A Clinical Study of SYS6041 Combination Therapy for Recurrent Ovarian Cancer

Official title

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

Overview

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

Detailed description

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.

Interventions

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

Primary outcome measures

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

Secondary outcome measures (10)

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

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07714668 · SYS6041-002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