NCT06225596
进行中（未招募）
2 期
A Randomized Open-Label Phase 2/3 Study of BT8009 as Monotherapy or in Combination in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)
概览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 956
- 试验地点
- 372
- 主要终点
- Cohort 1: Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) assessed by blinded central independent review (BICR)
概览
简要总结
This is a global, multicenter, randomized, open-label study, with an adaptive design. The main objective of the study is to measure the efficacy and safety of BT8009 (zelenectide pevedotin) as monotherapy and in combination with pembrolizumab in participants with locally advanced or metastatic urothelial cancer (UC). The study includes a dose selection phase followed by an adaptive design continuation. The study is comprised of 2 cohorts. Cohort 1 will include participants who have not received any prior systemic therapy for locally advanced or metastatic UC and are eligible to receive platinum-based chemotherapy, whereas Cohort 2 will include participants who have received ≥ 1 prior systemic therapy for locally advanced or metastatic UC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Life expectancy ≥ 12 weeks.
- •Measurable disease as defined by RECIST v1.
- •Histologically or cytologically confirmed locally advanced (unresectable) or metastatic UC of the renal pelvis, ureter, bladder, or urethra.
- •Archival or fresh tumor tissue comprising muscle-invasive UC or locally advanced or metastatic UC should be available for submission to central laboratory.
- •Negative pregnancy test for women of childbearing potential (WOCBP) (negative serum test at Screening and negative urine or serum test within 72 hours prior to the first dose).
- •Cohort 1: Previously Untreated: Eligible to receive platinum-based chemotherapy (either cisplatin- or carboplatin-based chemotherapy based on Investigator decision.
- •Cohort 1: Participants must not have received prior systemic therapy for locally advanced or metastatic UC with the following exceptions:
- •Prior local intravesical chemotherapy, local surgery when full resection is not achieved, local immunotherapy, and radiotherapy are permitted if completed at least 4 weeks prior to the initiation of study treatment and all acute toxicities have resolved.
- •Prior neoadjuvant/adjuvant chemotherapy or monomethyl auristatin E (MMAE)-based therapy with recurrence \>12 months from completion of therapy.
- •Prior neoadjuvant/adjuvant immune checkpoint inhibitor therapy with recurrence \>12 months from completion of therapy.
排除标准
- •Active keratitis or corneal ulcerations.
- •Requirement, while on study, for treatment with strong inhibitors or strong inducers of human cytochrome P450 3A (CYP3A) or inhibitors of P-glycoprotein (P-gp) including herbal- or food-based inhibitors.
- •Any condition requiring current treatment with high dose corticosteroids (\> 10 mg daily prednisone or equivalent).
- •Known hypersensitivity or allergy to any of the ingredients of any of the study interventions, or to MMAE.
- •Has not adequately recovered from recent major surgery (excluding placement of vascular access).
- •Receipt of live or attenuated vaccine within 30 days of first dose.
- •Cohort 1: Previously Untreated: Prior treatment with a checkpoint inhibitor (CPI) for any other malignancy within the last 12 months.
- •Cohort 2: Previously Treated: Received more than 1 prior platinum-based chemotherapy regimen for locally advanced or metastatic UC. This includes neoadjuvant/adjuvant platinum-based chemotherapy if recurrence occurred within 12 months of completing therapy.
- •Cohort 2: Prior treatment with enfortumab vedotin or any other MMAE-based therapy
研究组 & 干预措施
Cohort 1: BT8009 Arm 1
Experimental
Participants will receive BT8009 and a standard dose of pembrolizumab.
干预措施: Pembrolizumab (Drug)
Cohort 1: Arm 3
Active Comparator
Participants will receive Platinum-based combination chemotherapy +/- avelumab maintenance
干预措施: Gemcitabine + cisplatin Or carboplatin (Drug)
Cohort 2: BT8009 Arm 2
Experimental
Participants will receive BT8009.
干预措施: BT8009 (Drug)
Cohort 2: Arm 3: BT8009 (Not Recruiting)
Experimental
Participants will receive BT8009 and a standard dose of pembrolizumab.
干预措施: BT8009 (Drug)
Cohort 1: BT8009 Arm 1
Experimental
Participants will receive BT8009 and a standard dose of pembrolizumab.
干预措施: BT8009 (Drug)
Cohort 1: BT8009 Arm 2
Experimental
Participants will receive BT8009 and a standard dose of pembrolizumab.
干预措施: BT8009 (Drug)
Cohort 2: BT8009 Arm 1
Experimental
Participants will receive BT8009.
