2023-503391-24-00招募中2 期
C5701002/SGN22E-002 - A study of enfortumab vedotin (ASG-22CE) as monotherapy or in combination with other anticancer therapies for the treatment of urothelial cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Seagen Inc.
- 入组人数
- 7
- 试验地点
- 3
- 主要终点
- Locally Advanced or Metastatic Urothelial Cancer ● Type, incidence, severity, seriousness, and relatedness of AEs ● Type, incidence, and severity of laboratory abnormalities
研究概览
简要总结
Locally Advanced or Metastatic Urothelial Cancer : ● To assess the safety and tolerability of enfortumab vedotin in combination with pembrolizumab and/or chemotherapy.
Randomized Cohort K: ● To assess the antitumor activity of enfortumab vedotin monotherapy or enfortumab vedotin in combination with pembrolizumab as measured by ORR per RECIST Version 1.1 by blinded independent central review (BICR).
Muscle Invasive Bladder Cancer: ● To assess the antitumor activity of neoadjuvant and perioperative enfortumab vedotin monotherapy or neoadjuvant enfortumab vedotin in combination with pembrolizumab as measured by the pathological complete response (pCR) rate, defined as the absence of viable tumor (pT0N0) in examined tissue from radical cystectomy (RC) and pelvic lymph node dissection (PLND) by central pathology review
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Histologically documented la/mUC, including squamous differentiation or mixed cell types.
- •Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Cohort G: Eligible for platinum-based chemotherapy (either cisplatin or carboplatin) and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months
- •Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Cohort K: Ineligible for cisplatin-based chemotherapy due to at least 1 of the following: Glomerular filtration rate (GFR) <60 mL/min and ≥30 mL/min, ECOG performance status of 2, NCI CTCAE Version 4.03 Grade ≥2 hearing loss, New York Heart Association (NYHA) Class III heart failure. No prior systemic treatment for locally advanced or metastatic disease. No adjuvant/neoadjuvant platinum-based therapy within 12 months prior to randomization.
- •Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Histologically confirmed MIBC with predominant >50% urothelial histology: Cohorts H and J: Clinical stage cT2-T4aN0M0; Cohort L: Clinical stage cT2-T4aN0M0 or cT1-T4aN1M0: Participants with pT1 disease are eligible only if they have N1 disease on imaging. Mixed cell types are eligible if urothelial cancer is predominant (>50%); Participants with plasmacytoid and/or neuroendocrine tumors are ineligible regardless of component percentage. Urothelial tumors not originating in the bladder (eg, upper tract tumors, urethral tumors) are ineligible.
- •Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Must be cisplatin-ineligible
- •Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Cohort-specific eligibility: Cohort J, H, and L: No prior systemic treatment, chemoradiation, or radiation therapy for MIBC. May have received prior intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for non-MIBC; Cohort J: Eligible for pembrolizumab.
- •Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: ECOG performance status of 0, 1, or
- •Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Anticipated life expectancy of ≥3 months.
- •Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Tumor samples with an associated pathology report from the diagnostic transurethral resection of a bladder tumor done 90 days prior to the first dose of study treatment must be available prior to enrollment and determined to be sufficient for pathology review and biomarker analysis.
- •Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Participants must be deemed eligible for RC+PLND.
- •Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2: Participants with ECOG performance status of 2 must meet the following additional criteria: hemoglobin ≥10 g/dL, GFR ≥50 mL/min, may not have NYHA Class III heart failure
- •Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K:Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, G and K Combination Arm).
- •Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Dose-escalation cohorts: Ineligible for first-line cisplatin-based chemotherapy and no prior treatment for la/mUC, or have disease progression following at least 1 platinum-containing treatment
- •Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Cohort A: Ineligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months
- •Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Cohort B: Must have disease progression during/following treatment with at least 1 platinum-containing regimen for la/mUC or disease recurrence
- •Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Cohort D: Eligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months
- •Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Cohort E: Ineligible for cisplatin-based chemotherapy, eligible for carboplatin, and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months
- •Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Cohort F: Ineligible for platinum-based chemotherapy, or disease progression during/following at least 1 prior treatment for la/mUC. Eligible for gemcitabine
排除标准
- •la/mUC - Cohorts A, B, D, E, F, G, and K: Received any prior treatment with a PD-1 inhibitor, PD-L1 inhibitor, or PD-L2 inhibitor, except Cohort F.
- •MIBC - Cohorts H, J, and L: Received any prior treatment with a CPI
- •MIBC - Cohorts H, J, and L: Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists.
