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CompletedNCT01848834Updated Jun 28, 2021Results posted

Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-012/KEYNOTE-012)

A Phase 1 interventional study of Pembrolizumab in Cancer and Solid Tumor, sponsored by Merck Sharp & Dohme LLC. Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-06-28.

Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
297
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

This study is being done to investigate the safety, tolerability and anti-tumor activity of pembrolizumab (MK-3475) in participants with advanced triple negative breast cancer (TNBC) (Cohort A), advanced head and neck cancer (Cohorts B and B2), advanced urothelial cancer (Cohort C), or advanced gastric cancer (Cohort D). Additionally, for Cohort D, data is presented for Asian Pacific (AP) participants. Only participants with programmed cell death-ligand 1 (PD-L1) expressing tumors were enrolled in Cohorts A, B, C and D. Participants in Cohort B2 were enrolled irrespective of PD-L1 status.

The primary study hypothesis is that pembrolizumab is safe and well-tolerated.

Read the detailed description

Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (approximately up to 2 years) for reasons other than disease progression or intolerability, may be eligible for a second course of pembrolizumab for up to approximately 1 additional year at the investigator's discretion. Per protocol, response during this second course will not count towards the efficacy outcome measures and adverse events during this second course will not count towards the safety outcome measures.

Protocol Amendment 01 (08 Aug 2013) included a new study arm (Cohort D) for approximately 32 participants with advanced gastric cancer. Of these 32 participants, 16 will be from sites in the Asia Pacific (AP) region and the other 16 will be from sites outside the AP region.

Protocol Amendment 02 (07 Apr 2014) added a new study arm (Cohort B2) for approximately 110 participants with advanced head and neck cancer who will receive a lower dose of pembrolizumab every three weeks (Q3W). Both programmed cell death ligand 1 (PD-L1)- positive and PD-L1-negative participants will be enrolled into this cohort.

Protocol Amendment 03 (26 May 2015) removed the secondary objective of investigating the relationship between programmed cell death 1 (PD-1) inhibition and up-regulation of cytokines biomarkers predicting response (e.g. Interleukin-10 [IL-10]) from the protocol.

Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.

With Amendment 05 (11 Dec 2017), once study participants have achieved the study objective or the study has ended, participants will be discontinued from this study and enrolled in an extension study (KEYNOTE-587; NCT03486873) to continue protocol-defined assessments and treatment.

02

Conditions studied

  • Cancer
  • Solid Tumor

Browse trials for

Keywords

  • PD-1
  • PD1
  • PD-L1
  • PDL1
03

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 297 is above the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Browse Neoplasms studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Histologically or cytologically-confirmed diagnosis of tumor that is recurrent, metastatic, or persistent:

    • For Cohort A - triple negative breast cancer (estrogen, progesterone, and human epidermal growth factor receptor 2 [HER2] negative)
    • For Cohort B - squamous cell carcinoma of the head and neck (including human papilloma virus (HPV)-positive head and neck squamous cell cancer).
    • For Cohort C - urothelial tract cancer of the renal pelvis, ureter, bladder, or urethra (transitional cell or non-transitional cell histology)
    • For Cohort D - adenocarcinoma of the stomach or gastroesophageal junction
    • For Cohort B2 - squamous cell carcinoma of the head and neck (both HPV-positive and -negative head and neck squamous cell cancer)
  • Any number of prior treatment regimens
  • Measurable disease
  • Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
  • Female participants of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment
  • Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study treatment

Exclusion criteria

Exclusion Criteria:

