A Study of SYS6043 in Platinum-Resistant, Advanced Ovarian, Primary Peritoneal, or Fallopian Tube Cancers

A Randomized, Multicenter, Open-label, Phase 3 Clinical Trial Evaluating SYS6043 Versus Investigator's Choice Chemotherapy in Participants With Platinum-resistant Advanced Ovarian Cancer, Primary Peritoneal Cancer, and Fallopian Tube Cancer.

This is a randomized, open-label, multicenter Phase III clinical study designed to evaluate the efficacy and safety of SYS6043 versus investigator's choice chemotherapy in participants with platinum-resistant ovarian cancer, primary peritoneal, or fallopian tube cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Platinum-resistant Ovarian Cancer; Platinum-resistant Primary Peritoneal Cancer; Platinum-resistant Fallopian Tube Cancer
• Intervention / Treatment: Drug: SYS6043; Drug: Liposomal doxorubicin, paclitaxel, or topotecan

Detailed Description

This is a randomized, open-label, multicenter Phase III clinical study designed to evaluate the efficacy and safety of SYS6043 versus investigator's choice chemotherapy in participants with platinum-resistant ovarian cancer, primary peritoneal, or fallopian tube cancer. Approximately 460 eligible participants will be enrolled in the study.

Participants in the experimental group will receive SYS6043, administered on Day 1 of each cycle. Participants in the control group will receive investigator's choice chemotherapy:

Liposomal doxorubicin 40 mg/m² every 28 days (Q4W), administered on Day 1 of each cycle; Paclitaxel 80 mg/m² every 28 days (Q4W), administered on Days 1, 8, 15, and 22 of each cycle; Topotecan 4 mg/m² every 28 days (Q4W), administered on Days 1, 8, and 15 of each cycle.

Participants will continue to receive SYS6043 or investigator's choice chemotherapy until disease progression, unacceptable toxicity, withdrawal of consent, death, or until the Sponsor terminates the study (whichever comes first).

Tumor assessments based on RECIST v1.1, including radiological assessments by CT/MRI scans will be performed at Screening and subsequently every 6 weeks (± 7 days, + 7days for the first tumor assessment after Screening) from Cycle 1 Day 1 (C1D1) for the first 36 weeks then every 12 weeks (± 7 days) until disease progression, death, the start of new anticancer therapy, or participant's withdrawal of consent (whichever occurs first). Participants who discontinue treatment prior to disease progression shall continue to undergo tumor assessment until the first occurrence of any of the following: imaging-confirmed disease progression, death, loss to follow-up, withdrawal from the trial by the participant or their legal representative, initiation of new anti-tumor therapy, or completion of the entire trial.Imaging frequency as before.

All participants who discontinue SYS6043 or investigator's choice chemotherapy will be followed for survival every 2 months (± 7 days) until death, lost to follow-up, withdrawal of consent for survival follow-up, or end of study (EOS) (whichever comes first). Additional survival follow-up calls may occur periodically, if needed.

• Study Type: Interventional
• Enrollment (Estimated): 460
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: 031169085587; Email: ctr-contact@cspc.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female participants aged ≥ 18 years (as of the date of signed informed consent).
2. Histologically or cytologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a histologic subtype of high-grade serous carcinoma or G2-G3 endometrioid carcinoma.
3. Participants with prior platinum-based therapy and confirmed platinum-resistant recurrent disease, defined as disease progression or recurrence during platinum-based chemotherapy or within 6 months (183 days) after the last dose of platinum-based chemotherapy. No more than 1 line of systemic therapy following platinum-resistant recurrence, and a total number of treatment lines not exceeding 4 lines.
4. At least one evaluable extracranial lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
5. Expected survival of the participant is ≥ 3 months.
6. ECOG performance status 0-1, with no deterioration in ECOG score within 28 days prior to enrollment.
7. LVEF ≥ 50% as demonstrated by ECHO or MUGA obtained within 28 days before enrollment.

8. Major organ function must meet the following criteria within 7 days prior to enrollment:

   1. Complete blood count (no whole blood, red blood cell, or platelet transfusion, and no administration of hematopoietic growth factors [G-CSF or GM-CSF], erythropoietin [EPO], or thrombopoietin [TPO] to correct blood cell counts within 7 days before sampling):i. Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L;Platelet count (PLT) ≥ 100 × 10^9/L;Hemoglobin (HGB) ≥ 90 g/L.

   2. Blood biochemistry:i. Serum creatinine ≤ 1.5 × ULN;Serum total bilirubin (TBIL) ≤ 1.5 × ULN (participants with Gilbert's syndrome may be allowed up to 3 × ULN);Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5.0 × ULN for participants with hepatocellular carcinoma or liver metastasis);Serum albumin ≥ 30 g/L.

      3) Coagulation function: i. Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN (for participants not receiving anticoagulation therapy; for those on anticoagulation therapy, levels must be within the therapeutic range with stable dose).