- •MIBC - Cohorts H, J, and L: For participants in Cohort H, evidence of nodal disease on imaging. For participants in Cohort L, ≥N2 nodal disease on imaging.
- •MIBC - Cohorts H, J, and L: Participant has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC.
- •MIBC - Cohorts H, J, and L: Ongoing sensory or motor neuropathy Grade 2 or higher.
- •MIBC - Cohorts H, J, and L: Conditions requiring high doses of steroids or other immunosuppressive medications.
- •MIBC - Cohorts H, J, and L: Prior treatment with enfortumab vedotin or other MMAE-based ADCs for urothelial cancer
- •MIBC - Cohorts H, J, and L: Participants with a history of another invasive malignancy within 3 years before first dose of study drug.
- •la/mUC - Cohorts A, B, D, E, F, G, and K: Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, OX-40 agonists, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (except Cohort F).
- •la/mUC - Cohorts A, B, D, E, F, G, and K: Ongoing sensory or motor neuropathy Grade 2 or higher.
- •la/mUC - Cohorts A, B, D, E, F, G, and K: Active central nervous system (CNS) metastases.
- •la/mUC - Cohorts A, B, D, E, F, G, and K: Ongoing clinically significant toxicity (Grade 2 or greater) associated with prior treatment (including radiotherapy or surgery).
- •la/mUC - Cohorts A, B, D, E, F, G, and K: Conditions requiring high doses of steroids or other immunosuppressive medications.
- •la/mUC - Cohorts A, B, D, E, F, G, and K: Prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
- •la/mUC - Cohorts A, B, D, E, F, G, and K: Uncontrolled diabetes mellitus.
- •MIBC - Cohorts H, J, and L: Received prior systemic treatment, chemoradiation, and/or radiation therapy of muscle invasive bladder cancer.
结局指标
主要结局
Locally Advanced or Metastatic Urothelial Cancer ● Type, incidence, severity, seriousness, and relatedness of AEs ● Type, incidence, and severity of laboratory abnormalities
Locally Advanced or Metastatic Urothelial Cancer ● Type, incidence, severity, seriousness, and relatedness of AEs ● Type, incidence, and severity of laboratory abnormalities
Randomized Cohort K ● ORR (confirmed) per RECIST Version 1.1 by BICR
Randomized Cohort K ● ORR (confirmed) per RECIST Version 1.1 by BICR
Muscle Invasive Bladder Cancer ● pCR rate by central pathology review
Muscle Invasive Bladder Cancer ● pCR rate by central pathology review
次要结局
- ORR (confirmed) per RECIST Version 1.1 by investigator assessment
- DOR per RECIST Version 1.1 by BICR
- DOR per RECIST Version 1.1 by investigator assessment
- DCR per RECIST Version 1.1 by BICR
- DCR per RECIST Version 1.1 by investigator assessment
- PFS per RECIST Version 1.1 by BICR
- PFS per RECIST Version 1.1 by investigator
- OS
- Type, incidence, severity, seriousness, and relatedness of AEs
- Type, incidence, and severity of laboratory abnormalities
- Corresponding Additional/Exploratory Endpoints: Selected plasma or serum PK parameters of enfortumab vedotin, MMAE, and TAb
- Corresponding Additional/Exploratory Endpoints: Incidence of ATA to enfortumab vedotin
- Corresponding Additional/Exploratory Endpoints: Exploratory biomarkers of clinical activity, including relationship of Nectin-4 expression and PD-L1 expression status to response
- Corresponding Additional/Exploratory Endpoints: PFS2 by investigator assessment
- Corresponding Additional/Exploratory Endpoints: Change from baseline in PRO assessments of the EQ-5D-5L, EORTC QLQ-C30, and BPI-SF
- For the EV+Pembro arm: ORR (confirmed) per iRECIST by investigator assessment
- For the EV+Pembro arm: DOR per iRECIST by investigator assessment
- For the EV+Pembro arm: DCR per iRECIST by investigator assessment
- For the EV+Pembro arm: PFS per iRECIST by investigator assessment
- ORR (confirmed) per RECIST Version 1.1 by BICR
- EFS by BICR (Cohort L only)
- EFS by investigator assessment
- pDS rate by central pathology review
- DFS by BICR (Cohort L only)
- DFS by investigator assessment
- Percentage of planned RC+PLND delayed due to treatment-related AEs
研究者
Seagen Clinical Trial Information
Scientific
Seagen Inc.
研究点 (3)
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