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)-China Extension Study

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04924062

Collaborator

(none)

160

Enrollment

Locations

Arms

41.7

Anticipated Duration (Months)

7.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In this China Extension study, pembrolizumab plus gemcitabine/cisplatin will be compared with placebo plus gemcitabine/cisplatin as first-line therapy in Chinese adults with advanced and/or unresectable biliary tract carcinoma. The primary hypothesis is pembrolizumab plus gemcitabine/cisplatin is superior to placebo plus gemcitabine/cisplatin with respect to overall survival (OS).

Condition or Disease	Intervention/Treatment	Phase
Biliary Tract Carcinoma	Biological: Pembrolizumab Drug: Gemcitabine Drug: Cisplatin Drug: Placebo	Phase 3

Detailed Description

The China extension study will include participants previously enrolled in China in the global study for MK-3475-966 (NCT04003636) plus those enrolled during the China extension enrollment period. A total of approximately 158 Chinese participants will be enrolled.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official 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

Actual Study Start Date :

Jul 10, 2020

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
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.	Biological: Pembrolizumab Pembrolizumab by intravenous (IV) infusion Other Names: MK-3475 Drug: Gemcitabine Gemcitabine by IV infusion Other Names: Gemzar Drug: Cisplatin Cisplatin by IV infusion Other Names: Platinol® Platinol®-AQ
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.	Drug: Gemcitabine Gemcitabine by IV infusion Other Names: Gemzar Drug: Cisplatin Cisplatin by IV infusion Other Names: Platinol® Platinol®-AQ Drug: Placebo Placebo to pembrolizumab

Arm

Intervention/Treatment

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.

Biological: Pembrolizumab

Pembrolizumab by intravenous (IV) infusion

Other Names:

MK-3475

Drug: Gemcitabine

Gemcitabine by IV infusion

Other Names:

Gemzar

Drug: Cisplatin

Cisplatin by IV infusion

Other Names:

Platinol®

Platinol®-AQ

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.

Drug: Gemcitabine

Gemcitabine by IV infusion

Other Names:

Gemzar

Drug: Cisplatin

Cisplatin by IV infusion

Other Names:

Platinol®

Platinol®-AQ

Drug: Placebo

Placebo to pembrolizumab

Outcome Measures

Primary Outcome Measures

Overall Survival (OS) [Up to approximately 38 months]
Overall survival is defined as the time from randomization to death due to any cause.

Secondary Outcome Measures

Progression-free Survival (PFS) per RECIST 1.1 as Assessed by BICR [Up to approximately 26 months]
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.
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [Up to approximately 26 months]
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 adjusted for this study to allow a maximum of 10 target lesions in total and 5 per organ.
Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR [Up to approximately 38 months]
For participants who demonstrate a 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.
Number of Participants Who Experience One or More Adverse Events (AE) [Up to approximately 38 months]
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.
Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE) [Up to approximately 38 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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)
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 coinhibitory 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anhui Provincial Hospital ( Site 0140)	Hefei	Anhui	China	230001
2	Beijing Cancer Hospital ( Site 0138)	Beijing	Beijing	China	100036
3	Peking Union Medical College Hospital ( Site 0150)	Beijing	Beijing	China	100730
4	First Affiliated Hospital of The Third Military Medical University ( Site 0130)	Chongqing	Chongqing	China	400038
5	Fujian Provincial Cancer Hospital ( Site 0154)	Fuzhou	Fujian	China	350014
6	900 Hospital of the Joint ( Site 0137)	Fuzhou	Fujian	China	350025
7	Guangdong Provincial People s Hospital ( Site 0161)	Guangzhou	Guangdong	China	510080
8	Harbin Medical University Cancer Hospital ( Site 0133)	Harbin	Heilongjiang	China	610000
9	Hunan Provincial People Hospital ( Site 0142)	Changsha	Hunan	China	410005
10	Hunan Cancer Hospital ( Site 0132)	Changsha	Hunan	China	410013
11	The Third Xiangya Hospital of Central South University ( Site 0157)	Changsha	Hunan	China	410013
12	The 81st Hospital of PLA ( Site 0128)	Nanjing	Jiangsu	China	210031
13	The First Hospital of Jilin University ( Site 0131)	Chanchun	Jilin	China	130021
14	Zhongshan Hospital Fudan University ( Site 0129)	Shanghai	Shanghai	China	200032
15	Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0158)	Shanghai	Shanghai	China	200127
16	Fudan University Shanghai Cancer Center ( Site 0160)	Shanghai	Shanghai	China	201315
17	Tangdu Hospital ( Site 0146)	XI An	Shanxi	China	710038
18	The First Affiliated Hospital of Xi an Jiaotong University ( Site 0145)	XI An	Shanxi	China	710048
19	West China Hospital of Sichuan University ( Site 0147)	Chengdu	Sichuan	China	610041
20	Tianjin Medical University Cancer Institute & Hospital ( Site 0155)	Tianjin	Tianjin	China	300060
21	The First Affiliated Hospital Zhejiang University ( Site 0136)	Hangzhou	Zhejiang	China	310003
22	Zhejiang Cancer Hospital ( Site 0134)	Hangzhou	Zhejiang	China	310022