A Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile, and Preliminary Efficacy of SYS6043 ± Bevacizumab ± Chemotherapy in Participants With Advanced Solid Tumors

NCT07833735 | Not Yet Recruiting Phase 1

• 1 other identifier: SYS6043-003
• Study Type: interventional
• Target: 400
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multicenter, open-label, safety run-in, dose-expansion and cohort-expansion Phase I/II study designed to evaluate the safety, tolerability, PK profile and preliminary anti-tumor efficacy of SYS6043 (a B7-H3-targeted ADC) in participants with advanced/metastatic solid tumors. The trial consists of two phases: the Phase I component is the safety run-in study, and the Phase II component includes the dose-expansion study and cohort-expansion study.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (6)

• Incidence of dose-limiting toxicities (DLTs) -(Phase I: Safety Run-in Study)

  21 days for Arm 1-3.

• Incidence of adverse events (AEs) and serious adverse events (SAEs) assessed by CTCAE 6.0-(Phase I: Safety Run-in Study)

  2 years

• Maximum tolerated dose (MTD) (if any) ) of SYS6043 with or without bevacizumab with or without carboplatin-(Phase I: Safety Run-in Study)

  Up to 1year

• Recommended phase 2 dose (RP2D) of SYS6043 with or without bevacizumab with or without carboplatin-(Phase I: Safety Run-in Study)

  2 years

• Incidence of adverse events (AEs) and serious adverse events (SAEs) assessed by CTCAE 6.0-(Phase II: Dose-expansion Study)

  Up to 1year

• PFS rate assessed by RECIST Version 1.1(Phase II: Cohort-expansion Study)

  2 years

Secondary Outcomes (36)

• PFS based on RECIST v1.1-(Phase I: Safety Run-in Study)

  2 years

• ORR based on RECIST v1.1-(Phase I: Safety Run-in Study)

  2 years

• DoR based on RECIST v1.1-(Phase I: Safety Run-in Study)

  2 years

• DCR by Blinded Independent Central Review (BICR) based on RECIST v1.1-(Phase I: Safety Run-in Study)

  2 years

• TTR based on RECIST v1.1-(Phase I: Safety Run-in Study)

  2 years

Study Arms (5)

SYS6043+ bevacizumab

EXPERIMENTAL

In this group, participants will receive SYS6043 with bevacizumab;

Drug: SYS6043; Drug: bevacizumab

SYS6043+ carboplatin

EXPERIMENTAL

In this group, participants will receive SYS6043 with carboplatin

Drug: SYS6043; Drug: carboplatin

SYS6043 + carboplatin + bevacizumab

EXPERIMENTAL

In this froup, participants will receive SYS6043 with carboplatin and bevacizumab

Drug: SYS6043; Drug: bevacizumab; Drug: carboplatin

SYS6043

EXPERIMENTAL

In this group, participants will receive SYS6043 ;

Drug: SYS6043

Bevacizumab

EXPERIMENTAL

In this group, participants will receive bevacizumab ;

Drug: bevacizumab

Interventions

SYS6043 DRUG

Participants in the experimental group will receive SYS6043, Q3W administered on Day 1 of each cycle..

SYS6043; SYS6043 + carboplatin + bevacizumab; SYS6043+ bevacizumab; SYS6043+ carboplatin

bevacizumab DRUG

Participants in the experimental group will receive bevacizumab Q3W administered on Day 1 of each cycle.

Bevacizumab; SYS6043 + carboplatin + bevacizumab; SYS6043+ bevacizumab

carboplatin DRUG

Participants in the experimental group will receive carboplatin Q3W administered on Day 1 of each cycle.

SYS6043 + carboplatin + bevacizumab; SYS6043+ carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years (inclusive), as of the date of signing the Informed Consent Form (ICF).
• Phase I Safety Run in Cohort: Participants with solid tumors whose disease has relapsed or progressed during or following standard of care systemic therapy, or who are intolerant to standard of care therapy and for whom no available standard of care treatment exists.
• Phase II Dose expansion Stage: Participants with solid tumors whose disease has relapsed or progressed during or following standard of care systemic therapy, or who are intolerant to standard of care therapy and for whom no available standard of care treatment exists.
• Phase II Cohort Expansion Stage: Participants with histologically or cytologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, with histological subtypes of high grade serous carcinoma or grade 2 3 endometrioid carcinoma:
• Cohorts 1/2/3: Platinum sensitive recurrence (platinum sensitive recurrence is defined as disease progression or relapse ≥ 183 days after the last platinum containing chemotherapy).
• Cohort 1: Participants with platinum sensitive recurrence who achieved clinical complete response (CR) or partial response (PR) following platinum containing chemotherapy combined with bevacizumab. A minimum of 3 cycles of bevacizumab plus platinum based chemotherapy are required. For participants who have undergone interval secondary cytoreductive surgery, administration of only 2 cycles of bevacizumab during the final 3 cycles of second line platinum triplet therapy is permitted. If participants carry germline or somatic BRCA1/2 mutations, prior exposure to PARP inhibitors is required; alternatively, participants may have BRCA wild type or unknown BRCA status. The maximum interval between the last dose of prior triplet therapy (defined as Day 1 of the last cycle of second line platinum containing triplet combination therapy) and Cycle 1 Day 1 (C1D1) of maintenance therapy with bevacizumab or SYS6043 combined with bevacizumab shall be 10 weeks. No clinical evidence of disease progression (by physical examination, imaging, or CA 125) shall be present prior to trial randomization.
• Cohort 2: Participants with platinum sensitive recurrence who achieved clinical CR or PR following platinum containing chemotherapy without bevacizumab. If participants carry germline or somatic BRCA1/2 mutations, prior exposure to PARP inhibitors is required; alternatively, participants may have BRCA wild type or unknown BRCA status. The maximum interval between the last dose of prior triplet therapy (defined as Day 1 of the last cycle of second line platinum containing triplet combination therapy) and C1D1 of SYS6043 maintenance therapy shall be 10 weeks. No clinical evidence of disease progression (by physical examination, imaging, or CA 125) shall be present prior to trial randomization.
• Cohort 3: Participants with platinum sensitive recurrence who have not received prior systemic therapy.
• Cohort 4: First line treatment setting (no neoadjuvant therapy; newly diagnosed FIGO stage non I disease).
• Cohort 5: Participants who achieved CR/PR after first line platinum containing chemotherapy with bevacizumab; BRCA1/2 wild type / HRD negative or unknown status. The maximum interval between the last dose of prior triplet therapy (defined as Day 1 of the last cycle of first line platinum containing triplet combination therapy) and C1D1 of maintenance therapy shall be 10 weeks. No clinical evidence of disease progression (by physical examination, imaging, or CA 125) shall be present prior to trial randomization.
• At least one measurable extracranial target lesion per RECIST Version 1.1 (for Cohort 3 of Phase II only);
• Participant's expected survival ≥ 3 months;
• ECOG performance status 0-1 with no deterioration within 28 days prior to enrollment;
• LVEF ≥ 50% demonstrated by ECHO or MUGA performed within 28 days prior to enrollment;
• Adequate organ function as defined below, assessed within 7 days prior to enrollment:Major organ function must meet the following criteria within 7 days prior to enrollment:

