2022-500030-28-00撤回2 期
A Phase 2 Multi-Cohort, Open-Label, Multi-Center Clinical Study Evaluating the Efficacy and Safety of Disitamab Vedotin (RC48-ADC) Alone and in Combination with Pembrolizumab in Subjects with Locally Advanced Unresectable or Metastatic Urothelial Carcinoma That Expresses HER2
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- Seagen Inc.
- 入组人数
- 68
- 试验地点
- 22
- 主要终点
- cORR (confirmed CR and confirmed PR) per RECIST v1.1 as assessed by BICR
研究概览
简要总结
To evaluate the efficacy as measured by cORR assessed by BICR for disitamab vedotin monotherapy in previously treated subjects with LA/mUC that expresses HER2 (HER2-positive [IHC 3+, or IHC 2+ and ISH-positive], and HER2-low [IHC 2+ and ISH-negative, or IHC 1+])
To evaluate the efficacy as measured by cORR assessed by BICR for disitamab vedotin alone and combined with pembrolizumab in treatment-naive subjects with LA/mUC that expresses HER2
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Expected survival ≥12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status score: Cohorts A and B: ECOG of 0 or 1 Cohort C: ECOG of 0, 1, or 2
- •Histologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra
- •Cohorts A and B: Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of platinum-containing chemotherapy Neoadjuvant or adjuvant systemic therapy, with progression within 12 months of completing last dose of therapy, is considered a line of prior therapy. Maintenance avelumab therapy delivered following first-line platinum therapy is not considered a separate line of therapy. Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first-line maintenance therapy or as second-line treatment is allowed
- •Cohort C: No prior systemic therapy for LA/mUC Neoadjuvant or adjuvant therapy, including PD-(L1) inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy
- •Cohorts A and B only: Radiographically documented disease progression during or after the most recent line of therapy for LA/mUC
- •At least one measurable lesion by investigator assessment based on RECIST version 1.
- •Cohort C only: Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation
- •Participants must be able to provide archived tumor tissue prior to treatment initiation. If archival tissue is not available, a baseline biopsy is required within 28 days of Cycle 1 Day
- •HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample
排除标准
- •Known hypersensitivity to disitamab vedotin, pembrolizumab (in Cohort C), or any of their components
- •Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study
- •Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
- •Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy
- •Major surgery that has not fully recovered within 4 weeks prior to dose administration
- •Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline
- •Other malignant tumors within 3 years of study treatment, except for: Prostate cancer treated with definitive intent (surgically or with radiation therapy) ≥ 1 year prior to treatment initiation is acceptable Malignancies that can be cured after treatment
- •There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.
结局指标
主要结局
cORR (confirmed CR and confirmed PR) per RECIST v1.1 as assessed by BICR
cORR (confirmed CR and confirmed PR) per RECIST v1.1 as assessed by BICR
cORR per RECIST v1.1 as assessed by BICR
cORR per RECIST v1.1 as assessed by BICR
次要结局
- Incidence of ADA against disitamab vedotin
- Incidence of ADA to pembrolizumab
- cORR per RECIST v1.1, as assessed by the investigator
- Confirmed DOR per RECIST v1.1, as assessed by BICR ● Confirmed DOR per RECIST v1.1, as assessed by the investigator
- PFS per RECIST v1.1, as assessed by BICR ● PFS per RECIST v1.1, as assessed by the investigator
- DCR (confirmed CR, confirmed PR, and stable disease) per RECIST v1.1, as assessed by BICR ● DCR per RECIST v1.1, as assessed by the investigator
- OS
- Type, incidence, relatedness, severity and seriousness of AEs ● Treatment discontinuations, dose reductions, or dose delays due to AEs ● Type, incidence and severity of laboratory abnormalities ● ECG abnormalities, including changes in QTc ● Effect on LVEF
- PK parameters of disitamab vedotin, free MMAE, and TAb
- PK parameters of pembrolizumab
研究者
Kevin Sokolowski
Scientific
Seagen Inc.
研究点 (22)
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