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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
Phase 3 trial testing Pembrolizumab in Biliary Tract Carcinoma in 158 participants. Completed in 25 March 2025.
| Lead sponsor | Merck Sharp & Dohme LLC |
|---|---|
| Phase | Phase 3 |
| Status | Completed |
| Study type | INTERVENTIONAL |
| Allocation | randomized |
| Design | parallel |
| Masking | triple |
| Primary purpose | treatment |
| Enrollment | 158 |
| Start date | 10 July 2020 |
| Primary completion | 15 December 2022 |
| Estimated completion | 25 March 2025 |
| Sites | 22 locations across China |
Merck Sharp & Dohme LLC — full company profile →
18 and older, any sex, with Biliary Tract Carcinoma. Patients with the condition only — healthy volunteers not accepted.
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Overall survival was defined as the time from randomization to death due to any cause. Per protocol the final reported outcome for OS did not include any sensitivity or supportive analysis.
| Group | Value | 95% CI |
|---|---|---|
| Arm A: Pembrolizumab + Chemotherapy | 14.1 | 10.4 – 17.7 |
| Arm B: Placebo + Chemotherapy | 9.9 | 8.6 – 13.0 |
PFS was defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS as assessed by BICR per RECIST 1.1 was presented.
| Group | Value | 95% CI |
|---|---|---|
| Arm A: Pembrolizumab + Chemotherapy | 5.6 | 3.2 – 7.4 |
| Arm B: Placebo + Chemotherapy | 5.7 | 4.4 – 6.9 |
ORR was defined as the percentage of participants who had 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 was adjusted for this study to allow a maximum of 10 target lesions in total and 5 per organ.
| Group | Value | 95% CI |
|---|---|---|
| Arm A: Pembrolizumab + Chemotherapy | 36.0 | 25.2 – 47.9 |
| Arm B: Placebo + Chemotherapy | 28.9 | 19.5 – 39.9 |
For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance o
| Group | Value | 95% CI |
|---|---|---|
| Arm A: Pembrolizumab + Chemotherapy | 10.2 | 5.4 – NA |
| Arm B: Placebo + Chemotherapy | 5.7 | 4.2 – 14.0 |
An adverse event (AE) was 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 was considered related to the medical treatment or procedure, that occurred during the course of the study. Number of participants who experienced one or more AEs was reported.
| Group | Value | 95% CI |
|---|---|---|
| Arm A: Pembrolizumab + Chemotherapy | 73 | |
| Arm B: Placebo + Chemotherapy | 82 |
An AE was 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 was considered related to the medical treatment or procedure, that occurred during the course of the study. Number of participants who discontinued study intervention (includes any study medication given during the study) due to an AE were reported.
| Group | Value | 95% CI |
|---|---|---|
| Arm A: Pembrolizumab + Chemotherapy | 18 | |
| Arm B: Placebo + Chemotherapy | 14 |
Time frame: Up to approximately 56 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.
