Advanced and/or Unresectable Biliary Tract Carcinoma (Intrahepatic, Extrahepatic, or Gallbladder) MedDRA version: 20.0 Level: LLT Classification code 10004655 Term: Biliary carcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Keytruda (pembrolizumab, MK-3475)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration unit: m
Sponsors
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion 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. Has measurable disease based on RECIST 1.1, as determined by the site investigator. Lesions situated in a previously treated area by either radiotherapy, photodynamic therapy, or arterial embolization are considered measurable if progression has been shown in such lesions and they meet criteria for measurable disease per RECIST 1.1. 3. Participants with past or ongoing HCV infection are eligible for the study. Treated participants must have completed their treatment at least 1 month prior to starting study intervention. Untreated or incompletely treated HCV participants may initiate antiviral therapy for HCV if liver function remains stable for at least 3 months on study intervention. 4. Participants with controlled hepatitis B are eligible for the study , as long as they meet the following criteria: - Participants with chronic HBV infection, defined as HBsAg positive and/or detectable HBV DNA, must be given antiviral therapy for HBV for at least 4 weeks prior to the first dose of study intervention and HBV viral load must be less than 100 IU/mL prior to first dose of study intervention. Participants on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study intervention. Antiviral therapy after completion of study intervention should follow local guidelines. - Participants with clinically resolved HBV infection, defined as HBsAg negative and anti-HBc positive, and who have an undetectable HBV viral load at screening should be checked every 6 weeks for HBV viral load and treated for HBV if viral load is over 100 IU/mL. Antiviral therapy after completion of study intervention should follow local guidelines. 5. Is male or female, from at least 18 years of age inclusive, at the time of signing the informed consent. 6. Male participants are eligible to participate if they agree to the following during the intervention period and for at least and through 180 days after the last dose of chemotherapy: • Refrain from donating sperm, PLUS either: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR • Must agree to use contraception unless confirmed to be azoospermic. • Male participants must also agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex. 7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: - Is not a woman of childbearing potential (WOCBP) OR - Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), as described in the Protocol - A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, as required by local regulations) within 24 hours (urine) or 72 hours (serum) before the first dose of study intervention. - If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pr
Exclusion criteria
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 neoadjuvant/adjuvant therapy which is allowed. Neoadjuvant/adjuvant therapy should have been completed at least 6 months prior to diagnosis of advanced and/or unresectable disease, and participants should not have received gemcitabine and/or cisplatin in the neoadjuvant/adjuvant setting. Participants who received prior neoadjuvant/adjuvant therapy with R2 postoperative pathology of the oncologic resection are excluded. 2. Has ampullary cancer. 3. Has small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology and/or mucinous cystic neoplasms. 4. Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. 5. Has undergone major surgery and has not recovered adequately from the procedure and/or complications from the surgery prior to starting study intervention. 6. A WOCBP who has a positive urine pregnancy test within 24 hours prior to administration of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 7. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PDL2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX- 40, CD137). 8. Has received prior anticancer therapy (eg, TACE, palliative surgery) for advanced unresectable biliary tract cancer (intra-or extra hepatic cholangiocarcinoma or gallbladder cancer), including investigational agents within 4 weeks prior to randomization. 9. Has not recovered (ie, AE =Grade 1 or baseline) from AEs due to previously administered anticancer therapy. Participants with =Grade 2 neuropathy may be eligible based on investigator assessment. 10. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and have not had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to noncentral nervous system (CNS) disease if deemed safe by the investigator. A 2-week washout period is required for a longer course of radiation (>2 weeks). 11. Has received a live vaccine within 30 days prior to the first dose of study intervention. 12. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. 13. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention. 14. Has a known additional invasive malignancy that is progressing or has required active treatment within the past 3 years. 15. Has severe hypersensitivity (=Grade 3) to pembrolizumab, gemcitabine, or cisplatin and/or any of their excipients. 16. Has a history of (noninfectious) pneumonitis that
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare overall survival (OS) between pembrolizumab plus gemcitabine/cisplatin and placebo plus gemcitabine/cisplatin;Secondary Objective: 1. To compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), as assessed by Blinded Independent Central Review (BICR), between pembrolizumab plus gemcitabine/cisplatin and placebo plus gemcitabine/cisplatin 2. To compare 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), between pembrolizumab plus gemcitabine/cisplatin and placebo plus gemcitabine/cisplatin 3. To evaluate duration of response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) 4. To evaluate the safety and tolerability profile of pembrolizumab plus gemcitabine/cisplatin ;Primary end point(s): 1. Overall Survival (OS);Timepoint(s) of evaluation of this end point: 1. Up to approximately 41 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR) 2. Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR 3. Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR 4. Number of Participants Who Experienced One or More Adverse Events (AEs) 5. Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE);Timepoint(s) of evaluation of this end point: 1. Up to approximately 41 months 2. Up to approximately 41 months 3. Up to approximately 41 months 4. Up to approximately 41 months 5. Up to approximately 41 months | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, France, Germany, Hong Kong, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, New Zealand, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactGCTO
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.
Outcome results
None listed