You may not qualify if:

• Participants with non epithelial ovarian carcinoma, clear cell carcinoma, mucinous carcinoma, carcinosarcoma or sarcoma, mixed tumors containing any of the above histologic subtypes, or low grade / borderline ovarian tumors (Phase II expansion cohort only);
• Prior exposure to B7 H3 targeted therapy;
• Prior treatment with topoisomerase 1 inhibitor based antibody drug conjugates (e.g., trastuzumab deruxtecan);
• History of severe cardiac or cerebrovascular disease, e.g., heart failure with NYHA Class ≥ 2, acute coronary syndrome (e.g., myocardial infarction, unstable angina) within 6 months prior to screening, acute cerebrovascular events (e.g., transient ischemic attack, cerebral infarction, cerebral hemorrhage) within 6 months prior to screening;
• Mean QT interval corrected by Fredericia formula \> 470 ms based on three 12 lead ECG tracings; history of severe arrhythmias (e.g., complete left bundle branch block, third degree atrioventricular block, atrial fibrillation, atrial flutter, ventricular fibrillation, ventricular flutter; transient atrial fibrillation/atrial flutter excluded);
• Inability or unwillingness to discontinue concomitant medications known to prolong the QT interval;
• History of interstitial lung disease / non infectious pneumonitis requiring corticosteroid therapy (e.g., non infectious interstitial pneumonitis, pulmonary interstitial fibrosis, severe radiation pneumonitis), or active interstitial lung disease / non infectious pneumonitis at present, or radiological suspicion of such disease at screening;
• History of underlying pulmonary disease, including but not limited to pulmonary embolism within 3 months prior to study treatment initiation, severe asthma, severe chronic obstructive pulmonary disease (COPD), severe restrictive lung disease, other clinically significant pulmonary impairment, or requirement for supplemental oxygen;
• Presence of active pulmonary tuberculosis. Participants who have received adequate anti tuberculosis therapy and completed anti tuberculosis treatment for ≥ 3 months prior to randomization are eligible;
• Any autoimmune disease, connective tissue disease, or inflammatory disorder with documented or suspected pulmonary involvement at screening (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis);
• Thrombotic events requiring therapeutic intervention within 6 months prior to screening, including unstable deep vein thrombosis, arterial thrombosis, pulmonary embolism, myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack. Isolated muscular calf vein thrombosis or catheter related thrombosis may be enrolled if assessed as low risk by the Investigator;
• Uncontrolled infection requiring intravenous antibacterial, antiviral, or antifungal therapy;
• Known human immunodeficiency virus (HIV) infection; active syphilis infection (positive treponemal antibody or condition requiring systemic therapy);
• Participants with active viral hepatitis: positive hepatitis B surface antigen and/or positive hepatitis B core antibody with HBV DNA ≥ 10 000 copies/mL or 2000 IU/mL; positive HCV serology with HCV RNA above the lower limit of quantitation of the assay;
• Spinal cord compression, clinically active brain metastases, or leptomeningeal metastases. Participants with central nervous system (CNS) metastases are eligible if they have received prior CNS directed therapy and have radiologically and neurologically stable disease for at least 4 weeks before first study drug administration (i.e., no new or progressive metastatic lesions on imaging, no corticosteroid requirement, or stable/decreasing corticosteroid dose equivalent to ≤ 10 mg prednisone per day, and asymptomatic). Untreated asymptomatic CNS metastases are permitted if immediate intervention is not deemed necessary by the Investigator;

Sponsors & Collaborators

• CSPC Megalith Biopharmaceutical Co.,Ltd.: lead

MeSH Terms

Interventions

Bevacizumab; Carboplatin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals

Central Study Contacts

Clinical Trials Information Group officer

CONTACT

031169085587; ctr-contact@cspc.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: multicenter, open-label, safety run-in, dose-expansion and cohort-expansion Phase I/II study

Study Record Dates

• First Submitted: September 16, 2026
• First Posted: September 22, 2026
• Study Start (Estimated): October 15, 2026
• Primary Completion (Estimated): October 15, 2028
• Study Completion (Estimated): October 15, 2029
• Last Updated: September 22, 2026

Record last verified: 2026-09