Study of Pembrolizumab (MK-3475) in Participants With Adv... | NCT01848834

NCT01848834

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description
2012-005771-14	EudraCT Number
142453	Registry Identifier	JAPIC_CTI
MK-3475-012	Other Identifier	Merck

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort A: Triple Negative Breast Cancer	Experimental	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
Cohort B: Head & Neck Cancer	Experimental	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
Cohort C: Urothelial Cancer	Experimental	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
Cohort D: Gastric Cancer	Experimental	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
Cohort B2: Head & Neck Cancer Expansion

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Biological	IV infusion	Cohort A: Triple Negative Breast Cancer Cohort B2: Head & Neck Cancer Expansion Cohort B: Head & Neck Cancer

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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)
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.	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)
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)

Secondary Outcomes

Measure	Description	Time Frame
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.

Other Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

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:

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

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

PubMed Identifier	Type	Citation	Retractions
27157491	Result	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.
27138582

Arm/Group Information

ID	Title	Description
FG000	Cohort A: Triple Negative Breast Cancer	Participants received pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). 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.
FG001	Cohort B: Head & Neck Cancer	Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). 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.
FG002	Cohort C: Urothelial Cancer	Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). 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.
FG003	Cohort D: Gastric Cancer	Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). 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.
FG004	Cohort B2: Head & Neck Cancer Expansion	Participants received pembrolizumab, 200 mg, IV once every 3 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). 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.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Cohort A: Triple Negative Breast Cancer	Participants received pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). 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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

The population consisted of all participants who received ≥1 dose of study treatment.

Posted

Count of Participants

Participants

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)

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort A: Triple Negative Breast Cancer	Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). 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.

OG000	Cohort A: Triple Negative Breast Cancer	Participants received pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). 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.
OG001	Cohort B: Head & Neck Cancer	Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). 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.
OG002	Cohort C: Urothelial Cancer	Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). 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.
OG003	Cohort D: Gastric Cancer	Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). 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.
OG004	Cohort B2: Head & Neck Cancer Expansion	Participants received pembrolizumab, 200 mg, IV once every 3 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). 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.