Clinical trial
DESTINY-Biliary Tract Cancer-01: A Phase 3 Study of Trastuzumab Deruxtecan (T-DXd) and Rilvegostomig Versus Standard-of-Care Gemcitabine, Cisplatin, and Durvalumab for First Line Locally Advanced or Metastatic HER2-expressing Biliary Tract Cancer
Name
D781PC00001
Description
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.
Trial arms
Trial start
2024-06-26
Estimated PCD
2028-04-26
Trial end
2029-03-30
Status
Not yet recruiting
Phase
Early phase I
Treatment
Gemcitabine
Standard of care chemotherapy by intravenous infusion
Arms:
Standard of Care
Cisplatin
Standard of care chemotherapy by intravenous infusion
Arms:
Standard of Care
Durvalumab
Standard of care immunotherapy by intravenous infusion
Arms:
Standard of Care
Trastuzumab deruxtecan
Experimental therapy by intravenous infusion
Arms:
Trastuzumab deruxtecan, Trastuzumab deruxtecan + rilvegostomig
Other names:
DS-8201a; T-DXd
Rilvegostomig
Experimental therapy by intravenous infusion
Arms:
Trastuzumab deruxtecan + rilvegostomig
Agilent HercepTest™ mAb pharmDx
A semi-quantitative immunohistochemical assay to determine HER2 overexpression in FFPE breast cancer tissues routinely processed for histological evaluation.
Based on a primary monoclonal rabbit antibody which visualises Her2 overexpression utilising a fully automated IHC platform (Dako Omnis).
Arms:
Standard of Care, Trastuzumab deruxtecan, Trastuzumab deruxtecan + rilvegostomig
Ventana PD-L1 SP263 assay
A qualitative immunohistochemical assay to determine the level of PD-L1 expression in FFPE non-small cell lung cancer (NSCLC) tissues routinely processed for histological evaluation. Based on a rabbit monoclonal anti-PD-L1 clone SP263 which visualises PD-L1 protein using a VENTANA BenchMark ULTRA instrument
Arms:
Standard of Care, Trastuzumab deruxtecan, Trastuzumab deruxtecan + rilvegostomig
Size
620
Primary endpoint
Safety Run In: To evaluate the safety and tolerability of T-DXd with rilvegostomig
Until all patients have completed at least 1 full Cycle (each cycle is 21 days)
Randomized Portion: To evaluate the efficacy of T-DXd with rilvegostomig vs Standard of Care (SoC) in terms of Overall Survival in the HER2 IHC 3+ population
From date of treatment assignment until the date of death from any cause (estimated to be assessed up to 48 months after first subject randomized)
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).
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'This is an open-label, Sponsor-blinded study. To maintain the integrity of the study, Sponsor personnel directly involved in study conduct will not undertake or have access to efficacy data aggregated by treatment group prior to final data readout for the primary endpoint.'}}, 'enrollmentInfo': {'count': 620, 'type': 'ESTIMATED'}}
Updated at
2024-06-21
1 organization
1 product
4 drugs
1 indication
Organization
AstraZenecaDrug
GemcitabineIndication
Bile Duct CancerDrug
CisplatinDrug
AN0025Drug
TrastuzumabProduct
Rilvegostomig