Biliary Tract Cancer
Conditions
Keywords
Rilvegostomig, Durvalumab, Biliary Tract Cancer, Bispecific Antibody, PD-L1, TIGIT, Initially Unresectable, Recurrent, Intra-hepatic cholangiocarcinoma, Extra-hepatic cholangiocarcinoma, Gallbladder cancer
Brief summary
The purpose of this study is to measure the efficacy and safety of rilvegostomig with gemcitabine plus cisplatin vs. durvalumab with gemcitabine plus cisplatin as first line treatment for patients with advanced BTC.
Interventions
DRUGRilvegostomig
Rilvegostomig IV (intravenous) Q3W
DRUGDurvalumab
Durvalumab 1500mg IV (intravenous) Q3W for up to 8 cycles (21days). Then Q4W.
Gemcitabine/Cisplatin IV (Intravenous) 1000 mg/m2 plus cisplatin 25 mg/m2 on Day 1 and Day 8 of each 21-day cycle
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key inclusion Criteria: * Histologically confirmed adenocarcinoma of the biliary tract, including intra-hepatic or extra-hepatic cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC). * Unresectable locally advanced or metastatic BTC, previously untreated in the advanced disease setting * Known PD-L1 status assessed at a central laboratory using an acceptable tumor sample. * Measurable disease by RECIST 1.1 criteria using CT or MRI and is suitable for accurate repeated measurements. * ECOG Performance Status of 0 or 1 with no deterioration (ie, ECOG PS \> 1) over the previous 2 weeks prior to baseline at screening and prior to randomization. * Adequate bone marrow and organ function. Key
Exclusion criteria
* Ampullary carcinoma * Any prior systemic therapy received for unresectable, locally advanced or metastatic BTC. * Any prior exposure to any other therapy targeting immune-regulatory receptors or mechanisms. * Any concurrent chemotherapy, radiotherapy, immunotherapy, investigational, biologic, or hormonal therapy for cancer treatment other than those under investigation in this study. * Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment. * Active or ongoing interstitial lung disease/pneumonitis (of any grade), serious chronic gastrointestinal conditions associated with diarrhea, or active non-infectious skin disease (including any grade rash, urticaria, dermatitis, ulceration, or psoriasis) requiring systemic treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in the PDL1 ≥ 1% population | approximately 4 years | Overall Survival is defined as time from randomization until the date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival in the intent to treat (ITT) population | approximately 4 years | Overall Survival is defined as time from randomization until the date of death due to any cause. |
| Progression Free Survival (PFS) in the PDL1 ≥ 1% population | approximately 4 years | PFS is defined as the time from randomization until radiological progression per RECIST 1.1, or death due to any cause (in the absence of progression), whichever occurs first. |
| Progression Free Survival (PFS) in the intent to treat (ITT) population | approximately 4 years | PFS is defined as the time from randomization until radiological progression per RECIST 1.1 or death due to any cause (in the absence of progression), whichever occurs first. |
| Objective Response Rate (ORR) in the PDL1 ≥ 1% population | approximately 4 years | ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR using RECIST 1.1. |
| Objective Response Rate (ORR) in the intent to treat (ITT) population | approximately 4 years | ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR using RECIST 1.1. |
| Duration of Response (DoR) in the PDL1 ≥ 1% population | approximately 4 years | DoR is defined as the time from the date of first documented response until the date of documented progression using RECIST 1.1 or death due to any cause (in the absence of progression), whichever occurs first. |
| Duration of Response (DoR) in the intent to treat (ITT) population | approximately 4 years | DoR is defined as the time from the date of first documented response until the date of documented progression using RECIST 1.1 or death due to any cause (in the absence of progression), whichever occurs first. |
| Time to Second Progression or death (PFS2) in the PDL1 ≥ 1% population | approximately 4 years | PFS2 is defined as the time from randomization until the earliest of the progression event (following the initial progression event), after the start of the first subsequent therapy, or death from any cause, whichever occurs first. |
| Time to Second Progression or death (PFS2) in the intent to treat (ITT) population | approximately 4 years | PFS2 is defined as the time from randomization until the earliest of the progression event (following the initial progression event), after the start of the first subsequent therapy, or death from any cause, whichever occurs first. |
| Assess the safety and tolerability of rilvegostomig in combination with chemotherapy vs durvalumab in combination with chemotherapy | approximately 4 years | Safety and tolerability will be evaluated by the proportion of treated patients with occurrence of AEs and SAEs as assessed by CTCAE v5.0. |
| Immunogenicity of Rilvegostomig | approximately 4 years | Presence of ADA for rilvegostomig (confirmatory results, titres and neutralising antibodies for confirmed positive samples). |
| PK of rilvegostomig: Lowest observed concentration of study drug before the next dose is administered (Ctrough) | Up to 12 weeks after disease progression | Lowest observed plasma concentration of the study drug (Ctrough) prior to next dose |
| PK of rilvegostomig: Maximum plasma concentration of the study drug (Cmax) | Up to 12 weeks after disease progression | Maximum observed plasma concentration of rilvegostomig |
| Serum rilvegostomig concentration | Up to 12 weeks after disease progression | To assess drug exposure (serum concentration) of IV rilvegostomig. |
| Assess patient reported biliary tract cancer symptoms (pain) | Up to 12 weeks post disease progression | Patient reported biliary tract cancer symptoms (pain) will be evaluated by the proportion of randomized patients with maintained or improved pain as assessed by the EORTC Item Library 445 and EORTC Item Library 446 (custom questionnaires that include measures of pain-in back, in stomach area, during the night; min/max values from 1-4, with higher scores indicating a worse outcome). |
| Assess patient reported global health status/quality of life (GHS/QoL) | Up to 12 weeks post disease progression | Patient reported GHS/QoL will be evaluated by the proportion of randomized patients with maintained or improved GHS/QoL as assessed by the EORTC Item Library 172 (custom questionnaire that includes measures of overall health and overall quality of life; min/max values from 1-7, with higher scores indicating a better outcome). |
Countries
Australia, Belgium, Brazil, Canada, China, France, Germany, India, Italy, Japan, Netherlands, Poland, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed