Trial Outcomes & Findings for Study of Single Agent Pembrolizumab (MK-3475) Versus Single Agent Chemotherapy for Metastatic Triple Negative Breast Cancer (MK-3475-119/KEYNOTE-119) (NCT NCT02555657)

NCT ID: NCT02555657

Last Updated: 2021-12-10

Results Overview

Overall survival (OS) was defined as the time from randomization to death due to any cause.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

622 participants

Primary outcome timeframe

Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)

Results posted on

2021-12-10

Participant Flow

Per protocol, response/progression or adverse events during the second pembrolizumab course were not counted towards efficacy outcome measures or safety outcome measures respectively.

Participant milestones

Participant milestones
Measure	Pembrolizumab Participants received pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations (up to \~2 years). Qualified participants who received first course of pembrolizumab but continued to experience disease progression may have, at investigator's discretion, initiated a second course of pembrolizumab at 200 mg IV Q3W for up to 17 administrations (up to \~1 year).	Chemotherapy Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Overall Study STARTED	312	310
Overall Study Treated	309	292
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	312	310

Reasons for withdrawal

Reasons for withdrawal
Measure	Pembrolizumab Participants received pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations (up to \~2 years). Qualified participants who received first course of pembrolizumab but continued to experience disease progression may have, at investigator's discretion, initiated a second course of pembrolizumab at 200 mg IV Q3W for up to 17 administrations (up to \~1 year).	Chemotherapy Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Overall Study Death	274	262
Overall Study Physician Decision	0	1
Overall Study Sponsor Decision	27	15
Overall Study Withdrawal by Subject	11	32

Baseline Characteristics

Study of Single Agent Pembrolizumab (MK-3475) Versus Single Agent Chemotherapy for Metastatic Triple Negative Breast Cancer (MK-3475-119/KEYNOTE-119)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab n=312 Participants Participants received pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations (up to \~2 years). Qualified participants who received first course of pembrolizumab but continued to experience disease progression may have, at investigator's discretion, initiated a second course of pembrolizumab at 200 mg IV Q3W for up to 17 administrations (up to \~1 year).	Chemotherapy n=310 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.	Total n=622 Participants Total of all reporting groups
Age, Continuous	51.4 Years STANDARD_DEVIATION 11.4 • n=5 Participants	52.6 Years STANDARD_DEVIATION 11.2 • n=7 Participants	52.0 Years STANDARD_DEVIATION 11.3 • n=5 Participants
Sex: Female, Male Female	312 Participants n=5 Participants	308 Participants n=7 Participants	620 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Asian	87 Participants n=5 Participants	101 Participants n=7 Participants	188 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants	4 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) White	183 Participants n=5 Participants	180 Participants n=7 Participants	363 Participants n=5 Participants
Race (NIH/OMB) More than one race	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants	9 Participants n=7 Participants	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)

Population: All participants with PD-L1 CPS ≥10 who were included in a treatment group at randomization

Overall survival (OS) was defined as the time from randomization to death due to any cause.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=96 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=98 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Overall Survival in Participants With Programmed Cell Death Ligand 1 (PD-L1) With Combined Positive Score (CPS) ≥10	12.7 Months Interval 9.9 to 16.3	11.6 Months Interval 8.3 to 13.7

PRIMARY outcome

Timeframe: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)

Population: All participants with PD-L1 CPS ≥1 who were included in a treatment group at randomization

Overall survival (OS) was defined as the time from randomization to death due to any cause.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=203 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=202 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Overall Survival in Participants With PD-L1 CPS ≥1	10.7 Months Interval 9.3 to 12.5	10.2 Months Interval 7.9 to 12.6

PRIMARY outcome

Timeframe: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)

Population: All participants who were included in a treatment group at randomization

Overall survival (OS) was defined as the time from randomization to death due to any cause.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=312 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=310 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Overall Survival in All Participants	9.9 Months Interval 8.3 to 11.4	10.8 Months Interval 9.1 to 12.6

SECONDARY outcome

Timeframe: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)

Population: All participants with PD-L1 CPS ≥10 who were included in a treatment group at randomization

Overall Response Rate (ORR), based on a Blinded Independent Central Review (BICR) assessment per RECIST 1.1, was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions).

Outcome measures

Outcome measures
Measure	Pembrolizumab n=96 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=98 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Overall Response Rate Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With PD-L1 CPS ≥10	17.7 Percentage of participants Interval 10.7 to 26.8	9.2 Percentage of participants Interval 4.3 to 16.7

SECONDARY outcome

Timeframe: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)

Population: All participants with PD-L1 CPS ≥1 who were included in a treatment group at randomization

Overall Response Rate (ORR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions).

