HLX48-FIH101: A new targeted treatment called HLX48 for people with advanced or metastatic solid cancers.A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of HLX48 (EGFR/c-MET Bispecific Antibody-Drug Conjugate) in Participants With Advanced/Metastatic Solid Tumors

Exclusion

1. History of other malignant tumors within 2 years prior to first dose, except radically treated early-stage malignant tumors (carcinoma in situ or stage I tumors), such as cured cervical carcinoma in situ, non-melanoma skin cancer, ductal carcinoma in situ of the breast, and papillary thyroid carcinoma;
2. History of serious ocular diseases, including: (1) keratoconjunctivitis sicca; (2) severe keratopathy; (3) moderate or severe xerophthalmia;
3. History of (non-infectious) interstitial lung disease (ILD) requiring use of steroids, or current ILD, or suspected ILD that cannot be ruled out by imaging at screening;
4. Known history of severe allergic reactions to macromolecular protein preparations/monoclonal antibodies, or allergy to any component in the formulation of the investigational product; previous exposure to ADCs with topoisomerase I inhibitors as payload;
5. Active systemic infectious diseases requiring intravenous antibiotics within 2 weeks prior to the first dose of the investigational product;
6. Patients who have received systemic corticosteroids (prednisone > 10 mg/d or equivalent dose of similar drug) or other immunosuppressants within 2 weeks prior to randomization; Except: patients treated with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; short-term prophylactic use of corticosteroids for contrast agents, etc.;
7. Any poorly-controlled cardiovascular and cerebrovascular clinical symptoms or diseases, including but not limited to: (1) NYHA Class II or greater heart failure or left ventricular ejection fraction (LVEF) < 50%; (2) unstable angina pectoris; (3) myocardial infarction or cerebrovascular accident within 6 months (except lacunar infarction, slight cerebral ischemia, or transient ischemic attack); (4) poorly controlled arrhythmia (including QTc intervals ≥ 450 ms for males and ≥ 470 ms for females) (QTc intervals are calculated by Fridericia's formula); (5) poorly-controlled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg after active treatment); (6) pericarditis or uncontrolled pericardial effusion; (7) myocarditis;
8. Assessed as unsuitable for inclusion by the investigator, due to newly developed or clinically symptomatic brain or meningeal metastases, spinal cord compression, or cancerous meningitis, or uncontrolled brain or spinal cord metastases that have been evidenced;
9. Participants with known active or suspected autoimmune diseases. Participants with autoimmune-related hypothyroidism who are receiving thyroid hormone replacement therapy and those with type 1 diabetes mellitus controlled with insulin therapy are eligible to be enrolled;
10. Presence of unhealed skin lesions, including but not limited to (1) major traumatic injury within 4 weeks prior to the first dose (for paracentesis and other minor surgery, the investigator must confirm that the skin has healed prior to the first dose); (2) planned major surgery during treatment with the investigational product or within 6 months after the last dose;
11. Presence of uncontrollable pleural effusion or pericardial effusion after appropriate intervention, or ascites requiring repeated drainage (once a month or more frequently);
12. Use of strong inhibitors or inducers of CYP3A within 2 weeks prior to the first dose;
13. Patients with active tuberculosis;
14. Patients with a history of immunodeficiency, including human immunodeficiency virus (HIV)-positive or other acquired or congenital immunodeficiencies, or a history of organ transplantation;
15. Patients with active HBV or HCV infection or HBV/HCV co-infection;
16. Pregnant or lactating women;
17. Participants who are not suitable for participating in this clinical study due to any clinical or laboratory abnormalities or other reasons as assessed by the investigator.