 CPS ≥10 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 denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented.
Time frame: Baseline and Week 15
Population: All randomized participants with PD-L1 CPS ≥10 tumors who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23- Participants With PD-L1 CPS ≥10 Tumors | 13.56 Scores on a scale |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23- Participants With PD-L1 CPS ≥10 Tumors | 13.26 Scores on a scale |
Secondary
Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23 - Participants With PD-L1 CPS ≥1 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 were 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 denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented.
Time frame: Baseline and Week 15
Population: All randomized participants with PD-L1 CPS ≥1 tumors who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23 - Participants With PD-L1 CPS ≥1 Tumors | 13.00 Scores on a scale |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23 - Participants With PD-L1 CPS ≥1 Tumors | 11.86 Scores on a scale |
Secondary
Part 2: DCR - Participants With PD-L1 CPS ≥10 Tumors
Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1.
Time frame: Up to approximately 53 months
Population: Participants with PD-L1 CPS ≥10 tumors at baseline were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: DCR - Participants With PD-L1 CPS ≥10 Tumors | 65.0 Percentage of Participants |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: DCR - Participants With PD-L1 CPS ≥10 Tumors | 54.4 Percentage of Participants |
p-value: 0.032795% CI: [-0.7, 22.3]Cochran-Mantel-Haenszel
Secondary
Part 2: DCR - Participants With PD-L1 CPS ≥1 Tumors
Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1.
Time frame: Up to approximately 53 months
Population: Participants with PD-L1 CPS ≥1 tumors at baseline were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: DCR - Participants With PD-L1 CPS ≥1 Tumors | 58.6 Percentage of Participants |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: DCR - Participants With PD-L1 CPS ≥1 Tumors | 53.6 Percentage of Participants |
p-value: 0.116495% CI: [-3.2, 13.1]Cochran-Mantel-Haenszel
Secondary
Part 2: Disease Control Rate (DCR) - All Participants
Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1.
Time frame: Up to approximately 53 months
Population: Participants were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: Disease Control Rate (DCR) - All Participants | 56.0 Percentage of Participants |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: Disease Control Rate (DCR) - All Participants | 51.2 Percentage of Participants |
p-value: 0.096695% CI: [-2.4, 11.8]Cochran-Mantel-Haenszel
Secondary
Part 2: DOR - Participants With PD-L1 CPS ≥10 Tumors
For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.
Time frame: Up to approximately 53 months
Population: All randomized participants with PD-LI CPS ≥10 tumors regardless of whether or not they received study treatment, who demonstrated a confirmed response (CR or PR). Participants were included in the treatment arm to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: DOR - Participants With PD-L1 CPS ≥10 Tumors | NA Months |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: DOR - Participants With PD-L1 CPS ≥10 Tumors | 7.3 Months |
Secondary
Part 2: DOR - Participants With PD-L1 CPS ≥1 Tumors
For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.
Time frame: Up to approximately 53 months
Population: All randomized participants with PD-LI CPS ≥1 tumors regardless of whether or not they received study treatment, who demonstrated a confirmed response (CR or PR). Participants were included in the treatment arm to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: DOR - Participants With PD-L1 CPS ≥1 Tumors | NA Months |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: DOR - Participants With PD-L1 CPS ≥1 Tumors | 6.8 Months |
Secondary
Part 2: Duration of Response (DOR) - All Participants
For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.
Time frame: Up to approximately 53 months
Population: All randomized participants, regardless of whether or not they received study treatment, who demonstrated a confirmed response (CR or PR). Participants were included in the treatment arm to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: Duration of Response (DOR) - All Participants | NA Months |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: Duration of Response (DOR) - All Participants | 6.5 Months |
Secondary
Part 2: Objective Response Rate (ORR) - All Participants
Objective response rate is defined as the percentage of participants in the analysis population who have a 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). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented.
Time frame: Up to approximately 53 months
Population: Participants were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: Objective Response Rate (ORR) - All Participants | 40.8 Percentage of Participants |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: Objective Response Rate (ORR) - All Participants | 37.0 Percentage of Participants |
p-value: 0.141395% CI: [-3.2, 10.6]Cochran-Mantel-Haenszel
Secondary
Part 2: ORR - Participants With PD-L1 CPS ≥10 Tumors
Objective response rate is defined as the percentage of participants in the analysis population who have a 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). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented.
Time frame: Up to approximately 53 months
Population: Participants with PD-L1 CPS ≥10 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: ORR - Participants With PD-L1 CPS ≥10 Tumors | 52.7 Percentage of Participants |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: ORR - Participants With PD-L1 CPS ≥10 Tumors | 40.8 Percentage of Participants |
p-value: 0.021395% CI: [0.4, 23.4]Cochran-Mantel-Haenszel
Secondary
Part 2: ORR - Participants With PD-L1 CPS ≥1 Tumors
Objective response rate is defined as the percentage of participants in the analysis population who have a 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). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented.
Time frame: Up to approximately 53 months
Population: Participants with PD-L1 CPS ≥1 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: ORR - Participants With PD-L1 CPS ≥1 Tumors | 44.9 Percentage of Participants |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: ORR - Participants With PD-L1 CPS ≥1 Tumors | 38.9 Percentage of Participants |
p-value: 0.072595% CI: [-2.1, 14]Cochran-Mantel-Haenszel
Secondary
Part 2: Percentage of Participants Who Discontinued Study Drug Due to an AE- All Participants
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Time frame: Up to approximately 81 months
Population: All randomized participants who received at least 1 dose of study intervention. Participants were included in the group corresponding to the study intervention actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: Percentage of Participants Who Discontinued Study Drug Due to an AE- All Participants | 20.5 Percentage of Participants |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: Percentage of Participants Who Discontinued Study Drug Due to an AE- All Participants | 13.2 Percentage of Participants |
Secondary
Part 2: Percentage of Participants Who Experienced an AE- All Participants
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Time frame: Up to approximately 81 months
Population: All randomized participants who received at least 1 dose of study intervention. Participants were included in the group corresponding to the study intervention actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Pembrolizumab + Nab-Paclitaxel | Part 2: Percentage of Participants Who Experienced an AE- All Participants | 98.6 Percentage of Participants |
| Part 1: Pembrolizumab + Paclitaxel | Part 2: Percentage of Participants Who Experienced an AE- All Participants | 98.2 Percentage of Participants |