10. Any toxicities related to prior therapy have resolved to CTCAE version 6.0 grade ≤1 or baseline level, excluding alopecia, fatigue, pigmentation, hypothyroidism stabilized with hormone replacement therapy, grade 2 peripheral neuropathy following chemotherapy, and other toxicities that the investigator deems not to pose a safety risk to participants.

11. A sufficient washout period from prior anti-tumor therapy is required prior to the first study drug administration.

12. Willing to provide a previously excised tumor sample or undergo a fresh tumor biopsy for the assessment of B7-H3 expression level (if no contraindications exist).

13. Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization.Female participants of childbearing potential must agree to use highly effective contraception during the study and for at least 7 months after the last dose of study drug.Females must not be breastfeeding during this period.Females must not donate oocytes or undergo oocyte retrieval for personal use during this period.

14. Provides voluntary written informed consent after adequate understanding of the clinical trial.

Exclusion Criteria:

1. Patients with platinum-refractory disease (progression within 1 month after the last platinum-containing therapy).
2. Prior treatment with B7H3-targeted therapy.
3. Prior treatment with irinotecan, topotecan, any other topoisomerase I inhibitor (including investigational TOP1 inhibitors), or topoisomerase inhibitor-antibody drug conjugate (e.g., trastuzumab deruxtecan, etc.).
4. Patients for whom paclitaxel, topotecan, and pegylated liposomal doxorubicin (as listed in the control group) are all considered inappropriate by the investigator.
5. History of severe cardiac or cerebrovascular disease, including but not limited to: heart failure ≥ New York Heart Association (NYHA) Class 2; acute coronary syndrome (e.g., myocardial infarction, unstable angina, etc.) within 6 months prior to screening; acute cerebrovascular disease (e.g., transient ischemic attack, cerebral infarction, cerebral hemorrhage, etc.) within 6 months prior to screening.
6. Mean corrected QT interval using the Fridericia formula (QTcF) > 470 milliseconds (ms) based on the results of three 12-lead electrocardiogram (ECG) examinations; history of serious cardiac arrhythmia (e.g., complete left bundle branch block, third-degree atrioventricular block, atrial fibrillation, atrial flutter, ventricular fibrillation, ventricular flutter, etc.), excluding transient atrial fibrillation and atrial flutter.
7. Unable or unwilling to discontinue concomitant medications known to prolong the QT interval.
8. A history of or current interstitial lung disease (ILD) requiring glucocorticoid treatment, non-infectious interstitial pneumonia, pulmonary fibrosis, and radiation pneumonitis requiring hormone treatment, or suspected of having such diseases by imaging examination at the time of screening.
9. A history of underlying lung diseases, including but not limited to pulmonary embolism within 3 months prior to the start of study treatment, severe asthma, severe COPD, restrictive lung disease, and other clinically significant lung damage or requiring supplementary oxygen.
10. Patients with active pulmonary tuberculosis (those who have received adequate treatment and stopped anti-tuberculosis treatment for ≥ 3 months before randomization may be enrolled).
11. Any autoimmune disease, connective tissue disease, or inflammatory disease involving the lungs that is recorded or suspected at the time of screening (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.).
12. Unstable thrombotic events requiring therapeutic intervention within 6 months prior to screening, such as deep vein thrombosis, arterial thrombosis, and pulmonary embolism (patients with stable lower extremity deep vein thrombosis, intermuscular venous thrombosis, or infusion-related thrombosis that are judged to be risk-free by the investigator may be included).
13. Presence of uncontrolled infection requiring intravenous antibiotics, antiviral drugs, or antifungal drugs.
14. Known human immunodeficiency virus (HIV) infection, or current active syphilis infection (i.e., positive treponema pallidum antibody (RPR or TRUST) or requiring systemic treatment).
15. Participants with active viral hepatitis (positive hepatitis B surface antigen and/or positive hepatitis B core antibody with HBV DNA ≥ 10000 copies/ml or 2000 IU/ml; positive hepatitis C virus (HCV) with HCV RNA above the lower limit of detection by the analytical method).
16. Presence of spinal cord compression or clinically active brain metastasis or meningeal metastasis. Participants with central nervous system metastases who have received prior central nervous system-directed therapy and have been radiologically and neurologically stable within 4 weeks before the first dose [i.e., imaging shows no new or enlarged metastatic lesions, no need for corticosteroid treatment or taking a stable or decreasing dose of corticosteroids (equivalent to ≤ 10 mg/day prednisone), and no symptoms] are eligible to enter the study. Untreated central nervous system metastases may be enrolled if the following conditions are met: no neurological symptoms, no need for surgery, radiotherapy, or corticosteroid treatment, and no obvious edema around the brain metastases.
17. Diagnosis of active malignant tumor within 3 years prior to randomization, except for the following cases: cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, and/or carcinoma in situ that has undergone radical resection, which the investigator deems eligible for enrollment.
18. Moderate or above pleural effusion, pericardial effusion, or ascites; if effusion drainage is performed (except for diagnostic thoracentesis), participants who have been stable for at least 2 weeks after drainage may be enrolled.
