临床试验/NCT03657043

NCT03657043已完成2 期

Open Label Phase 2 Study of Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With a Safety Run-in of a Dose-Dense Regimen

Seagen Inc.37 个研究点分布在 6 个国家目标入组 98 人开始时间: 2019年3月20日最近更新: 2023年5月6日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方: Seagen Inc.
入组人数: 98
试验地点: 37
主要终点: Number of Participants With Dose-Limiting Toxicities (DLTs) (Safety Run-In Only)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This trial will study tisotumab vedotin to find out what its side effects are and to see if it works for platinum-resistant ovarian cancer (PROC). It will test different doses of tisotumab vedotin that are given at different times. It will also compare the side effects and ability to treat tumors of these different doses and schedules. In this study, there will be a safety run-in group of approximately 12 patients that will look at a dose-dense treatment schedule. In a dose-dense schedule, smaller doses are given more frequently. In addition to the safety run-in patients, there will be three groups in the study. One group will get tisotumab vedotin once every 3 weeks (21-day cycles). The two other groups will get tisotumab vedotin once a week for 3 weeks followed by 1 week off (28-day cycles).

详细描述

The study objectives are to evaluate the safety, antitumor activity, and pharmacokinetics of tisotumab vedotin (TV) administered every 3 weeks or on Days 1, 8, and 15 of every 4-week cycle (3Q4W) for patients with epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer that has relapsed within 6 months of the completion of platinum-based treatment and determined to be platinum resistant. All patients must have PROC and be eligible for single agent chemotherapy.

The safety run-in period will evaluate the safety of a weekly schedule. The highest dose level that is considered safe will be the recommended phase 2 dose (RP2D) and will be used in Part A. In Part A, participants will be randomized in a 1:1 ratio to receive tisotumab vedotin intravenously (IV) every 3 weeks (Q3W regimen) or the safety run-in RP2D on Days 1, 8, and 15 of every 4-week cycle (weekly regimen; 3Q4W) if a RP2D has been identified. Participants who enroll in Part B will receive tisotumab vedotin on Days 1, 8, and 15 of every 4-week cycle (weekly regimen) at a pre-specified dose level, if the dose level is considered safe and tolerable in the safety run-in period.

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

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

•Histologic documentation of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
•Safety run-in only: PROC. Patients may have received more than 1 prior systemic treatment regimen in the PROC setting.
•Part A and Part B only: Patients with PROC who have received 1 to 3 anticancer lines of therapy overall, including at least 1 line of therapy containing bevacizumab or biosimilar.
•Adjuvant ± neoadjuvant are considered 1 line of therapy.
•Patients may have received a PARP inhibitor or an immuno-oncology (IO) agent; any of these regimens are to be considered a line of therapy for the purposes of this study if not used as maintenance therapy.
•Maintenance therapy (including bevacizumab, PARP inhibitors and IOs) will be considered part of the preceding line of therapy and not to be counted as a new line of therapy.
•Any chemotherapy regimen change due to toxicity in the absence of disease progression is considered as part of the same line of therapy.
•Hormonal therapy will be not be counted towards the lines of therapy.
•Measurable disease according to RECIST v1.1 as assessed by the investigator
•An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
•Life expectancy of at least 3 months
•Able to provide fresh or archival tissue for biomarker analysis

排除标准

•Primary platinum-refractory disease, defined as disease progression within 2 months of completion of first line platinum-based therapy
•Patients with clinical symptoms or signs of gastrointestinal obstruction with the past 6 months or who currently require parenteral nutrition
•Hematological: Known past or current coagulation defects leading to an increased risk of bleeding, diffuse alveolar hemorrhage from vasculitis, known bleeding diathesis, ongoing major bleeding, or trauma with increased risk of life-threatening bleeding within 8 weeks of trial entry
•Cardiovascular: Clinically significant cardiac disease including uncontrolled hypertension, unstable angina, acute myocardial infarction with 6 months of screening, serious cardiac arrhythmia requiring medication, medical history of congestive heart failure, or medical history of decreased cardiac ejection fraction of <45%
•Ophthalmological: Active ocular surface disease at baseline or prior episode of cicatricial conjunctivitis or Stevens Johnson syndrome
•Prior treatment with MMAE-derived drugs
•Inflammatory bowel disease including Crohn's disease and ulcerative colitis
•Ongoing, acute, or chronic inflammatory skin disease
•Uncontrolled tumor-related pain
•Inflammatory lung disease requiring chronic medical therapy
•Grade 3 or higher pulmonary disease unrelated to underlying malignancy
•Uncontrolled pleural or pericardial effusions
•Grade >1 peripheral neuropathy
•Patients who are pregnant or breastfeeding

