NCT06467357招募中3 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 620
- 试验地点
- 275
- 主要终点
- Safety Run In: To evaluate the safety and tolerability of T-DXd with rilvegostomig
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •(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.
排除标准
- •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 (< 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 (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.
研究组 & 干预措施
Trastuzumab deruxtecan + rilvegostomig
Experimental
Trastuzumab deruxtecan (T-DXd; DS-8201a) in combination with rilvegostomig arm
干预措施: Rilvegostomig (Drug)
Standard of Care
Active Comparator
Gemcitabine and cisplatin in combination with durvalumab arm
干预措施: Gemcitabine (Drug)
Standard of Care
Active Comparator
Gemcitabine and cisplatin in combination with durvalumab arm
干预措施: Cisplatin (Drug)
Trastuzumab deruxtecan
Experimental
Trastuzumab deruxtecan (T-DXd; DS-8201a) arm
干预措施: Trastuzumab deruxtecan (Drug)
Trastuzumab deruxtecan + rilvegostomig
Experimental
Trastuzumab deruxtecan (T-DXd; DS-8201a) in combination with rilvegostomig arm
干预措施: Trastuzumab deruxtecan (Drug)
Standard of Care
Active Comparator
Gemcitabine and cisplatin in combination with durvalumab arm
干预措施: Durvalumab (Drug)
结局指标
主要结局
Safety Run In: To evaluate the safety and tolerability of T-DXd with rilvegostomig
时间窗: Until all patients have completed at least 1 full Cycle (each cycle is 21 days)
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.
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
时间窗: From date of treatment randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized)
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.
次要结局
- To evaluate the efficacy of T-DXd with rilvegostomig vs Standard of Care in terms of Overall Survival in the FAS (HER2 IHC 3+/2+) population(From date of randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized))
- To evaluate the efficacy of T-DXd monotherapy vs Standard of Care in terms of Overall Survival in the FAS (HER2 IHC 3+) population(From date of randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized))
- To evaluate the efficacy of T-DXd monotherapy vs Standard of Care in terms of Overall Survival in the FAS (HER2 IHC 3+/2+) population(From date of randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized))
- To further evaluate efficacy of T-DXd with rilvegostomig vs Standard of Care in terms of Progression Free Survival in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) 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 50 months))
- To further evaluate efficacy of T-DXd monotherapy vs Standard of Care in terms of Progression Free Survival in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) 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 50 months))
- To further evaluate the efficacy of T-DXd with rilvegostomig vs Standrad of Care in terms of objective response rate in the FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) 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 50 months))
- To further evaluate the efficacy of T-DXd monotherapy vs Standrad of Care in terms of objective response rate in the FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) 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 50 months))
- 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 FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) 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 50 months))
- 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 FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) 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 50 months))
- To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of Overall survival in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations.(From date of randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized))
- To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of PFS in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations(From the date of randomisation until progression or death due to any cause, whichever occurs first (estimated up to 50 months))
- To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of Duration of response in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations(From the date of first response until progression or death due to any cause, whichever occurs first (estimated up to 50 months))
- To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of Objective response rate in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) 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 50 months))
- To assess the safety and tolerability of T-DXd with rilvegostomig vs Standard of Care(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 50 months))
- To describe patient-reported tolerability of T-DXd with rilvegostomig in comparison to T-DXd monotherapy based on a summary of symptomatic AEs(Until End of Study (estimated up to 50 months))
- To assess the safety and tolerability of T-DXd with rilvegostomig vs T-DXd monotherapy(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 50 months))
- To evaluate the efficacy of T-DXd with rilvegostomig vs Standard of Care in terms of Overall Survival in the FAS (HER2 IHC 3+/2+) population(From date of randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized))
- To evaluate the efficacy of T-DXd monotherapy vs Standard of Care in terms of Overall Survival in the FAS (HER2 IHC 3+) population(From date of randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized))
- To evaluate the efficacy of T-DXd monotherapy vs Standard of Care in terms of Overall Survival in the FAS (HER2 IHC 3+/2+) population(From date of randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized))
- To further evaluate efficacy of T-DXd with rilvegostomig vs Standard of Care in terms of Progression Free Survival in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) 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 50 months))
- To further evaluate efficacy of T-DXd monotherapy vs Standard of Care in terms of Progression Free Survival in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) 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 50 months))
- To further evaluate the efficacy of T-DXd with rilvegostomig vs Standrad of Care in terms of objective response rate in the FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) 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 50 months))
- To further evaluate the efficacy of T-DXd monotherapy vs Standrad of Care in terms of objective response rate in the FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) 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 50 months))
- 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 FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) 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 50 months))
- 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 50 months))
- 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 FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) 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 50 months))
- To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of Overall survival in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations.(From date of randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized))
- To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of PFS in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations(From the date of randomisation until progression or death due to any cause, whichever occurs first (estimated up to 50 months))
- To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of Duration of response in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations(From the date of first response until progression or death due to any cause, whichever occurs first (estimated up to 50 months))
- To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of Objective response rate in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) 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 50 months))
- To assess the safety and tolerability of T-DXd with rilvegostomig vs Standard of Care(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 50 months))
- To assess the safety and tolerability of T-DXd monotherapy vs Standard of Care(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 50 months))
- 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 50 months))
- 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 50 months))
- To describe patient-reported tolerability of T-DXd with rilvegostomig in comparison to T-DXd monotherapy based on a summary of symptomatic AEs(Until End of Study (estimated up to 50 months))
- 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 50 months))
- 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 50 months))
- To assess the pharmacokinetics of T-DXd, total anti- HER2 antibody, DXd and rilvegostomig in serum(From the time of informed consent until 90 days after the last dose of T-DXd and rilvegostomig)
- 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)
- 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 50 months))
- 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 50 months))
- To assess the safety and tolerability of T-DXd with rilvegostomig vs T-DXd monotherapy(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 50 months))
- To describe patient-reported tolerability of T-DXd with rilvegostmog in comparison to T-DXd monotherapy based on overall side-effect bother(Until End of Study (estimated up to 50 months))
研究者
研究点 (275)
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