  • Currently participating in/has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment
  • Diagnosis of immunosuppression or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
  • Anti-cancer monoclonal antibody treatment within 4 weeks prior to study Day 1 or not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent
  • Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Active autoimmune disease requiring systemic treatment within the past 3 months or documented history of clinically severe autoimmune disease, or syndrome that requires systemic steroids or immunosuppressive agents
  • Evidence of interstitial lung disease
  • Active infection requiring systemic therapy
  • Known psychiatric or substance abuse disorders
  • Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-L1, anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody
  • Known history of human immunodeficiency virus (HIV)
  • Known active Hepatitis B or Hepatitis C
  • Received live vaccine within 30 days prior to start of study treatment
  • Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is Investigational site or Sponsor staff directly involved with this trial, unless prospective Independent Review Board (IRB) approval (by Chair or Designee) is given allowing exception to this criterion for a specific participant
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
297 participants (actual)

Study arms

  • Experimental
    Cohort A: Triple Negative Breast Cancer

    Participants receive pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and continue to receive drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years).

    Biological: Pembrolizumab

  • Experimental
    Cohort B: Head & Neck Cancer

    Participants receive pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continue to receive drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years).

    Biological: Pembrolizumab

  • Experimental
    Cohort C: Urothelial Cancer

    Participants receive pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continue to receive drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years).

    Biological: Pembrolizumab

  • Experimental
    Cohort D: Gastric Cancer

    Participants receive pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continue to receive drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years).

    Biological: Pembrolizumab

  • Experimental
    Cohort B2: Head & Neck Cancer Expansion

    Participants receive pembrolizumab, 200 mg, IV once every 3 weeks, and continue to receive drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years).

    Biological: Pembrolizumab

Interventions

  • BiologicalPembrolizumab

    IV infusion

    Also known as: MK-3475, SCH 900475, KEYTRUDA®

06

What researchers measure

Primary outcomes

  1. Number of Participants Experiencing Adverse Events (AEs)

    An AE was defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE was presented for the first course pembrolizumab treatment per protocol.

    Time frame: Serious AEs: Up to 90 days after last dose of treatment (Up to 28 months); nonserious AEs: Up to 30 days after last dose of treatment (Up to 26 months) - through final analysis (FA) cutoff date 26 Apr 2016 (Cohorts: A, B, B2, D) & 01 Sep 2015 (Cohort C)

  2. Number of Participants Discontinuing From Study Treatment Due to an AE

    An AE was defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. Some cases of clinical progression that led to discontinuation of study treatment were captured as AEs that led to discontinuation of study treatment. The number of participants who discontinued study treatment due to an AE was presented for the first course pembrolizumab treatment per protocol.

    Time frame: Up to last dose of study treatment (Up to approximately 25 months) - through FA cutoff date 26 Apr 2016 (Cohorts: A, B, B2, D) & 01 Sep 2015 (Cohort C)

  3. Overall Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Response Rate Based on Blinded Independent Central Radiology (BICR) Review (Cohorts A, B, C, and D)

    Overall Response Rate (ORR) was defined as the percentage of participants who experienced a 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) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who experienced a CR or PR for Cohorts A, B, C and D participants was presented for the first course of pembrolizumab treatment per protocol. Cohorts A, B, C and D enrolled participants with programmed cell death-ligand 1 (PD-L1) positive tumors.

    Time frame: Every 8 weeks until disease progression (Cohorts A, B, D: Up to ~ 35 months; Cohort C: Up to ~ 28 months) - through FA cutoff date 26 Apr 2016 (Cohorts: A, B, D) & 01 Sep 2015 (Cohort C)

  4. Overall RECIST 1.1 Response Rate Based on BICR Review for Participants in Cohort B2

    ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who experienced a CR or PR in Cohort B2 was presented for the first course of pembrolizumab treatment per protocol.

    Time frame: Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016

Secondary outcomes

  1. Overall RECIST 1.1 Response Rate Based on BICR Review, Cohorts B and B2 Human Papilloma Virus (HPV)-Positive Participants

    ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who had tumors which were HPV positive and who experienced a CR or PR in the combined Cohorts B2 and B2 was presented for the first course of pembrolizumab treatment per protocol.

    Time frame: Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016

  2. Overall RECIST 1.1 Response Rate Based on BICR Review, Cohort D Asia-Pacific (AP) Participants

    ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who were from the Asia Pacific region and experienced a CR or PR in Cohort D was presented for the first course of pembrolizumab treatment per protocol.

