A Phase I Study to Evaluate the Safety, Tolerability, and PK of HLX43 in Advanced/Metastatic Solid Tumors

Inclusion Criteria:

1. Have a full understanding of the study content, process, and possible adversereactions before the study, and sign the informed consent form (ICF); voluntarilyparticipate in the study; be able to complete the study as per protocolrequirements;

2. ≥ 18 years and ≤ 75 years at the time of signing the ICF, male or female;

3. In phase Ia, enroll patients with histologically or cytologically confirmedadvanced/metastatic malignant solid tumors, who are refractory to standardtreatment, or for which no standard treatment is available; In phase Ib Cohort 1:enroll patients with histologically or cytologically confirmed advanced/metastaticNSCLC, who are refractory to standard treatment, or for which no standard treatmentis available (The standard treatment for squamous NSCLC is defined asplatinum-containing chemotherapy combined with immune checkpoint inhibitor [ICI].The standard treatment for non-squamous NSCLC with known EGFR mutations is definedas EGFR inhibitors and platinum-containing chemotherapy. The standard treatment forpatients with non-squamous NSCLC without EGFR mutations is defined asplatinum-containing chemotherapy combined with immune checkpoint inhibitor [ICI]therapy); Cohort 2: enroll patients with histologically or cytologically confirmedadvanced/metastatic TC, who are refractory to first line platinum based standardtreatment; Cohort 3: enroll patients with histologically or cytologically confirmedadvanced/metastatic NSCLC, who are refractory to standard treatment and docetaxeltreatment (The standard treatment for squamous NSCLC is defined asplatinum-containing chemotherapy combined with immune checkpoint inhibitor [ICI].The standard treatment for non-squamous NSCLC with known EGFR mutations is definedas EGFR inhibitors and platinum-containing chemotherapy. The standard treatment forpatients with non-squamous NSCLC without EGFR mutations is defined asplatinum-containing chemotherapy combined with immune checkpoint inhibitor [ICI]therapy); Cohort 4: enroll patients with histologically or cytologically confirmedstage IIIB, IIIC, or IV NSCLC that cannot be treated with surgery or radiotherapy;positive PD-L1 expression (PD-L1 positive is defined as TPS ≥ 1%; PD-L1 expressionis subject to the central laboratory result) and no EGFR sensitizing mutation orALK/ROS gene rearrangement; no previous systemic anti-tumor therapy for NSCLC (Patients who have received adjuvant or neoadjuvant therapy are allowed to beenrolled if the adjuvant/neoadjuvant therapy has been completed at least 6 monthsbefore the diagnosis of stage IIIB, IIIC, or IV NSCLC);

4. At least one measurable lesion as per RECIST 1.1 within 4 weeks prior to the firstadministration;

5. An ECOG performance status score of 0-1 within 7 days prior to the firstadministration;

6. Life expectancy > 3 months;

7. The following conditions must be met in terms of the time of the firstadministration of the investigational product: at least 28 days from the previousmajor surgery, medical device treatment, locoregional radiotherapy (except forpalliative radiotherapy for bone lesions), cytotoxic chemotherapy, immunotherapy, orbiological product therapy; at least 14 days from the previous small moleculetargeted drug therapy and previous hormone therapy; at least 7 days from theadministration of the traditional Chinese medicine for anti-tumor indications, orminor surgery; and recovery of treatment-induced AEs to grade ≤ 1 (CTCAE v5.0,except for alopecia);

8. Subjects who agree to provide archived tumor tissue specimens that meet the testingrequirements (either from the most recent surgery or biopsy, preferably within 2years) or agree to undergo a biopsy to collect tumor tissue for PD-L1 expressiontesting; Note: Formalin-fixed paraffin-embedded (FFPE) tumor samples (paraffinblocks or unstained sections, which must meet the quality control criteria fortesting) collected from sites not receiving radiotherapy during the most recentsurgery or biopsy at or after the diagnosis of malignant tumor and pathologicalreports of such specimens shall also be provided.

9. Adequate organ functions as confirmed by laboratory tests within 7 days prior to thefirst administration of the investigational product (no blood transfusions ortreatment with granulocyte colony-stimulating factor within 14 days prior to thefirst administration).

