Clinical Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SYS6045 in Patients With HER2-Positive, Expressing, or Mutated Advanced Malignant Solid Tumors

NCT07122063 | Active Not Recruiting Phase 1

• 1 other identifier: SYS6045-001
• Study Type: interventional
• Target: 266
• Locations: 1 country
• Sites: 1

Brief Summary

This study is the first-in-human (Phase I/II) trial of SYS6045, a multicenter, open-label, dose-escalation and dose-expansion clinical study. It aims to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary anti-tumor activity of SYS6045 in patients with HER2-positive, expressing, or mutated advanced solid tumors.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Dose-limiting toxicity (DLT)

  Up to 3 weeks

• Incidence and severity of AEs

  Up to 3 weeks

• Recommended Phase II Dose (RP2D)

  Up to 6 months

• Objective Response Rate (ORR)

  Up to 24 months

Secondary Outcomes (12)

• Objective Response Rate (ORR)

  Up to 24 months

• Disease Control Rate (DCR)

  Up to 24 months

• Progression-Free Survival (PFS)

  Up to 24 months

• Incidence and severity of AEs

  Up to 24 months

• Pharmacokinetic profile（AUC）

  Up to 24 months

Study Arms (1)

SYS6045

EXPERIMENTAL

SYS6045,Q3W

Drug: SYS6045

Interventions

SYS6045 DRUG

SYS6045, IV Q3W

SYS6045

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.
• ECOG Performance Status : 0-1.
• Tumor Lesion Requirements:
• Dose Escalation Phase: At least one evaluable lesions per RECIST v1.1. PK Expansion Phase and Phase II (Dose Expansion Study): At least one measurable lesion per RECIST v1.1.
• Life Expectancy: ≥3 months.
• Adequate Organ Function (confirmed by laboratory tests within 14 days prior to enrollment, without transfusion or hematopoietic growth factor support):
• Absolute Neutrophil Count (ANC) ≥1.5×10⁹/L Platelet Count (PLT) ≥100×10⁹/L Hemoglobin (Hb) ≥90 g/L Total Bilirubin (TBIL) ≤1.5×ULN (≤3×ULN for participants with liver metastases or hepatocellular carcinoma) ALT/AST ≤2.5×ULN (≤5×ULN for participants with liver metastases or hepatocellular carcinoma) Serum Creatinine (Cr) \<1.5×ULN Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN; International Normalized Ratio (INR) ≤1.5×ULN
• Left Ventricular Ejection Fraction (LVEF): ≥50% during screening.
• Fertile males or females must agree to use reliable contraceptive methods (hormonal contraceptives, barrier methods, or abstinence) with their partners during the trial and for ≥7 months after the last dose. Women of childbearing potential must have a negative blood pregnancy test within 7 days before enrollment.
• Histologically or cytologically confirmed advanced/unresectable, or metastatic solid tumors.
• HER2-positive, HER2-expressing, or HER2-mutated advanced solid tumors confirmed by a local laboratory (excluding lung cancer; HER2 positivity in lung cancer requires central laboratory confirmation). Prior failure of ≥1 line of standard therapy required.
• Note: Standard therapy is defined as treatment according to established guidelines, consensus, or clinical practice standards. Treatment failure is defined as disease progression or tumor recurrence/metastasis during or after therapy.
• Histologically or cytologically confirmed advanced/unresectable, or metastatic solid tumors.
• HER2-aberrant, HER2-expressing, or HER2-mutated advanced solid tumors confirmed by a local laboratory (Note: For lung cancer, HER2 genetic alterations may be accepted based on local reports, subject to sponsor review and approval. HER2 IHC/FISH testing for lung cancer requires central laboratory confirmation).
• Specific Criteria for Breast Cancer Cohort: Histologically or cytologically confirmed advanced/unresectable or metastatic breast cancer.

You may not qualify if:

• Prior treatment with HER2-targeted ADC carrying a topoisomerase I inhibitor payload (e.g., DS-8201) or other TOP1 ADCs (Patients who received such agents in the neoadjuvant/adjuvant setting and experienced recurrence ≥12 months after treatment completion may be enrolled)\[Applicable to: Phase I PK expansion and Phase II dose expansion studies\].
• Active neurological conditions, including: Spinal cord compression, clinically active brain metastases (untreated, symptomatic, or requiring corticosteroids/anticonvulsants for symptom control), carcinomatous meningitis or leptomeningeal disease. Asymptomatic CNS metastases with stable status ≥4 weeks after therapy and on tapering corticosteroids (≤10 mg/day prednisone equivalent) are allowed.
• Chronic immunosuppressive therapy, including: Long-term immunosuppressants (e.g., cyclosporine),Systemic corticosteroids (\>20 mg/day prednisone equivalent), Topical/nasal/inhaled corticosteroids are permitted.
• Unresolved toxicities from prior anticancer therapy Not recovered to CTCAE v5.0 Grade ≤1 or baseline levels(Alopecia, hyperpigmentation, or isolated lab abnormalities deemed non-risky by the investigator).
• Recent anticancer treatments (relative to first dose): Immunotherapy/macromolecular agents ≤4 weeks, Cytotoxic chemotherapy/small-molecule therapy ≤2 weeks, Traditional Chinese medicine ≤2 weeks.
• Strong CYP3A4 inducers/inhibitors or OATP1B1/1B3 inhibitors≤2 weeks before first dose, or Within 5 half-lives (whichever is longer).
• Major surgery or invasive procedures≤28 days before first dose Planned tumor resection during the study period.
• Known severe allergies to any component of the investigational drug, History of severe hypersensitivity to monoclonal antibodies (e.g., trastuzumab) .
• Active bacterial, fungal, or viral infections within 14 days prior to the first dose (Defined as requiring intravenous antimicrobial, antifungal, or antiviral therapy). Subjects without clinical manifestations of active infection prior to the first dose who are receiving prophylactic anti-infective treatment may be considered for enrollment.
• Uncontrolled serous cavity effusions requiring frequent drainage or medical intervention within 7 days prior to the first dose, includes pleural, peritoneal, or pericardial effusions necessitating additional intervention within 2 weeks post-drainage (excluding acellular cytological testing of exudates)
• History of immunodeficiency, including positive HIV antibody test.
• Active HBV or HCV infection: Active HBV: HBsAg-positive with HBV DNA\>2000 IU/mL，Active HCV: HCV-Ab-positive with HCV RNA\>upper limit of normal (ULN).
• History of non-infectious lung disease /pneumonitis requiring steroid therapy, current interstitial lung disease (ILD)/pneumonitis, or radiographically suspected ILD/pneumonitis during screening.
• Severe cardiovascular disease history, including but not limited to:
• Acute coronary syndrome within 6 months prior to the first dose.

Sponsors & Collaborators

• CSPC Megalith Biopharmaceutical Co.,Ltd.: lead

Study Sites (1)

The First Hospital of China Medical University

Shenyang, Liaoing, 024, China

Location

Study Officials

• Xiu Juan Qu, doctor

  First Hospital of China Medical University

  PRINCIPAL INVESTIGATOR

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: Eligible participants will receive SYS6045 via intravenous infusion on Day 1 of each treatment cycle. Cycles repeat every 3 weeks (Q3W, every 3 weeks).

Study Record Dates

• First Submitted: July 23, 2025
• First Posted: August 14, 2025
• Study Start: August 11, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2027
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)