First-In-Human Study in Subjects With Advanced or Metastatic Solid Malignant Tumors

Inclusion Criteria:

1. Be willing and able to provide signed informed consent form (ICF) for the trial.

2. Male or female, 18 years of age or older; willing and able to comply with studyrequirements.

3. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 with nodeterioration within 2 weeks of scheduled study treatment, and life expectancy ≥ 12weeks.

4. Must have a pathologically documented advanced/unresectable or metastatic solidmalignant tumor with HER-2 expression (IHC ≥ 1+) that is refractory to orintolerable with standard treatment, or for which no standard treatment isavailable.

5. Baseline measurable disease according to RECIST 1.1. Target lesions situated in apreviously irradiated area are considered measurable if progression has beendemonstrated in such lesions.

6. Adequate organ function assessed within 7 days prior to first trial treatment [hadnot received blood transfusion, erythropoietin (EPO), granulocyte colony stimulatingfactor (G-CSF) or other relevant medical support within 14 days before theadministration of the investigational product].

7. Have adequate treatment washout period before first trial treatment.

8. Have LVEF ≥ 50% by either echo cardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days prior to first trial treatment.

9. Female or male subjects of childbearing potential should be willing to use a highlyeffective method of contraception (with a failure rate of less than 1.0% per year)from first study treatment to 180 days after completion of the trial treatment.Female of childbearing potential should have a negative pregnancy test within 7 daysprior to first trial treatment (childbearing potential is defined as premenopausalfemales without documented tubal ligation or hysterectomy, or postmenopausal femaleswithin 1 year).

Exclusion Criteria:

1. Clinically active central nervous system (CNS) metastases, defined as untreated andsymptomatic, with following exceptions:

• Clinically stable through MRI/CT scans (at least 2 consecutive scans withinprior 6 months including 1 scan within 28 days prior to screening) and noprogressive or uncontrolled neurologic symptoms or signs (e.g., seizures,headaches, central nausea/emesis, progressive neurologic deficits, papilledema)for at least 4 weeks prior to the first treatment.

• Any untreated asymptomatic brain metastases not requiring immediate local orsystemic therapy (e.g., mannitol or corticosteroids).

• Leptomeningeal metastasis is excluded from the study entry.

2. Concurrent malignancy within 5 years prior to entry other than adequately treatedcervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cellcarcinoma, prostate cancer, thyroid cancer not requiring treatment, ductal carcinomain situ of the breast, or <T1 urothelial carcinoma.

3. Prior treatment with an antibody-drug conjugate (ADC) which consists of atopoisomerase I inhibitor derivative.

4. History of uncontrolled intercurrent illness including but not limited to:

• Active HBV or HCV infection. If HBsAg and HCV antibody positive, HBV DNA andHCV RNA assay should be performed. Subjects are eligible if HBV DNA ≤ 500 UI/ml (or 2000 copies/ml) or HCV RNA negative.

• Known HIV infection or known history of acquired immune deficiency syndrome (AIDS);

• Active tuberculosis infection.

• Active infection within 4 weeks prior to the first dose of trial treatment thatrequire the use of systemic antibiotics ≥ 7 days.

• Hypertension uncontrolled by standard therapies (not stabilized to 160/100mmHg);

• Clinically significant (that is, active) cardiovascular disease: cerebralvascular accident/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina pectoris (< 6 months prior toenrolment), congestive heart failure (New York Heart Association ClassificationClass II-IV) or serious cardiac arrhythmia requiring medication (includingcorrected QT interval prolongation of > 470 msec for women and > 450 for mencalculated according to Fridericia and/or pacemaker or prior diagnosis ofcongenital long QT syndrome;

• Serious nonhealing wound, ulcer or bone fracture.

5. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis thatrequired steroids or current ILD/pneumonitis, or where suspected ILD/pneumonitiscannot be ruled out by image at screening.

6. Previous severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infectioneither suspected or confirmed within 4 weeks prior to screening. Acute symptoms willbe excluded, or must have resolved and based on investigator assessment, there areno sequela that would place participant at a higher risk of receivinginvestigational treatment.

7. Subjects with ascites, pleural effusion, pericardial effusion which cannot becontrolled by appropriate interventions.

8. Have unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia, grade 2 hypoparathyroidism) related to prior anticancertherapy and stable anemia (i.e., untransfused Hb ≥ 9 g/dL without the need forsupportive transfusion within 2 weeks of screening) not yet resolved to grade ≤ 1 (NCI-CTCAEV5.0).

9. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenalreplacement doses ≤ 10 mg daily prednisone equivalents are permitted in the absenceof active autoimmune disease. A brief course of corticosteroids for the prophylaxis (e.g., contrast dye allergy) or treatment of non-autoimmune conditions (e.g.,delayed-type hypersensitivity reaction caused by contact allergen) is permitted.

10. History of life-threatening hypersensitivity or known to be allergic to proteindrugs or recombinant proteins or excipients in JSKN003 drug formulation.

11. Prior history of Herceptin induced anaphylaxis, angioedema, or severe hypotension.

12. Other conditions that, in the investigators' opinion, would make subjectsinappropriate to participate in this study, such as a history of mental illness,alcoholism or drug abuse.