    Time frame: Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016

  3. Overall RECIST 1.1 Response Rate Based on BICR Review, for Participants Previously Treated With Cetuximab and Platinum in Cohorts B and B2

    ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who were previously treated with cetuximab and platinum and experienced a CR or PR in the Cohorts B and B2 was presented for the first course of pembrolizumab treatment per protocol.

    Time frame: Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016

  4. Overall RECIST 1.1 Response Rate Based on Investigator Assessment for Cohorts A, B, C and D

    ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed by Investigator evaluation. The percentage of participants who experienced a CR or PR in Cohorts A, B, C and D based on investigator assessment was presented for the first course of pembrolizumab treatment per protocol. ORR per RECIST 1.1 based on investigator assessment was presented for Cohort B2 in a separate outcome measure.

    Time frame: Every 8 weeks until disease progression (Cohorts A, B, D: Up to ~ 35 months; Cohort C: Up to ~ 28 months) - through FA cutoff date 26 Apr 2016 (Cohorts: A, B, D) & 01 Sep 2015 (Cohort C)

  5. Overall RECIST 1.1 Response Rate Based on Investigator Assessment for Cohort B2

    ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed by Investigator evaluation. The percentage of participants who experienced a CR or PR in Cohort B2 based on investigator assessment was presented for the first course of pembrolizumab treatment per protocol. ORR per RECIST 1.1 based on investigator assessment was presented for the other cohorts in a separate outcome measure.

    Time frame: Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016

Other outcomes

  1. Number of Participants With Log Fold Change From Baseline in Cytokines (Interleukin 10 [IL-10]) >1

    IL-10 is an anti-inflammatory cytokine. The number of participants with a log fold change from Baseline in IL-10 \>1 was to be presented. Protocol Amendment 03 (26 May 2015) removed the secondary objective of investigating the relationship between programmed cell death 1 (PD-1) inhibition and up-regulation of cytokines biomarkers predicting response (e.g. IL-10) from the protocol. No data were collected for this outcome measure.

    Time frame: Baseline and Week 8

07

Results

Posted Jun 26, 2017

Participant flow

Participant flow — Overall Study
MilestoneCohort A: Triple Negative Breast CancerCohort B: Head & Neck CancerCohort C: Urothelial CancerCohort D: Gastric CancerCohort B2: Head & Neck Cancer Expansion
Started32613339132
Treated32603339132
Completed131391338
Not completed1948242694
Withdrew: Adverse event311359
Withdrew: Death2111827
Withdrew: Excluded medication54366
Withdrew: Lost to follow-up55303
Withdrew: Physician decision134011
Withdrew: Protocol violation00001
Withdrew: Sponsor decision11011
Withdrew: Withdrawal by subject21310636

Outcome measures

PrimaryNumber of Participants Experiencing Adverse Events (AEs)

An AE was defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE was presented for the first course pembrolizumab treatment per protocol.

Time frame:
Serious AEs: Up to 90 days after last dose of treatment (Up to 28 months); nonserious AEs: Up to 30 days after last dose of treatment (Up to 26 months) - through final analysis (FA) cutoff date 26 Apr 2016 (Cohorts: A, B, B2, D) & 01 Sep 2015 (Cohort C)
Reported as:
Count of participants · Participants
Number of Participants Experiencing Adverse Events (AEs)
ParticipantsCohort A: Triple Negative Breast CancerCohort B: Head & Neck CancerCohort C: Urothelial CancerCohort D: Gastric CancerCohort B2: Head & Neck Cancer Expansion
Number of Participants Experiencing Adverse Events (AEs)32583339130
PrimaryNumber of Participants Discontinuing From Study Treatment Due to an AE

An AE was defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. Some cases of clinical progression that led to discontinuation of study treatment were captured as AEs that led to discontinuation of study treatment. The number of participants who discontinued study treatment due to an AE was presented for the first course pembrolizumab treatment per protocol.

