An open-label randomized trial of zanidatamab for advanced HER2positive biliary tract cancer

Phase 1

• Conditions: BTC - Biliary Tract Cancer; MedDRA version: 20.0Level: SOCClassification code: 10029104Term: Neoplasms benign malignant and unspecified (incl cysts and polyps) Class: 2; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-508219-21-00
• Lead Sponsor: Jazz Pharmaceuticals Ireland Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-04-18
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 243

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 randomization. 5. Assessable (measurable or non-measurable) disease as defined by RECIST 1.1, per investigator assessment. 6. Male or female = 18 years of age (or the legal age of adulthood per country-specific regulations)., 7. Eastern Cooperative Oncology Group (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) = 3 × upper limit of normal (ULN), and alanine aminotransferase (ALT) = 3 × ULN. For participants with liver involvement, AST and ALT = 5 × ULN is acceptable. b.Total bilirubin = 1.5 × ULN, or = 3 × ULN for participants with Gilbert’s disease 10. Adequate renal function, as defined by estimated glomerular filtration rate (GFR) > 50 mL/min per local institutional standard method. 11. Left ventricular ejection fraction (LVEF) = 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 randomization. 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-(HMA-CTCG, 2024)) 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 after the last dose of durvalumab. 14. Females must agree to not donate oocytes starting at screening and throughout the study period, and for at least 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 after the last dose of durvalumab. 15. Males must agree to use condoms an

Exclusion Criteria

1. Prior treatment with a HER2-targeted agent, with the exception of participants who completed HER2targeted treatment for breast cancer > 5 years prior to their diagnosis of BTC. 2. Prior treatment with checkpoint inhibitors, other than durvalumab or pembrolizumab as part of the up to 2 cycles of systemic therapy allowed prior to randomization per Inclusion Criterion 3. Exclusionary checkpoint inhibitors include but are not limited to other anti-PD-1, anti-PD-L1, anticytotoxic T lymphocyte-associated antigen (CTLA)-4 antibodies. 3. The following BTC histologic subtypes are excluded: small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology, and mucinous cystic neoplasms detected in the biliary tract region. 4. Received radiotherapy within 2 weeks of randomization. 5. Had major surgery within 4 weeks of randomization. 6. Total lifetime load of anthracycline exceeding 360 mg/m2 doxorubicin or equivalent. 7. Use of systemic corticosteroids administered at doses equivalent to > 10 mg per day of prednisone within 2 weeks of randomization. Topical, ocular, intra-articular, intranasal, and/or inhalation corticosteroids are permitted. 8. Brain metastases: Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks of randomization. Stable, treated brain metastases are allowed (defined as participants who are off steroids and anticonvulsants and are neurologically stable with no evidence of radiographic progression for at least 4 weeks at the time of screening). 9. Known history of or ongoing leptomeningeal disease (LMD). Participants will be eligible if LMD has been reported radiographically but is not suspected clinically by the investigator, and the participant does not have neurological symptoms of LMD. 10. Poorly controlled seizures in the judgment of the investigator., 11. Grade 2 or greater peripheral neuropathy. 12. Concurrent uncontrolled or active hepatobiliary disorders or untreated or ongoing complications after laparoscopic procedures or stent placement, including but not limited to active cholangitis, unresolved biliary obstruction, infected biloma, or abscess. Any complications must be resolved at least 2 weeks prior to randomization. 13. Prior or concurrent invasive malignancy whose natural history or treatment has, in the opinion of the investigator or medical monitor, the potential to interfere with the safety or efficacy assessment of the investigational regimen. 14. Severe chronic or active infections requiring systemic parenteral antibacterial, antifungal or antiviral therapy; or any other potentially life-threatening viral or bacterial infection (participants on oral antibiotics must complete the planned course of treatment prior to randomization). 15. Active hepatitis, including the following: a.Acute or chronic hepatitis B (Exception: Participants who are hepatitis B surface antigen [HBsAg] positive are eligible if they have hepatitis B virus (HBV) DNA less than 500 IU/mL or 2,500 copies/mL). Note: Participants with detectable HBsAg or detectable HBV DNA should be managed per institutional or local standards. Participants beginning antiviral agents at screening should be treated for > 2 weeks prior to randomization. b.Infection with hepatitis C (Exceptions: [i] Participants who have no history of curative viral treatment and are documented to be viral load negative are eligible; [ii] Participants who have

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified