Clinical Trials /

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)

NCT04003636

Description:

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).

Related Conditions:
  • Extrahepatic Cholangiocarcinoma
  • Gallbladder Carcinoma
  • Intrahepatic Cholangiocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief 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)
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 3475-966
  • SECONDARY ID: 2019-000944-82
  • SECONDARY ID: MK-3475-966
  • SECONDARY ID: KEYNOTE-966
  • SECONDARY ID: 195007
  • NCT ID: NCT04003636

Conditions

  • Biliary Tract Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabMK-3475Arm A (Pembrolizumab+Gemcitabine+Cisplatin)
GemcitabineGemzarArm A (Pembrolizumab+Gemcitabine+Cisplatin)
CisplatinPlatinol®, Platinol®-AQArm A (Pembrolizumab+Gemcitabine+Cisplatin)
PlaceboArm B (Placebo+Gemcitabine+Cisplatin)

Purpose

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 Arms

NameTypeDescriptionInterventions
Arm A (Pembrolizumab+Gemcitabine+Cisplatin)ExperimentalPembrolizumab, 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.
  • Pembrolizumab
  • Gemcitabine
  • Cisplatin
Arm B (Placebo+Gemcitabine+Cisplatin)Placebo ComparatorPlacebo 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.
  • Gemcitabine
  • Cisplatin
  • Placebo

Eligibility Criteria

        Inclusion Criteria

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

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

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

          4. Provide archival tumor tissue sample or newly obtained core or excisional biopsy of a
             tumor lesion.

          5. Have a life expectancy of greater than 3 months.

          6. Have adequate organ function.

        Exclusion Criteria

          1. 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.

          2. Has ampullary cancer.

          3. Has small cell cancer, neuroendocrine tumors, lymphoma, sarcoma and/or Mucinous cystic
             neoplasms.

          4. 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., CTLA-4, OX-40,
             CD137).

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

          6. Has had an allogenic tissue/solid organ transplant.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR)
Time Frame:Up to 48 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR
Time Frame:Up to 48 months
Safety Issue:
Description: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.
Measure:Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR
Time Frame:Up to 48 months
Safety Issue:
Description: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.
Measure:Number of Participants Who Experience One or More Adverse Events (AE)
Time Frame:Up to 48 months
Safety Issue:
Description: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.
Measure:Number of Participants Who Discontinued Study Intervention Due to an Adverse Event
Time Frame:Up to 48 months
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • programmed cell death 1 (PD-1)
  • Pembrolizumab
  • cholangiocarcinoma
  • gall bladder cancer
  • check point inhibitor
  • immunotherapy
  • Biliary
  • Keytruda
  • Bile Duct Cancer

Last Updated