Time frame:
Up to last dose of study treatment (Up to approximately 25 months) - through FA cutoff date 26 Apr 2016 (Cohorts: A, B, B2, D) & 01 Sep 2015 (Cohort C)
Reported as:
Count of participants · Participants
Number of Participants Discontinuing From Study Treatment Due to an AE
ParticipantsCohort A: Triple Negative Breast CancerCohort B: Head & Neck CancerCohort C: Urothelial CancerCohort D: Gastric CancerCohort B2: Head & Neck Cancer Expansion
Number of Participants Discontinuing From Study Treatment Due to an AE6128221
PrimaryOverall Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Response Rate Based on Blinded Independent Central Radiology (BICR) Review (Cohorts A, B, C, and D)

Overall Response Rate (ORR) was defined as the percentage of participants who experienced a 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) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who experienced a CR or PR for Cohorts A, B, C and D participants was presented for the first course of pembrolizumab treatment per protocol. Cohorts A, B, C and D enrolled participants with programmed cell death-ligand 1 (PD-L1) positive tumors.

Time frame:
Every 8 weeks until disease progression (Cohorts A, B, D: Up to ~ 35 months; Cohort C: Up to ~ 28 months) - through FA cutoff date 26 Apr 2016 (Cohorts: A, B, D) & 01 Sep 2015 (Cohort C)
Reported as:
Number · Percentage of Participants
Overall Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Response Rate Based on Blinded Independent Central Radiology (BICR) Review (Cohorts A, B, C, and D)
Percentage of ParticipantsCohort A: Triple Negative Breast CancerCohort B: Head & Neck CancerCohort C: Urothelial CancerCohort D: Gastric Cancer
Overall Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Response Rate Based on Blinded Independent Central Radiology (BICR) Review (Cohorts A, B, C, and D)15.6 (5.3 to 32.8)16.7 (8.3 to 28.5)21.2 (9.0 to 38.9)20.5 (9.3 to 36.5)
PrimaryOverall RECIST 1.1 Response Rate Based on BICR Review for Participants in Cohort B2

ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who experienced a CR or PR in Cohort B2 was presented for the first course of pembrolizumab treatment per protocol.

Time frame:
Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016
Reported as:
Number · Percentage of Participants
Overall RECIST 1.1 Response Rate Based on BICR Review for Participants in Cohort B2
Percentage of ParticipantsCohort B2: Head & Neck Cancer Expansion
Overall RECIST 1.1 Response Rate Based on BICR Review for Participants in Cohort B218.2 (12.0 to 25.8)
SecondaryOverall RECIST 1.1 Response Rate Based on BICR Review, Cohorts B and B2 Human Papilloma Virus (HPV)-Positive Participants

ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who had tumors which were HPV positive and who experienced a CR or PR in the combined Cohorts B2 and B2 was presented for the first course of pembrolizumab treatment per protocol.

Time frame:
Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016
Reported as:
Number · Percentage of Participants
Overall RECIST 1.1 Response Rate Based on BICR Review, Cohorts B and B2 Human Papilloma Virus (HPV)-Positive Participants
Percentage of ParticipantsCohorts B & B2: Head & Neck Cancer HPV-Positive Participants
Overall RECIST 1.1 Response Rate Based on BICR Review, Cohorts B and B2 Human Papilloma Virus (HPV)-Positive Participants21.9 (12.5 to 34.0)
SecondaryOverall RECIST 1.1 Response Rate Based on BICR Review, Cohort D Asia-Pacific (AP) Participants

ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who were from the Asia Pacific region and experienced a CR or PR in Cohort D was presented for the first course of pembrolizumab treatment per protocol.

