A Clinical Study of SYS6041 Combination Therapy for Recurrent Ovarian Cancer

Официальное название

An Open-label , Multicenter, Multicohort, Phase II Clinical Study Evaluating the Efficacy and Safety of SYS6041 Combination Therapy for Recurrent Ovarian Cancer

Обзор

This is an open-label, multicenter Phase II clinical study conducted in subjects with recurrent ovarian cancer.

Подробное описание

The study aims to evaluate the safety/tolerability, pharmacokinetics, and preliminary efficacy of SYS6041 in combination with other agents in subjects with recurrent ovarian cancer.

Eligible subjects will receive SYS6041 in combination with different agents (carboplatin, paclitaxel, bevacizumab, enlonstobart) . Each treatment cycle lasting 3 weeks, until disease progression, intolerable toxicity, initiation of new anti-tumor therapy, withdrawal of informed consent, loss to follow-up, or death, whichever occurs first.

Вмешательства

• Препарат SYS6041, bevacizumab
  SYS6041: RP2D dose, ivgtt, Q3W Bevacizumab: 15mg/kg, ivgtt, Q3W
• Препарат SYS6041, carboplatin, bevacizumab
  SYS6041: RP2D dose, ivgtt, Q3W Carboplatin: AUC5, ivgtt. Q3W Bevacizumab: 15mg/kg, ivgtt, Q3W
• Препарат paclitaxel, carboplatin, bevacizumab
  Paclitaxel:175mg/m2, ivgtt, Q3W Carboplatin: AUC5, ivgtt. Q3W Bevacizumab: 15mg/kg, ivgtt, Q3W
• Препарат SYS6041, enlonstobart, bevacizumab
  SYS6041: RP2D dose, ivgtt, Q3W Enlonstobart:360mg, ivgtt, Q3W Bevacizumab: 15mg/kg, ivgtt, Q3W

Первичные конечные точки

• The incidence of dose-limiting toxicity (DLT) [Срок оценки: At the end of Cycle 1 (each cycle is 21 days)]
• AEs and SAEs [Срок оценки: Baseline up to 30 days post last dose]
• Recommended Phase 2 Dose (RP2D ) [Срок оценки: Up to approximately 3 years]
• Objective Response Rate (ORR) [Срок оценки: Up to approximately 3 years]

Вторичные конечные точки (10)

• Disease control rate (DCR) [Срок оценки: Up to approximately 3 years]
• Duration of Response (DoR) [Срок оценки: Up to approximately 3 years]
• Progression-Free-Survival (PFS) [Срок оценки: Up to approximately 3 years]
• Overall survival (OS) [Срок оценки: Up to approximately 3 years]
• Expression level of tumor markers [Срок оценки: Up to approximately 3 years]
• Maximum Plasma Concentration( Cmax) [Срок оценки: Up to approximately 3 years]
• Time to Maximum Plasma Concentration (Tmax) [Срок оценки: Up to approximately 3 years]
• Area Under the Serum Concentration Time Curve ( AUC) [Срок оценки: Up to approximately 3 years]
• Elimination half-life (t1/2) [Срок оценки: Up to approximately 3 years]
• Anti-Drug Antibody（ADA） [Срок оценки: Up to approximately 3 years]

Критерии участия

Критерии включения

• Fully understand this clinical trial and voluntarily sign the written informed consent form
• Age ≥ 18 years old
• Histologically or cytologically confirmed high-grade serous ovarian, epithelial fallopian tube carcinoma, and primary peritoneal cancer
• Cohort A and B：subjects with platinum-sensitive disease who have received ≤2 prior lines of systemic chemotherapy and if have a BRCAm or HRD-positive status must have recieved PARP inhibitor maintenance therapy; Cohort C: subjects with platinum-resistant disease who have received ≤3 prior lines of systemic chemotherapy
• Disease progression or intolerability with the most recent systemic anti-tumor treatment
• Adequate organ function with laboratory tests meeting criteria
• Have measurable disease per RECIST v1.1
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Expected survival ≥ 3 months
• Subjects of reproductive potential (males and females) must agree to use reliable contraceptive methods with their partner(s) throughout the trial period and for a minimum of 8 months following the last study drug administration

Критерии исключения

• Prior treatment with any topoisomerase I inhibitor-loaded ADC therapy
• History of other malignancies within 3 years before randomization/first dose or concurrent active malignancies (except cured localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, carcinoma in situ of the cervix, carcinoma in situ of the breast, etc., which are allowed to enroll)
• Subjects with active central nervous system (CNS) manifestations during the screening period, CNS metastases requiring corticosteroid therapy within 28 days prior to the first study drug administration, lesions involving the brainstem, or carcinomatous meningitis.
• Adverse reactions from prior anti-tumor therapy have not recovered to CTCAE 6.0 grade ≤ 1 (except for toxicities such as alopecia that researchers judge to have no safety risk)
• Major surgery within 28 days before randomization/first dose, or planned to undergo systemic or local tumor resection during the study period
• Subjects requiring folic acid supplementation during the screening period
• Subjects who have received strong CYP3A4 inhibitors or strong CYP3A4 inducers within 14 days prior to randomization/first study drug administration, or who require continuous systemic administration of such agents during the study treatment period
• History of severe gastrointestinal disease
• History of severe cardiovascular disease
• Uncontrolled serous effusions (e.g., pleural effusion, ascites, pericardial effusion) that necessitate frequent drainage or medical intervention within 14 days before randomization/first dose, or requirement for further intervention within 2 weeks after a previous intervention
• Subjects with a history of interstitial lung disease (ILD) or non-infectious pneumonia, current non-infectious pneumonia requiring corticosteroid treatment, or suspected ILD/non-infectious pneumonia identified at screening
• Active bacterial, fungal or viral infection within 14 days before randomization/first dose (defined as requiring intravenous anti-bacterial, anti-fungal or anti-viral drug therapy)
• Active hepatitis B or hepatitis C, defined as HBsAg positive and HBV DNA > 2000 IU/mL for active hepatitis B; defined as HCV-Ab positive and HCV RNA > ULN for active hepatitis C
• History of immunodeficiency or positive HIV antibody test during screening
• Presence of other conditions that may interfere with participants' participation in study procedures, not in line with participants' maximum benefit from participating in the study, or affect study results: such as history of mental illness, drug abuse or substance abuse, any other clinically significant disease or condition, etc.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07714668 · SYS6041-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