A Study of DXC018 in Patients With Advanced Solid Tumors

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the protocol requirements.
2. Male or female, age ≥18 years old and ≤75 years old.
3. Participants with advanced malignancy confirmed by histology or cytology.
4. Participants with locally advanced or metastatic solid tumors that cannot be surgically removed who have experienced disease progression after standard therapy, or are currently ineligible for standard therapy, or in lack of standard treatment. (Standard therapy is defined as per domestic consensus guidelines \[where applicable\] or treatment aligned with current domestic medical practice).
5. At least one measurable lesion as defined by RECIST v1.1.
6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
7. Life expectancy ≥ 3 months.
8. Toxicities from prior anti-tumor therapy have recovered to Grade ≤1 as defined by NCI-CTCAE v5.0 (except alopecia or vitiligo). Participants with grade 2 toxicities per NCI-CTCAE v5.0 may be enrolled with no safety risks judged by the investigators (e.g., Grade 2 peripheral neuropathy).
9. Adequate organ function as defined by the following laboratory values:

Hematological:

1. Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L (No use of G-CSF or granulocyte-/white blood cell-boosting drugs within 7 days prior to the screening lab test).
2. Platelet count ≥ 90 × 10⁹/L (No platelet or whole blood transfusion or platelet-boosting drugs within 7 days prior to the screening lab test).
3. Hemoglobin (HGB) ≥ 90 g/L (No red blood cell (RBC) or whole blood transfusion or hemoglobin-boosting drugs within 7 days prior to the screening lab test).

Hepatic:

1. Total Bilirubin (TBIL) ≤ 1.5 × ULN (Upper Limit of Normal); except for participants with congenital bilirubinemia, e.g., Gilbert's syndrome (TBIL ≤ 3.0 × ULN).
2. AST and ALT ≤ 2.5 × ULN.
3. AST and ALT ≤ 5.0 × ULN in the presence of liver metastases.

Renal:

Creatinine Clearance (Ccr) ≥ 60 mL/min or Serum Creatinine (Cr) ≤ 1.5 × ULN. For participants with urinalysis showing urine protein ≥ 2+ at screening, a 24-hour urine protein quantification should be performed; participants with a 24-hour urine protein ≤ 1 g may be enrolled.

Coagulation:

1. International Normalized Ratio (INR) ≤ 1.5.
2. Activated Partial Thromboplastin Time (APTT) or Prothrombin Time (PT) ≤ 1.5 × ULN.

Cardiac:

Left Ventricular Ejection Fraction (LVEF) ≥ 50%. 10. Participants and their partners agree to use effective methods of contraception (excluding the rhythm method) from the time of signing the informed consent form until 6 months after the last dose of study drug.

Exclusion Criteria:

1. Participants with primary malignancies in other organs currently. Participants may be enrolled in the following scenarios: participants with healed basal cell or squamous cell skin cancer, cervical carcinoma in situ, papillary thyroid cancer, ductal carcinoma in situ of the breast.Or participants with other malignancies achieving over 5-year disease-free survival.
2. Serum pregnancy test: Positive or breastfeeding woman.
3. Received systemic anti-tumor therapy or investigational drug without washout. Received major surgeries treatment within 28 days prior to the first dose. Received local radiotherapy within 14 days prior to the first dose.
4. History of solid organ transplantation.
5. Participants with primary central nervous system (CNS) tumors or CNS metastases. With the following exceptions: asymptomatic and stable brain metastases, or participants who have not received steroid or other treatments for brain metastases ≥ 28 days.
6. History of grade 3 or higher allergic reactions to trastuzumab injection, pertuzumab injection, or similar biological products. History of allergy to any component or excipient of DXC018.
7. Evidence of severe or uncontrollable heart diseases that require treatments, including any of the following: Class III or IV heart failure defined by the New York Heart Association (NYHA) functional classification system. Uncontrollable unstable angina. History of myocardial infarction within 6 months prior to screening. Evidence of clinically significant arrhythmias except atrial fibrillation and paroxysmal supraventricular tachycardia.
8. QTcF interval ≥ 470 milliseconds (QT interval must be corrected using Fridericia's formula \[QTcF\]).
9. Uncontrolled severe hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg).
10. Received strong CYP3A4 inhibitors or inducers within 7 days prior to the first dose.
11. Participants with interstitial lung disease or history of non-infectious pneumonia who have received steroid treatments currently (except mild illness judged by investigators, including mild interstitial lung disease, stable radiation pneumonitis, or chronic pneumonitis) Other conditions which result in severe pulmonary function impairement.
12. Presence of severe unhealed wounds, ulcers, or fractures.
13. Participants who have an active infection requiring medication within 2 weeks before the first dose of the study drug.
14. Active hepatitis B (HBsAg positive and HBV DNA ≥ 500 IU/mL or ≥ 2000 copies/mL; active hepatitis C (HCV antibody positive and HCV RNA above the lower limit of detection).
15. HIV serology: positive; active syphilis (participants with only a positive syphilis antibody test may be enrolled).
16. Active bleeding within 30 days prior to screening, at risk of massive gastrointestinal bleeding judged by the investigators, hemoptysis, etc.. Or hereditary bleeding tendency or coagulation dysfunction. Or hemorrhagic symptoms requiring other medical intervention.
17. History of severe arterial/venous thrombotic events within 1 year prior to the first dose (except controllable stable low extremity deep venous thrombosis).
18. Participants who have the third gap fluids (like a large amount of pleural effusion, pericardial effusion, ascites, etc.) that cannot be controlled by drainage or other methods. and who need drainage to control the third gap fluids within 14 days before the first dose of the study drug.
19. Participants with more than 10 mg of prednisone or an equivalent dose of systemic corticosteroids, or other anti-inflammatory drugs with equivalent effects, or any form of immunosuppressive treatment within 2 weeks before the first dose of the study drug.
20. Administration of a live attenuated vaccine within 4 weeks prior to the first dose or planned vaccination during the study period.
21. Any other condition that, in the judgment of the investigator or sponsor, may affect the participant's participation in this study.