Time frame:
Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016
Reported as:
Number · Percentage of Participants
Overall RECIST 1.1 Response Rate Based on BICR Review, Cohort D Asia-Pacific (AP) Participants
Percentage of ParticipantsCohort D: Gastric Cancer AP Participants
Overall RECIST 1.1 Response Rate Based on BICR Review, Cohort D Asia-Pacific (AP) Participants21.1 (6.1 to 45.6)
SecondaryOverall RECIST 1.1 Response Rate Based on BICR Review, for Participants Previously Treated With Cetuximab and Platinum in Cohorts B and B2

ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who were previously treated with cetuximab and platinum and experienced a CR or PR in the Cohorts B and B2 was presented for the first course of pembrolizumab treatment per protocol.

Time frame:
Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016
Reported as:
Number · Percentage of Participants
Overall RECIST 1.1 Response Rate Based on BICR Review, for Participants Previously Treated With Cetuximab and Platinum in Cohorts B and B2
Percentage of ParticipantsCohorts B & B2: Head & Neck Cancer
Overall RECIST 1.1 Response Rate Based on BICR Review, for Participants Previously Treated With Cetuximab and Platinum in Cohorts B and B214.5 (8.5 to 22.5)
SecondaryOverall RECIST 1.1 Response Rate Based on Investigator Assessment for Cohorts A, B, C and D

ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed by Investigator evaluation. The percentage of participants who experienced a CR or PR in Cohorts A, B, C and D based on investigator assessment was presented for the first course of pembrolizumab treatment per protocol. ORR per RECIST 1.1 based on investigator assessment was presented for Cohort B2 in a separate outcome measure.

Time frame:
Every 8 weeks until disease progression (Cohorts A, B, D: Up to ~ 35 months; Cohort C: Up to ~ 28 months) - through FA cutoff date 26 Apr 2016 (Cohorts: A, B, D) & 01 Sep 2015 (Cohort C)
Reported as:
Number · Percentage of Participants
Overall RECIST 1.1 Response Rate Based on Investigator Assessment for Cohorts A, B, C and D
Percentage of ParticipantsCohort A: Triple Negative Breast CancerCohort B: Head & Neck CancerCohort C: Urothelial CancerCohort D: Gastric Cancer
Overall RECIST 1.1 Response Rate Based on Investigator Assessment for Cohorts A, B, C and D15.6 (5.3 to 32.8)16.7 (8.3 to 28.5)21.2 (9.0 to 38.9)33.3 (19.1 to 50.2)
SecondaryOverall RECIST 1.1 Response Rate Based on Investigator Assessment for Cohort B2

ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed by Investigator evaluation. The percentage of participants who experienced a CR or PR in Cohort B2 based on investigator assessment was presented for the first course of pembrolizumab treatment per protocol. ORR per RECIST 1.1 based on investigator assessment was presented for the other cohorts in a separate outcome measure.

Time frame:
Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016
Reported as:
Number · Percentage of Participants
Overall RECIST 1.1 Response Rate Based on Investigator Assessment for Cohort B2
Percentage of ParticipantsCohort B2: Head & Neck Cancer Expansion
Overall RECIST 1.1 Response Rate Based on Investigator Assessment for Cohort B220.5 (13.9 to 28.3)
Other pre-specifiedNumber of Participants With Log Fold Change From Baseline in Cytokines (Interleukin 10 [IL-10]) >1

IL-10 is an anti-inflammatory cytokine. The number of participants with a log fold change from Baseline in IL-10 \>1 was to be presented. Protocol Amendment 03 (26 May 2015) removed the secondary objective of investigating the relationship between programmed cell death 1 (PD-1) inhibition and up-regulation of cytokines biomarkers predicting response (e.g. IL-10) from the protocol. No data were collected for this outcome measure.

Time frame:
Baseline and Week 8

No measurements were reported for this outcome.

