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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04003636




Registration number
NCT04003636
Ethics application status
Date submitted
28/06/2019
Date registered
1/07/2019
Date last updated
7/07/2020

Titles & IDs
Public title
Pembrolizumab (MK-3475) Plus Gemcitabine/Cisplatin Versus Placebo Plus Gemcitabine/Cisplatin for First-Line Advanced and/or Unresectable Biliary Tract Carcinoma (BTC) (MK-3475-966/KEYNOTE-966)
Scientific title
A Phase 3 Randomized, Double Blind Study of Pembrolizumab Plus Gemcitabine/Cisplatin Versus Placebo Plus Gemcitabine/Cisplatin as First-Line Therapy in Participants With Advanced and/or Unresectable Biliary Tract Carcinoma
Secondary ID [1] 0 0
2019-000944-82
Secondary ID [2] 0 0
3475-966
Universal Trial Number (UTN)
Trial acronym
KEYNOTE-966
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Biliary Tract Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Cisplatin
Treatment: Drugs - Placebo

Experimental: Arm A (Pembrolizumab+Gemcitabine+Cisplatin) - Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.

Placebo Comparator: Arm B (Placebo+Gemcitabine+Cisplatin) - Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.


Treatment: Drugs: Pembrolizumab
Pembrolizumab by intravenous (IV) infusion

Treatment: Drugs: Gemcitabine
Gemcitabine by IV infusion

Treatment: Drugs: Cisplatin
Cisplatin by IV infusion

Treatment: Drugs: Placebo
Placebo to pembrolizumab

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR) - Progression-free survival is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Progressive Disease (PD) is a =20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of =20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Timepoint [1] 0 0
Up to 48 months
Primary outcome [2] 0 0
Overall Survival (OS) - Overall survival is defined as the time from randomization to death due to any cause.
Timepoint [2] 0 0
Up to 48 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR - ORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: a =30% decrease in the sum of diameters [SOD] of target lesions) as assessed by BICR per RECIST 1.1, which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Timepoint [1] 0 0
Up to 48 months
Secondary outcome [2] 0 0
Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR - For participants who demonstrate confirmed CR or PR, DOR is the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. Complete Response is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response is a =30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is a =20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of =20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Timepoint [2] 0 0
Up to 48 months
Secondary outcome [3] 0 0
Number of Participants Who Experience One or More Adverse Events (AE) - An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Timepoint [3] 0 0
Up to 48 months
Secondary outcome [4] 0 0
Number of Participants Who Discontinued Study Intervention Due to an Adverse Event - An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Timepoint [4] 0 0
Up to 48 months

Eligibility
Key inclusion criteria
Inclusion Criteria

- Has histologically confirmed diagnosis of advanced (metastatic) and/or unresectable
(locally advanced) biliary tract cancer (intra-or extrahepatic cholangiocarcinoma or
gallbladder cancer)

- Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST
1.1), as determined by the site investigator

- Participants with a history of hepatitis B or hepatitis C can be enrolled if they meet
study criteria

- Is able to provide archival tumor tissue sample or newly obtained core or excisional
biopsy of a tumor lesion

- Has a life expectancy of greater than 3 months

- Has adequate organ function
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

- Has had previous systemic therapy for advanced (metastatic) or unresectable (locally
advanced) biliary tract cancer (intra-or extra hepatic cholangiocarcinoma or
gallbladder cancer), with the exception of adjuvant therapy which is allowed

- Has ampullary cancer

- Has small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology
and/or mucinous cystic neoplasms

- Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-
programmed cell death ligand 1 or 2 (anti-PD-L1, anti-PD-L2) agent or with an agent
directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic
T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)

- Has a known history of, or any evidence of, central nervous system (CNS) metastases
and/or carcinomatous meningitis, as assessed by local site investigator

