locally advanced unresectable or metastatic BTC
Conditions
Interventions
Experimental group:Zanidatamab with standard-of-care therapy
Control group:Standard-of-care therapy
Sponsors
Jilin Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Histologically- or cytologically-confirmed BTC, including GBC, ICC, or ECC. 2. Locally advanced unresectable or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies. 3. Received no more than 2 cycles of systemic therapy which is limited to gemcitabine and cisplatin with or without a PD-1/L1 inhibitor (physician’s choice of durvalumab or pembrolizumab, where approved under local regulations) for advanced unresectable or metastatic disease. Participants who have received prior adjuvant or neoadjuvant treatment (including investigational products) for earlier stage disease are permitted as long as therapy was completed more than 6 months prior to expected date of C1D1. 4. HER2-positive disease (defined as IHC 3+; or IHC 2+/ ISH+) by IHC and ISH assay (in participants with IHC 2+ tumors) at a central laboratory on new biopsy tissue or archival tissue from the most recent biopsy. Note that fine needle aspirates (FNAs; cytology samples) and biopsies from sites of bone metastases are not acceptable. Testing may occur with tissue obtained at any time after diagnosis of BTC and before expected date of randomization. a. When the central laboratory is available, samples must be sent to the central laboratory prior to randomization for determination of HER2 status. If it has been confirmed with the medical monitor that a central laboratory is not available, sites may use local testing for HER2 to enroll participants with IHC 3+ tumors. In this case, samples still must be sent to the central laboratory for confirmatory analyses once the central laboratory becomes available. 5. Assessable (measurable or non-measurable) disease as defined by RECIST 1.1, per investigator assessment. 6. Male or female >= 18 years or age (or the legal age of adulthood per country-specific regulations). 7. ECOG performance status of 0 or 1. 8. Adequate hematologic function as follows: a. Absolute neutrophil count (ANC) >= 1.5 × 109/L b. Platelet count = 100 × 109/L, not requiring transfusion support c. Hemoglobin (Hgb) >= 9 g/dL (participants with chronic anemia that is supported by intermittent red blood cell transfusions are eligible); 9. Adequate hepatic function, as defined by both: a. Aspartate aminotransferase (AST) 50 mL/min per local institutional standard method. 11. Left ventricular ejection fraction >= 50% as determined by either echocardiogram or multiple gated acquisition scan (MUGA). 12. Females of childbearing potential must have a negative serum/plasma or urine beta human chorionic gonadotropin (ß-hCG) pregnancy test result within 3 days prior to expected date of C1D1. Females with false positive results can be enrolled if subsequent serum/plasma testing is negative. 13. Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control with a failure rate of less than 1% per year (HMA-CTFG, 2020) during the study and for 14 months after the last dose of cisplatin, 6 months after the last dose of gemcitabine, 5 months after the last dose of zanidatamab, 4 months after the last dose of pembrolizumab, and 3 months a
Exclusion criteria
Exclusion criteria: 1. Subjects who have previously received HER2-targeted drug therapy for breast cancer, except those who completed HER2-targeted therapy for breast cancer > 5 years before diagnosis of BTC. 2. Prior checkpoint inhibitor therapy, except for use of duvaliuzumab or pembrolizumab as part of systemic therapy up to 2 cycles prior to the projected C1D1 date permitted under inclusion criteria 3. Exclusion checkpoint inhibitors include, but are not limited to, other anti-PD-1, anti-PD-L1, anti-cytotoxic T lymphocyte-associated antigen (CTLA-4) antibodies. 3. The following subtypes of BTC were excluded: small cell carcinoma, neuroendocrine tumor, lymphoma, sarcoma, mixed tumor histology, and mucinous cystic tumor found in the biliary tract. 4. Received radiotherapy within 2 weeks prior to the estimated C1D1 date. 5. Major surgery within 4 weeks before the estimated C1D1 date. 6. A lifetime total load of anthracyclines exceeding 360 mg/ m2 doxorubicin or its equivalent. 7. A systemic corticosteroid equivalent to a dose of > 10 mg/ day of prednisone has been used in the 2 weeks prior to the estimated C1D1 date. Topical, ocular, intra-articular, intranasal, and/or inhaled corticosteroids are permitted. 8. Brain metastases: The presence of untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation therapy for CNS metastases within 4 weeks prior to the expected C1D1 date. The presence of treated stable brain metastases (defined as the subject being off steroids and anticonvulsants and having a stable nervous system with no evidence of radiological progression for at least 4 weeks at the time of screening) was allowed. 9. Known history of pia meningeal disease (LMD) or persistent LMD. If imaging studies report LMD, but the investigator does not suspect LMD clinically, and the subject has no neurological symptoms of LMD, the subject will be eligible for study enrollment. 10. In the investigator's judgment, there were poorly controlled seizures. 11. Peripheral neuropathy of grade 2 or above is present. 12. Complications of uncontrolled or active hepatobiliary disease, or untreated or ongoing complications following laparoscopic surgery or stenting, including but not limited to active cholangitis, unresolved biliary obstruction, infectious biliomas, or abscesses. Any complications must resolve at least 2 weeks before the expected C1D1 date. 13. Have prior or concurrent aggressive malignancies whose natural course of disease or treatment, in the opinion of the investigator or medical monitor, may interfere with the evaluation of the safety or efficacy of the study protocol. 14. Severe chronic or active infections requiring systemic parenteral antimicrobial, antifungal, or antiviral treatment; Or any other potentially life-threatening viral or bacterial infection (subjects receiving oral antibiotics must complete the planned course of treatment by the estimated C1D1 date). 15. Active hepatitis includes the following diseases: a. Acute or chronic hepatitis B (exception: Subjects who are positive for hepatitis B surface antigen [HbsAg] and have less than 500 IU/mL or 2,500 copies /mL of hepatitis B virus [HBV]DNA are eligible for study enrollment). Note: Subjects with detectable HbsAg or HBVDNA should be managed according to institutional or local standards. Subjects starting antiviral drugs at the time of screening should be treated > 2 weeks prior to the expected C1D1 date. b. Hepatitis C infection (exceptions: [i] Subjects w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate;Maximum Tolerated Dose;Progression-free survival (PFS) as assessed by immunohistochemistry (IHC) 3+ subgroup against Solid Tumor Efficacy Evaluation Criteria 1.1 (RECIST 1.1); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival (OS) of the IHC 3+ subgroup;Overall population PFS assessed according to RECIST 1.1;Overall population of OS;Confirmed objective response rate (cORR) as assessed by RECIST 1.1;Duration of response (DOR) assessed according to RECIST 1.1;The frequency, severity, severity, and correlation of adverse events (aes) occurring during treatment;Changes of serum concentration of Zanidatamab with time after administration;Frequency, duration, and time of onset of anti-Zanidatamab antibodies and Zanidatamab neutralizing antibodies (if applicable);Patient-reported field scores for PF measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Item (QLQ-C30) in the IHC 3+ subgroup Defined Time to deterioration from baseline (TDD);Overall population patients using EORTC QLQ-C30 measurements reported PF domain scores compared to baseline TDD;Patients in the IHC 3+ subgroup using the EORTC Quality of Life Questionaire - Cholangiocarcinoma and Gallbladder Cancer Module (QLQ-BIL21) (pain, jaundice, abdominal pain, and pruritus) reported symptoms compared to baseline TDD;Overall population patients with EORTC QLQ-BIL21 (pain, jaundice, abdominal pain, and pruritus) reported symptom scores compared to baseline TDD; | — |
Countries
China
Contacts
Public ContactCheng Ying
Jilin Cancer Hospital
Outcome results
None listed