Adverse events

Collected over Serious and non-serious AEs were collected up to ~ 71 months and all-cause mortality up to ~ 85 months for pembrolizumab first and second course treatment (through end of trial (EOT) cutoff date 30 June 2020).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort A: Triple Negative Breast Cancer25/32 (78.1%)13/32 (40.6%)31/32 (96.9%)
Cohort B: Head & Neck Cancer54/61 (88.5%)27/60 (45%)58/60 (96.7%)
Cohort C: Urothelial Cancer29/33 (87.9%)21/33 (63.6%)32/33 (97%)
Cohort D: Gastric Cancer34/39 (87.2%)17/39 (43.6%)37/39 (94.9%)
Cohort B2: Head & Neck Cancer Expansion110/132 (83.3%)60/132 (45.5%)124/132 (93.9%)
Most frequent serious events
Showing 10 of 158
Most frequent serious events
EventCohort A: Triple Negative Breast CancerCohort B: Head & Neck CancerCohort C: Urothelial CancerCohort D: Gastric CancerCohort B2: Head & Neck Cancer Expansion
Urinary tract infectionInfections and infestations0/321/603/330/390/132
PneumoniaInfections and infestations0/325/601/331/393/132
Respiratory failureRespiratory, thoracic and mediastinal disorders0/324/600/330/390/132
Back painMusculoskeletal and connective tissue disorders2/320/600/330/391/132
HeadacheNervous system disorders2/320/600/330/390/132
SepsisInfections and infestations0/321/602/330/391/132
MyositisMusculoskeletal and connective tissue disorders0/320/602/330/390/132
Abdominal painGastrointestinal disorders0/321/600/332/391/132
Upper gastrointestinal haemorrhageGastrointestinal disorders0/320/600/332/391/132
CellulitisInfections and infestations0/323/600/330/390/132
Most frequent other events
Showing 10 of 105
Most frequent other events
EventCohort A: Triple Negative Breast CancerCohort B: Head & Neck CancerCohort C: Urothelial CancerCohort D: Gastric CancerCohort B2: Head & Neck Cancer Expansion
FatigueGeneral disorders17/3232/6017/3312/3959/132
Decreased appetiteMetabolism and nutrition disorders2/3214/6013/3312/3930/132
Abdominal painGastrointestinal disorders2/323/606/3313/398/132
Oedema peripheralGeneral disorders2/327/6011/334/397/132
AnaemiaBlood and lymphatic system disorders3/3219/607/334/3927/132
MyalgiaMusculoskeletal and connective tissue disorders10/328/603/333/397/132
ConstipationGastrointestinal disorders6/3215/6010/337/3921/132
NauseaGastrointestinal disorders9/3215/609/3311/3920/132
DiarrhoeaGastrointestinal disorders9/3213/603/335/3914/132
PyrexiaGeneral disorders3/3212/609/334/3922/132

Baseline characteristics

The baseline analysis population consisted of all allocated participants.

Age, Continuous
Age, Continuous(Years)Cohort A: Triple Negative Breast CancerCohort B: Head & Neck CancerCohort C: Urothelial CancerCohort D: Gastric CancerCohort B2: Head & Neck Cancer ExpansionTotal
Mean51.9 ± 12.161.5 ± 11.568.5 ± 10.358.3 ± 13.258.9 ± 9.759.7 ± 11.6
Sex: Female, Male
Sex: Female, Male(Participants)Cohort A: Triple Negative Breast CancerCohort B: Head & Neck CancerCohort C: Urothelial CancerCohort D: Gastric CancerCohort B2: Head & Neck Cancer ExpansionTotal
Female321210112287
Male0492328110210
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Cohort A: Triple Negative Breast CancerCohort B: Head & Neck CancerCohort C: Urothelial CancerCohort D: Gastric CancerCohort B2: Head & Neck Cancer ExpansionTotal
Hispanic or Latino2111712
Not Hispanic or Latino29582337108255
Unknown or Not Reported12911730
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cohort A: Triple Negative Breast CancerCohort B: Head & Neck CancerCohort C: Urothelial CancerCohort D: Gastric CancerCohort B2: Head & Neck Cancer ExpansionTotal
American Indian or Alaska Native000112
Asian010192848
Native Hawaiian or Other Pacific Islander000000
Black or African American7620419
White2553311995223
More than one race010012
Unknown or Not Reported000033
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Study locations

No study locations are listed for this record.