19. Presence of fistula diseases and perforation diseases such as genital fistula, genitourinary fistula, and enterovaginal fistula (if the perforation or fistula has been treated by resection or repair and the disease has recovered, enrollment is allowed).
20. Presence of intestinal obstruction, or signs and symptoms of intestinal obstruction, or requiring parenteral nutrition within 1 month prior to the start of study treatment; however, screening may be performed if surgical treatment has been performed and the obstruction is completely relieved; prior intestinal stent implantation with the intestinal stent still not removed by the screening period; gastrointestinal bleeding (including melena, hematochezia, etc.) within 1 month prior to randomization (those confirmed to have hemorrhoidal bleeding or only positive fecal occult blood may be enrolled); presence of abdominal abscess within 1 month prior to randomization.
21. Subjects who have received systemic administration of strong inhibitors or strong inducers of CYP3A4 and CYP2C8, or inhibitors of OATP1B1/OATP1B3 within 14 days prior to the first dose of study drug, or those who require continuous systemic use of such medicinal products during the study period.
22. Known allergy to the active ingredient or excipients of the study drug.
23. Having undergone autologous or allogeneic stem cell transplantation.
24. Subjects with a history of severe neurological or psychiatric disorders, including but not limited to dementia, depressive disorder, epileptic seizure, and bipolar disorder.
25. Have a history of drug abuse, or have any other medical conditions that, in the opinion of the Investigator, may increase the safety risk to the participant, or interfere with the participant's enrollment in and completion of the clinical study, or confound the evaluation of the study results.
26. Subjects planning to receive live vaccines or vaccinated with live vaccines within 28 days before the first dose of study drug.
27. Subjects with other severe physical conditions, clinically significant laboratory abnormalities, or poor treatment compliance, who may increase the risks of study participation, interfere with study outcomes, or are otherwise considered unsuitable for enrollment in this study by the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm; Participants will receive SYS6043	Drug: SYS6043; Participants in the experimental group will receive SYS6043, administered on Day 1 of each cycle.
Active Comparator: Active Comparator Arm; Participants will receive chemotherapy at investigator's discretion	Drug: Liposomal doxorubicin, paclitaxel, or topotecan; Participants in the control group will receive investigator's choice chemotherapy: Liposomal doxorubicin 40 mg/m² every 28 days (Q4W), administered on Day 1 of each cycle; Paclitaxel 80 mg/m² every 28 days (Q4W), administered on Days 1, 8, 15, and 22 of each cycle; Topotecan 4 mg/m² every 28 days (Q4W), administered on Days 1, 8, and 15 of each cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival by Blinded Independent Central Review (BICR) based on RECIST v1.1.	Time from randomization to time of objective radiographic disease progression as assessed by BICR based on RECIST v1.1 or death due to any cause.	From date of randomization to radiographic disease progression or death due to any cause, up to approximately 16 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Key secondary endpoint: Overall Survival	Time from randomization to the date of death due to any cause.	From date of randomization to death due to any cause, up to approximately 39 months.
ORR by Blinded Independent Central Review (BICR) based on RECIST v1.1.		up to approximately 24 months.
DoR by Blinded Independent Central Review (BICR) based on RECIST v1.1.		up to approximately 24 months.
DCR by Blinded Independent Central Review (BICR) based on RECIST v1.1.		up to approximately 24 months.
PFS by the investigator based on RECIST v1.1.		up to approximately 24 months.
ORR by the investigator based on RECIST v1.1.		up to approximately 24 months.
DoR by the investigator based on RECIST v1.1.		up to approximately 24 months.
DCR by the investigator based on RECIST v1.1.		up to approximately 24 months.
CA-125 response rate assessed by the investigator.	The GCIG CA-125 response is defined as at least 50% reduction in CA-125 levels from baseline. The response must have been confirmed and maintained for at least 28 days.	up to approximately 24 months.
Incidence of Adverse Events (AE) assessed by CTCAE 6.0.	An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment assessed by CTCAE 6.0. The investigator assesses the relationship of each event to the use of study drug.	up to approximately 39 months.
Number of Participants With Anti-Drug Antibodies (ADA).	Incidence, titer of anti-SYS6043 antibodies, and incidence of neutralizing antibodies (if applicable).	up to approximately 39 months.
Serum concentrations of toxin-bound antibody of SYS6043.		up to approximately 24 months.
Serum concentrations of total antibody of SYS6043.		up to approximately 24 months.

Collaborators and Investigators

• Sponsor: CSPC Megalith Biopharmaceutical Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: June 15, 2026
• First Submitted That Met QC Criteria: July 13, 2026
• First Posted (Actual): July 16, 2026

Study Record Updates

• Last Update Posted (Actual): July 16, 2026
• Last Update Submitted That Met QC Criteria: July 13, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Camptothecin; Alkaloids; Taxoids; Cyclodecanes; Diterpenes; Paclitaxel; Topotecan; liposomal doxorubicin
• Other Study ID Numbers: SYS6043-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No