| Reaction | System | First Course: Arm A: Pembr… | First Course: Arm B: Place… | Second Course: Arm A: Pemb… |
|---|---|---|---|---|
| Platelet count decreased | Investigations | — | — | — |
| Anaemia | Blood and lymphatic system disorders | — | — | — |
| Jaundice cholestatic | Hepatobiliary disorders | — | — | — |
| Neutrophil count decreased | Investigations | — | — | — |
| Biliary tract infection | Infections and infestations | — | — | — |
| White blood cell count decreased | Investigations | — | — | — |
| Myelosuppression | Blood and lymphatic system disorders | — | — | — |
| Myocarditis | Cardiac disorders | — | — | — |
| Death | General disorders | — | — | — |
| Biliary obstruction | Hepatobiliary disorders | — | — | — |
| Febrile infection | Infections and infestations | — | — | — |
| Alanine aminotransferase increased | Investigations | — | — | — |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | — | — | — |
| Hypertension | Vascular disorders | — | — | — |
| Leukocytosis | Blood and lymphatic system disorders | — | — | — |
| Myocardial infarction | Cardiac disorders | — | — | — |
| Hypopituitarism | Endocrine disorders | — | — | — |
| Abdominal discomfort | Gastrointestinal disorders | — | — | — |
| Ascites | Gastrointestinal disorders | — | — | — |
| Ileus | Gastrointestinal disorders | — | — | — |
| Intestinal ischaemia | Gastrointestinal disorders | — | — | — |
| Intestinal obstruction | Gastrointestinal disorders | — | — | — |
| Vomiting | Gastrointestinal disorders | — | — | — |
| Multiple organ dysfunction syndrome | General disorders | — | — | — |
| Pyrexia | General disorders | — | — | — |
| Reaction | System | First Course: Arm A: Pembr… | First Course: Arm B: Place… | Second Course: Arm A: Pemb… |
|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | — | — | — |
| White blood cell count decreased | Investigations | — | — | — |
| Neutrophil count decreased | Investigations | — | — | — |
| Platelet count decreased | Investigations | — | — | — |
| Nausea | Gastrointestinal disorders | — | — | — |
| Vomiting | Gastrointestinal disorders | — | — | — |
| Aspartate aminotransferase increased | Investigations | — | — | — |
| Alanine aminotransferase increased | Investigations | — | — | — |
| Decreased appetite | Metabolism and nutrition disorders | — | — | — |
| Constipation | Gastrointestinal disorders | — | — | — |
| Hypoalbuminaemia | Metabolism and nutrition disorders | — | — | — |
| Blood bilirubin increased | Investigations | — | — | — |
| Hyponatraemia | Metabolism and nutrition disorders | — | — | — |
| Rash | Skin and subcutaneous tissue disorders | — | — | — |
| Asthenia | General disorders | — | — | — |
| Weight decreased | Investigations | — | — | — |
| Lymphocyte count decreased | Investigations | — | — | — |
| Hypokalaemia | Metabolism and nutrition disorders | — | — | — |
| Hypothyroidism | Endocrine disorders | — | — | — |
| Diarrhoea | Gastrointestinal disorders | — | — | — |
| Malaise | General disorders | — | — | — |
| Blood alkaline phosphatase increased | Investigations | — | — | — |
| Gamma-glutamyltransferase increased | Investigations | — | — | — |
| Hypomagnesaemia | Metabolism and nutrition disorders | — | — | — |
| Alopecia | Skin and subcutaneous tissue disorders | — | — | — |
| Abdominal pain upper | Gastrointestinal disorders | — | — | — |
| Pyrexia | General disorders | — | — | — |
| Hyperuricaemia | Metabolism and nutrition disorders | — | — | — |
| Hypochloraemia | Metabolism and nutrition disorders | — | — | — |
| Blood creatinine increased | Investigations | — | — | — |
| Abdominal distension | Gastrointestinal disorders | — | — | — |
| Hyperglycaemia | Metabolism and nutrition disorders | — | — | — |
| Dizziness | Nervous system disorders | — | — | — |
| Ascites | Gastrointestinal disorders | — | — | — |
| Fatigue | General disorders | — | — | — |
| Upper respiratory tract infection | Infections and infestations | — | — | — |
| Abdominal pain | Gastrointestinal disorders | — | — | — |
| Hepatic function abnormal | Hepatobiliary disorders | — | — | — |
| Bile acids increased | Investigations | — | — | — |
| Blood lactate dehydrogenase increased | Investigations | — | — | — |
Most-reported serious reactions: Platelet count decreased, Anaemia, Jaundice cholestatic, Neutrophil count decreased, Biliary tract infection, White blood cell count decreased, Myelosuppression, Myocarditis.
Data from ClinicalTrials.gov NCT04924062 adverse events section.
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).
8 peer-reviewed publications reference this trial (live from Europe PMC):
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