A Phase 1 Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of STRO-002, an Anti-Folate Receptor Alpha (FolRα) Antibody-Drug Conjugate (ADC), in Patients With Advanced Epithelial Ovarian Cancer (Including Fallopian Tube or Primary Peritoneal Cancers) and Endometrial Cancers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 136
- 试验地点
- 27
- 主要终点
- Part 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-002)
研究概览
简要总结
Phase 1 trial to study the safety, pharmacokinetics and preliminary efficacy of STRO-002 given intravenously every 3 weeks.
详细描述
This study is a phase 1, open-label, multicenter, dose-escalation study with dose expansion to identify the maximum tolerated dose (MTD), the recommended phase 2 dose (RP2D) and to evaluate the safety, tolerability, and preliminary antitumor activity of STRO-002 in adult subjects with advanced epithelial ovarian cancer (EOC), including fallopian or primary peritoneal cancer, and endometrial cancer. Fallopian tube and primary peritoneal cancers are treated in the same manner as epithelial ovarian cancers and are thus included in this phase 1 study. Subjects enrolled in the study will be required to have progressive or recurrent disease after standard approved therapy as defined in the study eligibility criteria. The study has completed dose escalation and is currently in dose expansion, enrolling endometrial and ovarian cancer subjects.
All subjects enrolled on the study are required to have tumor tissue for determining folate receptor alpha (FolRα) expression levels, either from a prior surgery or tumor biopsy or from a biopsy performed during study screening. The testing for FolRα is done via an ICH assay. A minimum level of FolRα expression is required for enrollment for endometrial cancer but not for ovarian cancer.
Study drug, STRO-002, is administered by intravenous (IV) infusion on day 1 of 21-day cycles. Clinical evaluations and/or laboratory tests will be performed at a pre-specified schedule-weekly for cycles 1-4, and at the beginning of every cycle starting with cycle 5 as described in the schedule of assessments. Samples for PK analysis will occur at specific times on days 1, 8, and 15 of cycles 1 and 4, Day 1 of cycles 2, 3, and 5 and at the end of treatment (EOT) visit. The study requires imaging with a CT or MRI scan of the chest abdomen and pelvis at screening, every 6 weeks after enrollment for the first 18 weeks, then every 9 weeks, and at the end of treatment (EOT) visit. Additional X-rays may be required to confirm disease responses and per local institution standard of care.
Additional clinical evaluations and lab testing may occur at the discretion of the investigator.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- Female
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Measurable disease per RECIST 1.1
- •ECOG performance status (0-1)
- •Life expectancy > 3 months
- •Pathological confirmation of disease under study (historical information, diagnosis, pathology report, etc)
- •Expansion Cohorts A and C: High-grade serous EOC, fallopian tube cancer or primary peritoneal cancer
- •Expansion Cohort B: Histologically diagnosed epithelial endometrial cancer (endometrioid and serous adenocarcinomas; undifferentiated carcinoma; mixed epithelial carcinoma; or adenocarcinoma NOS)
- •Relapsed and/or progressive disease
- •Dose Expansion Cohorts A and C (Ovarian Cancer):
- •Platinum resistant and received 1-3 prior regimens or
- •Platinum sensitive and either:
- •Progressed after 2 prior lines of platinum therapy (regardless of platinum status)and received 2-3 prior regimens or
- •Progressed after 1 line of platinum therapy and 1 line of non-platinum therapy and received a total of 2-3 prior regimens if contraindicated to receive second platinum regimen.
- •Dose Expansion Cohort B (Endometrial Cancer):
- •Relapsed or progression after at least 1 platinum-based chemotherapy regimen or 1 immunotherapy-based regimen but not to exceed more than 3 prior regimens.
- •Fresh or archival tumor tissue samples
排除标准
- •Low grade (grade 1) ovarian carcinoma, clear cell, mucinous and sarcomatous ovarian carcinomas (Cohort A).
- •Endometrial carcinosarcomas, leiomyosarcoma and stromal sarcomas (Cohort B).
- •Prior treatment with a FolRα-targeting ADCs or FolRα-targeting vaccines
- •Platinum-refractory during frontline treatment (Cohorts A and C)
- •Greater than 3 lines of prior treatment
- •History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or to antibody-related fusion protein treatment
- •Preexisting clinically significant ocular disorders, clinically significant pre-exisiting ocular disorders, severe chronic obstructive pulmonary disease or asthma, clinically significant cardiac or cerebrovascular disease, or other significant concurrent, uncontrolled medical condition
- •Metastatic central nervous system or meningeal disease
- •Concurrent participation in another therapeutic treatment trial
研究组 & 干预措施
STRO-002 treatment
Dose Escalation: STRO-002 at increasing dose levels
Dose Expansion: STRO-002 at 4.3 mg/kg and 5.2 mg/kg
干预措施: STRO-002 (Drug)
结局指标
主要结局
Part 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-002)
时间窗: 18 months
Incidence of adverse events (AEs) observed across STRO-002 dose levels
Part 1: Define the recommended phase 2 dose (RP2D) of STRO-002
时间窗: 18 months
Frequency of dose-limiting toxicity and exposure across STRO-002 dose levels
Part 1: Define the maximum tolerated dose (MTD) of STRO-002
时间窗: 18 months
Frequency of dose-limiting toxicity and exposure across STRO-002 dose levels
Part 2: Evaluate preliminary anti-tumor activity (ovarian, Fallopian and primary peritoneal cancer patients)
时间窗: 24 months
Objective response rate per RECIST 1.1
Part 2: Evaluate preliminary anti-tumor activity (endometrial cancer patients)
时间窗: 24 months
Objective response rate per RECIST 1.1
次要结局
- Part 1: Assess the formulation of anti-drug antibodies to STRO-002(18 months)
- Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of duration of response (DOR) in patients treated with STRO-002(24 months)
- Part 2: Characterize the PK of STRO-002 by measuring the area under the plasma concentration versus time curve (AUC)(24 months)
- Part 2: Characterize the PK of STRO-002 by measuring the clearance (CL)(24 months)
- Part 1: Characterize the pharmacokinetics (PK) of STRO-002 by measuring the maximum plasma concentration (Cmax)(18 months)
- Part 1: Characterize the PK of STRO-002 measuring the total area under the concentration versus time curve from zero to infinity (AUCinf)(18 months)
- Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of progression-free survival (PFS) in patients treated with STRO-002(24 months)
- Part 2: Characterize the PK of STRO-002 by measuring the maximum plasma concentration (Cmax)(24 months)
- Part 1: Characterize the PK of STRO-002 by measuring the half-life (t1/2) of STRO-002(18 months)
- Part 1: Characterize the PK of STRO-002 by measuring the clearance (CL)(18 months)
- Part 1: Characterize the PK of STRO-002 by measuring the the steady state volume of distribution (Vss)(18 months)
- Part 2: Evaluate preliminary effect of STRO-002 treatment on CA-125 levels(24 months)
- Part 2: Further evaluate the incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-002)(24 months)