干预措施: BT8009 (Drug)
Cohort 1: BT8009 Arm 2
Experimental
Participants will receive BT8009 and a standard dose of pembrolizumab.
干预措施: Pembrolizumab (Drug)
Cohort 1: Arm 3
Active Comparator
Participants will receive Platinum-based combination chemotherapy +/- avelumab maintenance
干预措施: Avelumab (Drug)
Cohort 2: Arm 3: BT8009 (Not Recruiting)
Experimental
Participants will receive BT8009 and a standard dose of pembrolizumab.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Cohort 1: Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) assessed by blinded central independent review (BICR)
时间窗: Up to approximately 6 years
The time from randomization to date of first documentation of disease progression or death.
Cohort 2: Objective response rate (ORR) per RECIST 1.1 assessed by BICR
时间窗: Up to approximately 6 years
The time from randomization to date of first documentation of disease progression or death.
次要结局
- Cohort 2: PFS per RECIST v1.1 assessed by BICR(Up to approximately 6 years)
- Cohorts 1 and 2: Number of participants reporting adverse events (AEs) and Serious adverse events (SAEs)(Until 30 days post last dose, up to approximately 6 years)
- Cohorts 1 and 2: DCR per RECIST 1.1 assessed by Investigator(Up to approximately 6 years)
- Cohorts 1 and 2: PFS per RECIST v1.1 assessed by Investigator(Up to approximately 6 years)
- Cohorts 1 and 2: ORR per RECIST 1.1 assessed by Investigator(Up to approximately 6 years)
- Cohorts 1 and 2: Overall survival (OS) rate(Up to approximately 7 years)
- Cohorts 1 and 2: Duration of response (DoR) per RECIST 1.1 assessed by BICR(Up to approximately 6 years)
- Cohort 1: ORR per RECIST 1.1 assessed by BICR(Up to approximately 6 years)
- Cohorts 1 and 2: DoR per RECIST 1.1 assessed by Investigator(Up to approximately 6 years)
- Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in vital signs(Until the end of treatment, up to approximately 6 years)
- Cohorts 1 and 2: Disease control rate (DCR) per RECIST 1.1 assessed by BICR(Up to approximately 6 years)
- Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in Laboratory Results(Until the end of treatment, up to approximately 6 years)
- Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG)(Until the end of treatment, up to approximately 6 years)
- Cohorts 1 and 2: Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)(Until the end of treatment, up to approximately 6 years)
- Cohorts 1 and 2: Change from Baseline in Euroqol-5 Dimensions (EQ-5D) Questionnaire(Until the end of treatment, up to approximately 6 years)
研究者
研究点 (372)
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相关资讯
National Cancer Centre Singapore Launches 40 Clinical Trials Spanning Multiple Cancer Types- National Cancer Centre Singapore is currently conducting 40 active clinical trials across diverse cancer types including lung, breast, liver, bladder, and hematologic malignancies.
- The trials feature innovative treatment approaches including antibody-drug conjugates, CAR-T cell therapies, and combination immunotherapy regimens targeting various molecular pathways.
- Notable studies include Phase III trials of disitamab vedotin for HER2-positive urothelial carcinoma and tarlatamab for limited-stage small-cell lung cancer.
- The comprehensive trial portfolio demonstrates Singapore's commitment to advancing cancer research and providing patients access to cutting-edge experimental therapies.Zelenectidepevedotin Shows Promise in Metastatic Urothelial Carcinoma- Zelenectidepevedotin (BT8009) demonstrated a 45% overall response rate in patients with metastatic urothelial carcinoma who were naive to enfortumab vedotin.
- The Duravelo-1 trial also reported a clinical benefit rate of 61% with zelenectidepevedotin, suggesting potential for improved outcomes in this patient population.
- Median duration of response was 11.1 months, indicating a durable effect of zelenectidepevedotin in responding patients with metastatic urothelial carcinoma.
- The ongoing Duravelo-2 trial is further evaluating zelenectidepevedotin as monotherapy or in combination with pembrolizumab.Zelenectide Pevedotin Shows Promise in Urothelial Carcinoma Treatment- Zelenectide pevedotin, a novel bicycle toxin conjugate, targets Nectin-4 and is being evaluated for metastatic urothelial carcinoma.
- Early data from the Duravelo-1 trial show a 45% objective response rate in patients who had not received enfortumab vedotin.
- The ongoing Duravelo-2 trial is assessing zelenectide pevedotin as monotherapy and in combination with pembrolizumab.
- Researchers hope zelenectide pevedotin will offer a less toxic alternative to existing Nectin-4 targeted therapies.