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References and documents

Publications

  • Muro K, Chung HC, Shankaran V, Geva R, Catenacci D, Gupta S, Eder JP, Golan T, Le DT, Burtness B, McRee AJ, Lin CC, Pathiraja K, Lunceford J, Emancipator K, Juco J, Koshiji M, Bang YJ. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol. 2016 Jun;17(6):717-726. doi: 10.1016/S1470-2045(16)00175-3. Epub 2016 May 3. PubMed 27157491 ↗
  • Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol. 2016 Jul 20;34(21):2460-7. doi: 10.1200/JCO.2015.64.8931. Epub 2016 May 2. PubMed 27138582 ↗
  • Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C, Cheng JD, Chow LQ. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 2016 Jul;17(7):956-965. doi: 10.1016/S1470-2045(16)30066-3. Epub 2016 May 27. PubMed 27247226 ↗
  • Plimack ER, Bellmunt J, Gupta S, Berger R, Chow LQ, Juco J, Lunceford J, Saraf S, Perini RF, O'Donnell PH. Safety and activity of pembrolizumab in patients with locally advanced or metastatic urothelial cancer (KEYNOTE-012): a non-randomised, open-label, phase 1b study. Lancet Oncol. 2017 Feb;18(2):212-220. doi: 10.1016/S1470-2045(17)30007-4. Epub 2017 Jan 10. PubMed 28081914 ↗
  • Chow LQM, Haddad R, Gupta S, Mahipal A, Mehra R, Tahara M, Berger R, Eder JP, Burtness B, Lee SH, Keam B, Kang H, Muro K, Weiss J, Geva R, Lin CC, Chung HC, Meister A, Dolled-Filhart M, Pathiraja K, Cheng JD, Seiwert TY. Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort. J Clin Oncol. 2016 Nov 10;34(32):3838-3845. doi: 10.1200/JCO.2016.68.1478. Epub 2016 Sep 30. PubMed 27646946 ↗
  • Haddad RI, Seiwert TY, Chow LQM, Gupta S, Weiss J, Gluck I, Eder JP, Burtness B, Tahara M, Keam B, Kang H, Muro K, Albright A, Mogg R, Ayers M, Huang L, Lunceford J, Cristescu R, Cheng J, Mehra R. Influence of tumor mutational burden, inflammatory gene expression profile, and PD-L1 expression on response to pembrolizumab in head and neck squamous cell carcinoma. J Immunother Cancer. 2022 Feb;10(2):e003026. doi: 10.1136/jitc-2021-003026. PubMed 35217573 ↗
  • Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091. PubMed 35101941 ↗
  • van Vugt MJH, Stone JA, De Greef RHJMM, Snyder ES, Lipka L, Turner DC, Chain A, Lala M, Li M, Robey SH, Kondic AG, De Alwis D, Mayawala K, Jain L, Freshwater T. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019 Aug 8;7(1):212. doi: 10.1186/s40425-019-0663-4. PubMed 31395089 ↗
  • Tahara M, Muro K, Hasegawa Y, Chung HC, Lin CC, Keam B, Takahashi K, Cheng JD, Bang YJ. Pembrolizumab in Asia-Pacific patients with advanced head and neck squamous cell carcinoma: Analyses from KEYNOTE-012. Cancer Sci. 2018 Mar;109(3):771-776. doi: 10.1111/cas.13480. Epub 2018 Feb 8. PubMed 29284202 ↗

Study documents

  • Protocol and statistical analysis plan · Dec 11, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 28, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT01848834
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
May 8, 2013
Start date
May 7, 2013
Primary completion
Apr 26, 2016
Completion
Jun 30, 2020
Results posted
Jun 26, 2017
Last update
Jun 28, 2021

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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