- Has had an allogenic tissue/solid organ transplant

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital ( Site 0707) - Liverpool
Recruitment hospital [2] 0 0
Mid North Coast Cancer Institute ( Site 0708) - Port Macquarie
Recruitment hospital [3] 0 0
Gallipoli Medical Research Foundation ( Site 0705) - Brisbane
Recruitment hospital [4] 0 0
Western Health-Sunshine Hospital ( Site 0709) - St Albans
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [3] 0 0
4120 - Brisbane
Recruitment postcode(s) [4] 0 0
3021 - St Albans
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Oklahoma
Country [9] 0 0
United States of America
State/province [9] 0 0
Oregon
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
Belgium
State/province [12] 0 0
Bruxelles-Capitale, Region De
Country [13] 0 0
Belgium
State/province [13] 0 0
Hainaut
Country [14] 0 0
Belgium
State/province [14] 0 0
Oost-Vlaanderen
Country [15] 0 0
Belgium
State/province [15] 0 0
Vlaams-Brabant
Country [16] 0 0
Belgium
State/province [16] 0 0
Liege
Country [17] 0 0
Brazil
State/province [17] 0 0
Rio Grande Do Sul
Country [18] 0 0
Brazil
State/province [18] 0 0
Rio de Janeiro
Country [19] 0 0
Brazil
State/province [19] 0 0
Sao Paulo
Country [20] 0 0
Canada
State/province [20] 0 0
Alberta
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
Chile
State/province [23] 0 0
Araucania
Country [24] 0 0
Chile
State/province [24] 0 0
Coquimbo
Country [25] 0 0
Chile
State/province [25] 0 0
Libertador General Bernardo O'Higgins
Country [26] 0 0
Chile
State/province [26] 0 0
Region Metropolitana De Santiago
Country [27] 0 0
France
State/province [27] 0 0
Gironde
Country [28] 0 0
France
State/province [28] 0 0
Hauts-de-Seine
Country [29] 0 0
France
State/province [29] 0 0
Herault
Country [30] 0 0
France
State/province [30] 0 0
Ille-et-Vilaine
Country [31] 0 0
France
State/province [31] 0 0
Puy-de-Dome
Country [32] 0 0
France
State/province [32] 0 0
Val-de-Marne
Country [33] 0 0
Germany
State/province [33] 0 0
Hessen
Country [34] 0 0
Germany
State/province [34] 0 0
Nordrhein-Westfalen
Country [35] 0 0
Germany
State/province [35] 0 0
Berlin
Country [36] 0 0
Hong Kong
State/province [36] 0 0
Hong Kong
Country [37] 0 0
Ireland
State/province [37] 0 0
Dublin
Country [38] 0 0
Israel
State/province [38] 0 0
HaMerkaz
Country [39] 0 0
Israel
State/province [39] 0 0
Heifa
Country [40] 0 0
Israel
State/province [40] 0 0
Tell Abib
Country [41] 0 0
Israel
State/province [41] 0 0
Yerushalayim
Country [42] 0 0
Italy
State/province [42] 0 0
Roma
Country [43] 0 0
Italy
State/province [43] 0 0
Bologna
Country [44] 0 0
Italy
State/province [44] 0 0
Catania
Country [45] 0 0
Italy
State/province [45] 0 0
Milano
Country [46] 0 0
Italy
State/province [46] 0 0
Pisa
Country [47] 0 0
Italy
State/province [47] 0 0
Verona
Country [48] 0 0
Japan
State/province [48] 0 0
Aichi
Country [49] 0 0
Japan
State/province [49] 0 0
Kanagawa
Country [50] 0 0
Japan
State/province [50] 0 0
Osaka
Country [51] 0 0
Japan
State/province [51] 0 0
Fukuoka
Country [52] 0 0
Japan
State/province [52] 0 0
Kyoto
Country [53] 0 0
Japan
State/province [53] 0 0
Tokyo
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Gyeongsangbuk-do
Country [55] 0 0
Korea, Republic of
State/province [55] 0 0
Jeonranamdo
Country [56] 0 0
Korea, Republic of
State/province [56] 0 0
Kyonggi-do
Country [57] 0 0
Korea, Republic of
State/province [57] 0 0
Seoul-teukbyeolsi [Seoul]
Country [58] 0 0
Korea, Republic of
State/province [58] 0 0
Taejon-Kwangyokshi
Country [59] 0 0
Malaysia
State/province [59] 0 0
Johor
Country [60] 0 0
Malaysia
State/province [60] 0 0
Pulau Pinang
Country [61] 0 0
Malaysia
State/province [61] 0 0
Wilayah Persekutuan Kuala Lumpur
Country [62] 0 0
Malaysia
State/province [62] 0 0
Wilayah Persekutuan Putrajaya
Country [63] 0 0
Netherlands
State/province [63] 0 0
Limburg
Country [64] 0 0
Netherlands
State/province [64] 0 0
Noord-Holland
Country [65] 0 0
Netherlands
State/province [65] 0 0
Zuid-Holland
Country [66] 0 0
Netherlands
State/province [66] 0 0
Utrecht
Country [67] 0 0
New Zealand
State/province [67] 0 0
Auckland
Country [68] 0 0
Spain
State/province [68] 0 0
Asturias
Country [69] 0 0
Spain
State/province [69] 0 0
Barcelona [Barcelona]
Country [70] 0 0
Spain
State/province [70] 0 0
Madrid
Country [71] 0 0
Spain
State/province [71] 0 0
Malaga
Country [72] 0 0
Taiwan
State/province [72] 0 0
Taipei
Country [73] 0 0
Taiwan
State/province [73] 0 0
Kaohsiung
Country [74] 0 0
Taiwan
State/province [74] 0 0
Taichung
Country [75] 0 0
Taiwan
State/province [75] 0 0
Tainan
Country [76] 0 0
Taiwan
State/province [76] 0 0
Taoyuan
Country [77] 0 0
Thailand
State/province [77] 0 0
Krung Thep Maha Nakhon
Country [78] 0 0
Turkey
State/province [78] 0 0
Adana
Country [79] 0 0
Turkey
State/province [79] 0 0
Ankara
Country [80] 0 0
Turkey
State/province [80] 0 0
Istanbul
Country [81] 0 0
Turkey
State/province [81] 0 0
Izmir
Country [82] 0 0
Turkey
State/province [82] 0 0
Kayseri
Country [83] 0 0
Turkey
State/province [83] 0 0
Malatya

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a study of pembrolizumab plus gemcitabine/cisplatin versus placebo plus
gemcitabine/cisplatin as first-line therapy in participants with advanced and/or unresectable
biliary tract carcinoma. The study has 2 primary hypotheses: 1. Pembrolizumab plus
gemcitabine/cisplatin is superior to placebo plus gemcitabine/cisplatin with respect to
progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
by blinded independent central review (BICR) and 2. Pembrolizumab plus gemcitabine/cisplatin
is superior to placebo plus gemcitabine/cisplatin with respect to overall survival (OS).
Trial website
https://clinicaltrials.gov/show/NCT04003636
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04003636