Biliary Tract Cancer
Conditions
Interventions
Drug: Gemcitabine
Drug: Cisplatin
Drug: Durvalumab
Drug: Trastuzumab deruxtecan
Drug: Rilvegostomig
Diagnostic Test: Agilent HercepTest mAb pharmDx
Diagnostic Test: Ventana PD-L1 SP263 assay
Sponsors
Hibi Kazushige
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male and female patients must be at least 18 years of age at the time of signing the informed consent. Other age restrictions may apply as per local regulations. - Unresectable, previously untreated, locally advanced or metastatic biliary tract adenocarcinoma. Prior treatment in the perioperative and/or adjuvant setting is permissible provided there is > 3 months (90 days) between the end of adjuvant treatment and the diagnosis of locally advanced or metastatic disease. - Histologically confirmed HER2-expressing (IHC 3+ or IHC 2+) BTC. - Patients must provide an FFPE tumor sample that is no older than 3 years for tissue-based IHC staining to centrally determine HER2 expression, PD-L1 status, and other correlatives. - Has at least one target lesion assessed by the Investigator based on RECIST v1.1. (Randomized portion only) - WHO/ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing. - Adequate organ and bone marrow function within 14 days before randomization. - Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential. - Minimum life expectancy of 12 weeks.
Exclusion criteria
Exclusion criteria: - Prior exposure to other HER2 targeting therapies, ADCs, immune checkpoint inhibitors and therapeutic anticancer vaccines. - Histologically confirmed ampullary carcinoma. - Any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the Investigator, interfere with the patient's participation in the clinical study or evaluation of the clinical study results. - Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. - Medical history of myocardial infarction within 6 months before randomization/enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV), unstable angina pectoris, clinically important cardiac arrhythmias, or a recent ( 470 msec (females) or > 450 msec (males) based on average of the screening triplicate 12-lead ECG. - History of (non-infectious) ILD/pneumonitis, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. - Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion etc). - Prior pneumonectomy (complete). - Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. Patients with prior cholangitis/biliary tract infections/biliary intervention (eg, stent, external drain) should have completed a full course of antibiotics prior to randomization. - Active primary immunodeficiency, known uncontrolled active HIV infection or HCV. - History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected nonmelanoma skin cancer and curatively treated in situ disease. For certain participant populations, exceptions could also include carcinomas in-situ or Ta tumors treated with curative intent. - Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (Drainage and Cell free and Concentrated Ascites Reinfusion Therapy are not allowed within 2 weeks prior to screening assessment). - Any concurrent anticancer treatment without an adequate washout period prior to randomization. Concurrent use of hormonal therapy for non-cancer related conditions (eg, hormone replacement therapy) is allowed. - History of organ transplants or allogenic stem cell transplant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.Safety Run In: To evaluate the safety and tolerability of T-DXd with rilvegostomig Safety and tolerability will be evaluated by the proportion of treated patients with occurrence of AEs, SAEs and AESIs, as assessed by CTCAE v5.0. 2.Randomized Portion: To evaluate the efficacy of T-DXd with rilvegostomig vs Standard of Care (SoC) in terms of Overall Survival in the FAS (HER2 IHC 3+) population Overall survival (OS) in FAS (HER2 IHC 3+) population OS is defined as time from randomization date until the date of death due to any cause. The comparison will include all randomized patients, regardless of whether the patient withdraws from therapy or receives another anticancer therapy. The measure of interest is the hazard ratio of OS. | — |
Countries
Austria, Belgium, Brazil, Canada, Germany, Japan, Netherlands, South Korea, Taiwan
Contacts
Public ContactKazushige Hibi
Astrazeneka K.K
Outcome results
None listed