10. For patients with hepatocellular carcinoma, Child-Pugh score must be A;

11. Male and female subjects with child-bearing potential must agree to use at least onehighly effective contraception method during the study and within at least 6 months (at least 8 months for Japanese subjects) after the last administration of theinvestigational product; female subjects of childbearing age must have a negativepregnancy test within 7 days prior to enrollment.

Exclusion Criteria:

Subjects who meet any of the following criteria are not allowed to be enrolled:

1. Patients who have history of other malignant tumors within 2 years prior to thefirst administration, except for cured cervical carcinoma in situ or cutaneous basalcell carcinoma;

2. Patients who previously have immune-related adverse events (irAEs) ≥ grade 3 inimmunotherapy;

3. Patients who have history of (non-infectious) interstitial lung disease (ILD)requiring steroids, or current ILD, or suspected ILD that cannot be ruled out byimaging at screening;

4. Subjects who are known to have anaphylaxis to protein preparations/monoclonalantibodies or are allergic to any component in the formulation of theinvestigational product;

5. Patients who have active systemic infectious diseases requiring intravenousantibiotics within 2 weeks prior to the first administration of the investigationalproduct;

6. Subjects who have any poorly-controlled cardiovascular and cerebrovascular clinicalsymptoms or diseases, including but not limited to: (1) NYHA Class II or greaterheart failure or left ventricular ejection fraction (LVEF) < 50%; (2) unstableangina pectoris; (3) myocardial infarction or cerebrovascular accident within 6months (except for lacunar infarction, slight cerebral ischemia, or transientischemic attack); (4) poorly controlled arrhythmia (including QTc intervals ≥ 450 msfor males and ≥ 470 ms for females) (QTc intervals are calculated by Fridericia'sformula); (5) poorly-controlled hypertension (systolic blood pressure > 150 mmHgand/or diastolic blood pressure > 100 mmHg after active treatment);

7. Patients who have been assessed as unsuitable for inclusion by the investigator, dueto brain metastases, spinal cord compression, or cancerous meningitis with clinicalsymptoms, or uncontrolled brain or spinal cord metastases that have been evidenced;Note: Patients with asymptomatic or stable brain metastases, spinal cordcompression, or cancerous meningitis as judged by the investigator are allowed to beenrolled;

8. Patients with known active or suspected autoimmune diseases. Those withautoimmune-related hypothyroidism and receiving thyroid hormone replacement therapyand those with type 1 diabetes mellitus controlled with insulin therapy are eligibleto be enrolled;

9. Patients who have received systemic corticosteroids (prednisone > 10 mg/day or anequivalent dose of a similar drug) or other immunosuppressive agents within 14 daysprior to the first administration; Except for the following circumstances: patientstreated with topical, ocular, intra-articular, intranasal, and inhaledcorticosteroids; those with short-term use of corticosteroids for prophylaxis if acontrast agent is used;

10. Patients who have used potent inhibitors or inducers of CYP2D6 or CYP3A within 2weeks prior to the first administration;

11. Patients with active tuberculosis;

12. Patients who have history of immunodeficiency, including human immunodeficiencyvirus (HIV) infection or other acquired or congenital immunodeficiencies, or historyof organ transplantation;

13. Patients with active HBV or HCV infection or HBV/HCV co-infection; Note: Patientswho are HBsAg (+) and/or HBcAb (+) must undergo an HBV-DNA test and have a result of < 500 IU/mL, < 2500 copies/mL, or < ULN to be enrolled. Eligible subjects withdetectable HBV-DNA must agree to receive anti-hepatitis B virus nucleosidetreatment. Patients who are HCV antibody (+) must undergo an HCV-RNA test and have a result <ULN to be enrolled. Subjects with HBV/HCV co-infection shall be excluded (positive for HBsAg or HBcAband positive for HCV antibody)

14. Patients who have received live vaccines within 28 days prior to the firstadministration;

15. Pregnant or lactating women (for Japanese subjects, pregnancy includes situationswhere the investigator believes that the subject may be pregnant, and lactatingwomen can be enrolled in the study if breastfeeding is stopped, but breastfeedingcannot be resumed after receiving the study treatment);

16. Subjects who are not suitable for participating in this clinical study due to anyclinical or laboratory abnormalities or other reasons as assessed by theinvestigator.