phase 3 study of t-dxd and rilvegostomig versus soc in advanced her2-expressing biliary tract cancer

Conditions: Biliary Tract Cancer

Summary: the purpose of this study is to measure the efficacy and safety of t-dxd with rilvegostomig or t-dxd monotherapy compared with gemcitabine plus cisplatin and durvalumab in patients with advanced treatment naïve her2-expressing btc.


Eligibility criteria:
key inclusion criteria: * participants must be ≥ 18 years of age at the time of screening. other age restrictions may apply as per local regulations; * male and female; * unresectable, previously untreated, locally advanced or metastatic btc. prior treatment in the perioperative and/or adjuvant setting is permissible provided there is \> 6 months (180 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; * provision of ffpe tumor sample that is no older than 3 years; * 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; * 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; key exclusion criteria: * prior exposure to other her2 targeting therapies, adcs, immune checkpoint inhibitors and therapeutic anticancer vaccines; * histologically confirmed ampullary carcinoma; * history of substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions; * 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 (\< 6 months) cardiovascular event including stroke; * serious chronic gastrointestinal conditions associated with diarrhea (eg, active inflammatory bowel disease); active non-infectious skin disease (including any grade rash, urticaria, dermatitis, ulceration, or psoriasis) requiring systemic treatment; * active autoimmune, connective tissue or inflammatory disorders that has required systemic treatment in the past 2 years, or where there is documented, or a suspicion of pulmonary involvement at the time of screening; * corrected qt interval (qtcf) prolongation to \> 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; * prior pneumonectomy (complete); * uncontrolled infection requiring iv antibiotics, antivirals, or antifungals; * active primary immunodeficiency, known uncontrolled active hiv infection or hcv; * pregnant or breastfeeding female patients, or patients who are planning to become pregnant; * participation in another clinical study with a study intervention or investigational medicinal device administered in the last 6 months prior to randomization, or concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study (only randomized portion).

Keywords: biliary tract cancer her2 her2 expressing btc trastuzumab deruxtecan t-dxd rilvegostomig