Outcome measures

Outcome measures
Measure	Pembrolizumab n=203 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=202 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Overall Response Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1	12.3 Percentage of participants Interval 8.1 to 17.6	9.4 Percentage of participants Interval 5.8 to 14.3

SECONDARY outcome

Timeframe: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)

Population: All participants who were included in a treatment group at randomization

Outcome measures

Outcome measures
Measure	Pembrolizumab n=312 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=310 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Overall Response Rate Per RECIST 1.1 in All Participants	9.6 Percentage of participants Interval 6.6 to 13.4	10.6 Percentage of participants Interval 7.4 to 14.6

SECONDARY outcome

Timeframe: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)

Population: All participants with PD-L1 CPS ≥10 who were included in a treatment group at randomization

Progression-Free Survival (PFS), based on BICR assessment per RECIST 1.1, was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred 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 demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=96 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=98 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥10	2.1 Months Interval 2.0 to 2.5	3.4 Months Interval 2.3 to 4.1

SECONDARY outcome

Timeframe: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)

Population: All participants with PD-L1 CPS ≥1 who were included in a treatment group at randomization

Outcome measures

Outcome measures
Measure	Pembrolizumab n=203 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=202 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥1	2.1 Months Interval 2.0 to 2.1	3.1 Months Interval 2.3 to 4.0

SECONDARY outcome

Timeframe: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)

Population: All participants who were included in a treatment group at randomization

Outcome measures

Outcome measures
Measure	Pembrolizumab n=312 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=310 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Progression-Free Survival Per RECIST 1.1 in All Participants	2.1 Months Interval 2.0 to 2.1	3.3 Months Interval 2.7 to 4.0

SECONDARY outcome

Timeframe: Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019)

Population: All randomized participants with PD-L1 CPS ≥10, 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.

For participants with PD-L1 CPS ≥10 who demonstrated a 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, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=17 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=9 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 Who Had a Confirmed Response	NA Months Interval 2.2 to NA=Median DOR not reached at time of data cutoff due to insufficient number of responding participants with relapse NA=DOR upper limit not reached at time of data cutoff due to insufficient number of responding participants with relapse	7.1 Months Interval 3.8 to NA=DOR upper limit not reached at time of data cutoff due to insufficient number of responding participants with relapse

SECONDARY outcome

Timeframe: Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019)

Population: All randomized participants with PD-L1 CPS ≥1, 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.

For participants with PD-L1 CPS ≥1 who demonstrated a 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, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=25 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=19 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 Who Had a Confirmed Response	12.2 Months Interval 2.2 to NA=DOR upper limit not reached at time of data cutoff due to insufficient number of responding participants with relapse	NA Months NA=Median DOR not reached at time of data cutoff due to insufficient number of responding participants with relapse NA=DOR lower limit not reached at time of data cutoff due to insufficient number of responding participants with relapse NA=DOR upper limit not reached at time of data cutoff due to insufficient number of responding participants with relapse

SECONDARY outcome

Timeframe: Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019)

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.

For participants who demonstrated a 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, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=30 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=33 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Duration of Response Per RECIST 1.1 in All Participants Who Had a Confirmed Response	12.2 Months Interval 2.2 to NA=DOR upper limit not reached at time of data cutoff due to insufficient number of responding participants with relapse	NA Months NA=Median DOR not reached at time of data cutoff due to insufficient number of responding participants with relapse NA=DOR lower limit not reached at time of data cutoff due to insufficient number of responding participants with relapse NA=DOR upper limit not reached at time of data cutoff due to insufficient number of responding participants with relapse

SECONDARY outcome

Timeframe: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)

Population: All participants with PD-L1 CPS ≥10 who were included in a treatment group at randomization

Disease Control Rate (DCR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had 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) or Stable Disease for at least 24 weeks (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.\])

Outcome measures

Outcome measures
Measure	Pembrolizumab n=96 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=98 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥10	19.8 Percentage of participants Interval 12.4 to 29.2	17.3 Percentage of participants Interval 10.4 to 26.3

SECONDARY outcome

Timeframe: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)

Population: All participants with PD-L1 CPS ≥1 who were included in a treatment group at randomization

Outcome measures

Outcome measures
Measure	Pembrolizumab n=203 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=202 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1	14.3 Percentage of participants Interval 9.8 to 19.9	15.8 Percentage of participants Interval 11.1 to 21.6

SECONDARY outcome

Timeframe: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)

Population: All participants who were included in a treatment group at randomization

Outcome measures

Outcome measures
Measure	Pembrolizumab n=312 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=310 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Disease Control Rate Per RECIST 1.1 in All Participants	12.2 Percentage of participants Interval 8.8 to 16.3	18.7 Percentage of participants Interval 14.5 to 23.5

SECONDARY outcome

Timeframe: Up to approximately 60 months

Population: All randomized participants who received at least 1 dose of study treatment

An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=309 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=292 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Number of Participants Who Experienced One or More Adverse Events	285 Participants	281 Participants

SECONDARY outcome

Timeframe: Up to approximately 60 months

Population: All randomized participants who received at least 1 dose of study treatment

Outcome measures

Outcome measures
Measure	Pembrolizumab n=309 Participants Participants received pembrolizumab 200 mg IV every Q3W for up to 35 administrations (up to \~2 years).	Chemotherapy n=292 Participants Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines.
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event	14 Participants	16 Participants

Adverse Events

Pembrolizumab First Course

Serious events: 65 serious events

Other events: 259 other events

Deaths: 283 deaths

Chemotherapy

Serious events: 60 serious events

Other events: 263 other events

Deaths: 289 deaths

Pembrolizumab Second Course

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER