Phase 3 Study of T-DXd and Rilvegostomig Versus SoC in Advanced HER2-expressing Biliary Tract Cancer
- Registration Number
- NCT06467357
- Lead Sponsor
- AstraZeneca
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 620
- 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
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Trastuzumab deruxtecan + rilvegostomig Agilent HercepTest™ mAb pharmDx Trastuzumab deruxtecan (T-DXd; DS-8201a) in combination with rilvegostomig arm Trastuzumab deruxtecan + rilvegostomig Rilvegostomig Trastuzumab deruxtecan (T-DXd; DS-8201a) in combination with rilvegostomig arm Trastuzumab deruxtecan + rilvegostomig Ventana PD-L1 SP263 assay Trastuzumab deruxtecan (T-DXd; DS-8201a) in combination with rilvegostomig arm Trastuzumab deruxtecan Agilent HercepTest™ mAb pharmDx Trastuzumab deruxtecan (T-DXd; DS-8201a) arm Trastuzumab deruxtecan Ventana PD-L1 SP263 assay Trastuzumab deruxtecan (T-DXd; DS-8201a) arm Standard of Care Agilent HercepTest™ mAb pharmDx Gemcitabine and cisplatin in combination with durvalumab arm Standard of Care Ventana PD-L1 SP263 assay Gemcitabine and cisplatin in combination with durvalumab arm Standard of Care Gemcitabine Gemcitabine and cisplatin in combination with durvalumab arm Trastuzumab deruxtecan + rilvegostomig Trastuzumab deruxtecan Trastuzumab deruxtecan (T-DXd; DS-8201a) in combination with rilvegostomig arm Trastuzumab deruxtecan Trastuzumab deruxtecan Trastuzumab deruxtecan (T-DXd; DS-8201a) arm Standard of Care Cisplatin Gemcitabine and cisplatin in combination with durvalumab arm Standard of Care Durvalumab Gemcitabine and cisplatin in combination with durvalumab arm
- Primary Outcome Measures
Name Time Method 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) Safety and tolerability will be evaluated with multiple endpoints including the proportion of treated patients with occurrence of AEs, SAEs, AESIs, and clinically significant change from baseline for Hematology, clinical chemistry, Urinalysis and vital signs.
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) Overall survival (OS) in 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.
- Secondary Outcome Measures
Name Time Method To assess time to deterioration in physical functioning in patients treated with T-DXd with rilvegostomig vs Standard of Care Until End of Study (estimated up to 48 months) Time to deterioration (TTD) in physical function as measured by the PROMIS Short Form v2.0 - Physical Function 8c - TTD is defined as time from the date of randomization to the date of deterioration.
Deterioration is defined as the change from baseline that reaches a clinically meaningful deterioration threshold.
...To assess time to deterioration in physical functioning in patients treated with T-DXd monotherapy vs Standard of care Until End of Study (estimated up to 48 months) Time to deterioration (TTD) in physical function as measured by the PROMIS Short Form v2.0 - Physical Function 8c - TTD is defined as time from the date of randomization to the date of deterioration.
Deterioration is defined as the change from baseline that reaches a clinically meaningful deterioration threshold.
...To assess time to deterioration in physical functioning in patients treated with T-DXd with rilvegostomig vs T-DXd monotherapy Until End of Study (estimated up to 48 months) Time to deterioration (TTD) in physical function as measured by the PROMIS Short Form v2.0 - Physical Function 8c - TTD is defined as time from the date of randomization to the date of deterioration.
Deterioration is defined as the change from baseline that reaches a clinically meaningful deterioration threshold.
...To assess the pharmacokinetics of T-DXd, total anti- HER2 antibody, DXd and rilvegostomig in serum From the time of informed consent until 30 and 90 days after the last dose of T-DXd and rilvegostomig, respectively Descriptive analysis of serum concentration of T-DXd, total anti-HER2 antibody, DXd and rilvegostomig in all applicable arms.
To investigate the immunogenicity of T-DXd and of rilvegostomig From the time of informed consent until 30 and 90 days after the last dose of T-DXd and rilvegostomig, respectively Descriptive summary of presence of ADAs for T-DXd and rilvegostomig in all applicable arms.
To describe patient-reported tolerability of T-DXd with rilvegostomig in comparison to Standard of Care based on overall side-effect bother Until End of Study (estimated up to 48 months) Patient-reported tolerability will be described using the Overall side-effect bother that will be mesured using PGI-TT
To describe patient-reported tolerability of T-DXd monotherapy in comparison to SoC based on overall side-effect bother Until End of Study (estimated up to 48 months) Patient-reported tolerability will be described using the Overall side-effect bother that will be assessed will be mesured using PGI-TT
To evaluate the efficacy of T-DXd with rilvegostomig vs Standard of Care in terms of Overall Survival in the ITT population (HER2 IHC 3+/2+) From date of randomization until the date of death from any cause (estimated to be assessed up to 48 months after first subject randomized) Overall Survival (OS) in ITT population (HER2 IHC 3+/2+) OS definition as above
To evaluate the efficacy of T-DXd monotherapy vs Standard of Care in terms of Overall Survival in the HER2 IHC 3+ population From date of randomization until the date of death from any cause (estimated to be assessed up to 48 months after first subject randomized) Overall Survival (OS) in HER2 IHC 3+ population OS definition as above
To evaluate the efficacy of T-DXd monotherapy vs Standard of Care in terms of Overall Survival in the ITT population From date of randomization until the date of death from any cause (estimated to be assessed up to 48 months after first subject randomized) Overall Survival (OS) in ITT population (HER2 IHC 3+/2+) OS definition as above
To further evaluate efficacy of T-DXd with rilvegostomig vs Standard of Care in terms of Progression Free Survival in HER2 IHC 3+ and ITT populations From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs first (estimated to be assessed up to 48 months) Progression free survival (PFS) in HER2 IHC 3+ and ITT populations. PFS is defined as time from randomization until progression per RECIST v1.1, or death due to any cause. The analysis will include all randomized patients, regardless of whether the patient withdraws from randomized therapy, receives another anticancer therapy or clinically progresses prior t...
To further evaluate efficacy of T-DXd monotherapy vs Standard of Care in terms of Progression Free Survival in HER2 IHC 3+ and ITT populations From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs first (estimated to be assessed up to 48 months) Progression free survival (PFS) in HER2 IHC 3+ and ITT populations. PFS is defined as time from randomization until progression per RECIST v1.1, or death due to any cause. The analysis will include all randomized patients, regardless of whether the patient withdraws from randomized therapy, receives another anticancer therapy or clinically progresses prior t...
To further evaluate the efficacy of T-DXd with rilvegostomig vs Standrad of Care in terms of objective response rate in the HER2 IHC 3+ and ITT populations Estimated up to 6 months since randomization Objective response rate (ORR) in HER2 IHC 3+ and ITT populations ORR is defined as the proportion of patients who achieved CR or PR per RECIST 1.1, confirmed by the investigator. The analysis will include objective response data for all randomized patients from randomization until progression, or up to the last evaluable assessment in the absence of progress...
To further evaluate the efficacy of T-DXd monotherapy vs Standrad of Care in terms of objective response rate in the HER2 IHC 3+ and ITT populations Estimated up to 6 months since randomization Objective response rate (ORR) in HER2 IHC 3+ and ITT populations ORR is defined as the proportion of patients who achieved CR or PR per RECIST 1.1, confirmed by the investigator. The analysis will include objective response data for all randomized patients from randomization until progression, or up to the last evaluable assessment in the absence of progress...
To further evaluate efficacy of T-DXd with rilvegostomig vs Standard if Care in terms of duration of response in patients with HER2-expressing BTC in the IHC 3+ and ITT populations From the date of first documented response until date of documented progression or death due to any cause, whichever occurs first (estimated up to 48 months) Duration of response (DoR) in HER2 IHC 3+ and ITT populations DoR will be defined as the time from the date of first documented response until date of documented progression per RECIST v1.1, or death due to any cause. The analysis will include all randomized patients who have a response, regardless of whether the patient withdraws from randomized therapy, re...
To further evaluate efficacy of T-DXd monotherapy vs Standard if Care in terms of duration of response in patients with HER2-expressing BTC in the IHC 3+ and ITT populations From the date of first documented response until date of documented progression or death due to any cause, whichever occurs first (estimated up to 48 months) Duration of response (DoR) in HER2 IHC 3+ and ITT populations DoR will be defined as the time from the date of first documented response until date of documented progression per RECIST v1.1, or death due to any cause. The analysis will include all randomized patients who have a response, regardless of whether the patient withdraws from randomized therapy, re...
To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of Overall survival in HER2 IHC 3+ and ITT populations. From the date of randomisation until progression or death due to any cause, whichever occurs first (estimated up to 48 months) Overall survival (OS) in 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.
To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of PFS in HER2 IHC 3+ and ITT populations. From the date of randomisation until progression or death due to any cause, whichever occurs first (estimated up to 48 months) Progression free survival (PFS) in HER2 IHC 3+ and ITT populations. PFS is defined as time from randomization until progression per RECIST v1.1, or death due to any cause. The analysis will include all randomized patients, regardless of whether the patient withdraws from randomized therapy, receives another anticancer therapy or clinically progresses prior t...
To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of Duration of response in HER2 IHC 3+ and ITT populations. From the date of first response until progression or death due to any cause, whichever occurs first (estimated up to 48 months) Duration of response (DoR) in HER2 IHC 3+ and ITT populations DoR will be defined as the time from the date of first documented response until date of documented progression per RECIST v1.1, or death due to any cause. The analysis will include all randomized patients who have a response, regardless of whether the patient withdraws from randomized therapy, re...
To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of Objective response rate in HER2 IHC 3+ and ITT populations. Estimated up to 6 months Objective response rate (ORR) in HER2 IHC 3+ and ITT populations ORR is defined as the proportion of patients who achieved CR or PR per RECIST 1.1, confirmed by the investigator. The analysis will include objective response data for all randomized patients from randomization until progression, or up to the last evaluable assessment in the absence of progress...
To assess the safety and tolerability of T-DXd with rilvegostomig vs Standard of Care From first dose of study intervention until 90 days after the last dose except for ILD/pneumonitis, where safety follow-up will be continued until resolution. Safety and tolerability will be evaluated with multiple endpoints including the proportion of treated patients with occurrence of AEs, SAEs, AESIs, and clinically significant change from baseline for Hematology, clinical chemistry, Urinalysis and vital signs.
To assess the safety and tolerability of T-DXd monotherapy vs Standard of Care From first dose of study intervention until 90 days after the last dose except for ILD/pneumonitis, where safety follow-up will be continued until resolution. Safety and tolerability will be evaluated with multiple endpoints including the proportion of treated patients with occurrence of AEs, SAEs, AESIs, and clinically significant change from baseline for Hematology, clinical chemistry, Urinalysis and vital signs.
To describe patient-reported tolerability of T-DXd with rilvegostomig in comparison to Standard of Care based on a summary of symptomatic AEs Until End of Study (estimated up to 48 months) Patient-reported tolerability will be described using the Symptomatic adverse events: Descriptive summary of the proportion of patients reporting symptomatic AEs while on treatment using items from the EORTC Item Library (on EORTC IL form 322).
To describe patient-reported tolerability of T-DXd monotherapy in comparison to SoC based on a summary of symptomatic AEs Until End of Study (estimated up to 48 months) Patient-reported tolerability will be described using the Symptomatic adverse events: Descriptive summary of the proportion of patients reporting symptomatic AEs while on treatment using items from the EORTC Item Library (on EORTC IL form 322)
To describe patient-reported tolerability of T-DXd with rilvegostomig in comparison to T-DXd monotherapy based on a summary of symptomatic AEs and overall side-effect bother Until End of Study (estimated up to 48 months) Symptomatic AEs and overall side-effect bother definitions as above
Trial Locations
- Locations (1)
Research Site
🇻🇳Vinh, Vietnam