研究组 & 干预措施

Safety Run-In (3Q4W Schedule)

Experimental

28-day, 3 dose cycle

干预措施: tisotumab vedotin (Drug)

Part A: Tisotumab Vedotin

Experimental

21-day, single dose cycle

干预措施: tisotumab vedotin (Drug)

Part A: Tisotumab Vedotin (3Q4W Schedule)

Experimental

28-day, 3 dose cycle

干预措施: tisotumab vedotin (Drug)

Part B: Tisotumab Vedotin (3Q4W Schedule)

Experimental

28-day, 3 dose cycle

干预措施: tisotumab vedotin (Drug)

结局指标

主要结局

Number of Participants With Dose-Limiting Toxicities (DLTs) (Safety Run-In Only)

时间窗: Up to 28 days

Incidence of dose-limiting toxicity (DLT) was evaluated in participants enrolled in the Safety Run-In, who were followed for protocol-defined DLT events up to 28 days after the first dose of tisotumab vedotin.

Confirmed Objective Response Rate (ORR) (Part B)

时间窗: Up to 9.7 months

Proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator

次要结局

Number of Participants With Adverse Events (AEs) (Part B)(Up to 23.0 months)
Progression-free Survival (PFS) (Part B)(Up to 9.7 months)
Overall Survival (OS) (Part B)(Up to 23.0 months)
Incidence of Antitherapeutic Antibodies (ATA) (Part B)(Up to 6.9 months)
Pharmacokinetic (PK) Parameter: Antibody-Drug Conjugate (ADC) Maximum Concentration (Cmax) (Part B)(Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.)
PK Parameter: ADC Time of Cmax (Tmax) (Part B)(Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.)
PK Parameter: ADC Area Under Concentration-Time Curve (AUC) (Part B)(Cycle 1 Dose 1 AUC 7: Assessed from Cycle 1 Days 1 - 8 (predose). Cycle 1 Dose 3 AUC 7: Assessed from Cycle 1 Days 15 - 22. Cycle 1 Dose 3 AUC 14: Assessed from Cycle 1 Days 15 - Cycle 2 Day 1 (predose).)
Confirmed and Unconfirmed ORR (Part B)(Up to 9.7 months)
Cancer Antigen 125 (CA-125) Response Rate According to Gynecologic Cancer Intergroup (GCIG) Criteria (Part B)(Up to 10.1 months)
PK Parameter: MMAE Tmax (Part B)(Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.)
Overall Response According to the Gynecological Cancer Intergroup (GCIG) Combined RECIST and CA-125 Criteria (Part B)(Up to 10.1 months)
Duration of Response (DOR) (Part B)(Up to 8.3 months)
Disease Control Rate (DCR) (Part B)(Up to 3.0 months)
Time to Response (TTR) (Part B)(Up to 23.0 months)
PK Parameter: MMAE AUC (Part B)(Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.)
PK Parameter: Free Monomethyl Auristatin E (MMAE) Cmax (Part B)(Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.)
PK Parameter: MMAE Trough Concentration (Ctrough) (Part B)(Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.)
PK Parameter: Total Antibody (TAb) Cmax (Part B)(Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.)
PK Parameter: TAb Tmax (Part B)(Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.)
PK Parameter: TAb Area Under Concentration-Time Curve (AUC) (Part B)(Cycle 1 Dose 1 AUC 7: Assessed from Cycle 1 Days 1 - 8 (predose). Cycle 1 Dose 3 AUC 7: Assessed from Cycle 1 Days 15 - 22. Cycle 1 Dose 3 AUC 14: Assessed from Cycle 1 Days 15 - Cycle 2 Day 1 (predose).)

研究者

发起方

Seagen Inc.

申办方类型

Industry

责任方

Sponsor

研究点 (37)

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