A Phase I/II Study to Evaluate XNW34017 in Patients With Advanced or Metastatic Solid Tumor

Inclusion criteria

• Dose escalation phase: Subjects with advanced and/or metastatic malignant solid tumors who have failed standard treatment or lack effective standard treatment, and have histologically or cytologically confirmed diagnosis.
• Dose expansion phase, including but not limited to: Advanced and/or metastatic small cell lung cancer, prostate cancer, etc., with disease progression confirmed by histopathology, and failure in the following anti-cancer treatments:

Small cell lung cancer: Patients with small cell lung cancer who have progressed or relapsed after receiving at least two prior systemic treatment regimens.

Metastatic castration-resistant prostate cancer (mCRPC): Patients who have previously received treatment with enzalutamide or abiraterone and have experienced disease progression. At screening, serum testosterone should be at castration levels (≤ 50 ng/dL or ≤ 1.73 nmol/L). For patients who have not undergone bilateral orchiectomy, LHRHa therapy should be administered ≥ 4 weeks prior to the first dose of study treatment and continued throughout the study.

• The subject must be ≥ 18 years of age at the time of signing the informed consent.
• At least one measurable lesion according to RECIST 1.1 criteria (applicable to the backfill cohort and dose expansion phase).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
• The subject's organ function levels must meet the following requirements within 7 days prior to the first dose:

Absolute Neutrophil Count (ANC) ≥ 1.5×10^9/L, Platelet Count ≥ 100×10^9/L, Hemoglobin ≥ 90 g/L; Creatinine Clearance ≥ 60 ml/min (calculated using the Cockcroft-Gault formula) or Serum Creatinine (Cr) ≤ 1.5 times the upper limit of normal; Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels ≤ 2.5 times the upper limit of normal (ULN), for liver cancer/liver metastasis patients, AST/ALT should be ≤ 5×ULN; Total Bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN), for patients with Gilbert's Syndrome, Direct Bilirubin (DBIL) must be ≤ 2×ULN; International Normalized Ratio (INR) ≤ 1.2 (without anticoagulant treatment), Activated Partial Thromboplastin Time (APTT) ≤ 1.25×ULN; for subjects who have been on stable-dose anticoagulant therapy (e.g., warfarin) for ≥8 weeks, INR must be ≤3.

• Life expectancy ≥ 12 weeks.
• Female participants of childbearing potential must undergo a urine or serum pregnancy test within 7 days prior to starting the study medication, and the result must be negative. If the urine pregnancy test is positive or inconclusive, a serum pregnancy test must be performed.
• During the study and for 6 months after the last dose of the study drug, an effective, medically approved contraception method (e.g., intrauterine device, contraceptive pills, or condoms) must be used. For male participants with a female partner of childbearing potential, they must either be surgically sterilized or agree to use an effective contraception method during the study and for 6 months after the last dose of the study drug. Additionally, male participants must agree not to donate sperm throughout their study participation and for at least 6 months after their last dose of study drug.
• The participant has given informed consent and has signed the informed consent form, and is willing and able to comply with the study procedures required by the protocol.

Exclusion criteria

• Individuals who have had an allergic reaction to any component of the XNW34017.
• The washout period of prior antitumor treatments before the first study drug treatment is insufficient, defined as follows:

Chemotherapy, small molecule targeted therapy, or endocrine therapy < 2 weeks or 5 half-lives, whichever is shorter; Monoclonal antibody therapy < 3 weeks; Brain radiotherapy < 2 weeks, palliative radiotherapy < 2 weeks, curative radiotherapy < 4 weeks.

• Subjects with double primary malignant tumors, except for the specific cancer being studied in this trial and any previously cured local tumors: non-invasive basal cell carcinoma or squamous cell carcinoma, non-invasive superficial bladder cancer, and any other tumors with a complete remission (CR) lasting more than 5 years.
• Receiving a live vaccine within 4 weeks prior to the first study drug treatment. Note: Seasonal flu vaccines are generally inactivated vaccines and can be used; however, intranasal flu vaccines, which are live attenuated vaccines, are not permitted.
• Use of granulocyte colony-stimulating factor (G-CSF) or granulocyte/macrophage colony-stimulating factor within 1 week prior to the first study drug treatment, or use of pegylated G-CSF within 2 weeks prior to the first study drug treatment. Receiving blood transfusion treatment within 2 weeks prior to the first study drug treatment. Use of erythropoietin (EPO) or IL-11 within 1 week prior to the first study drug treatment.
• Subjects who have not yet recovered from the toxicity of prior anticancer treatments to CTCAE grade ≤ 1 or a stable condition, except for AEs that are not considered to pose a safety risk (e.g., hair loss).
• A history of intracranial arteriovenous malformation, cerebral aneurysm, or stroke (including transient ischemic attack within 1 month prior to screening, but excluding old cerebral infarction and asymptomatic cerebral infarction).
• Presence of any of the following hematologic risk factors:

Known coagulation defects leading to an increased risk of bleeding; Diffuse alveolar hemorrhage caused by vasculitis; Persistent major bleeding; Trauma resulting in an increased risk of life-threatening bleeding; A history of severe extracranial injury or intracranial surgery within 8 weeks prior to the start of the trial.

• Unable to provide tumor tissue samples for biomarker expression testing (for subjects unable to provide tissue samples, enrollment may be determined through consultation between the investigator and the sponsor).
• Presence of clinically significant cardiovascular or cerebrovascular diseases:History of unstable angina;Myocardial infarction within 6 months prior to screening;Underwent angioplasty or coronary stent treatment within 6 months prior to screening;History of congestive heart failure with New York Heart Association (NYHA) classification of 3 - 4;Baseline QTc interval abnormality (QTcF > 450 ms);Occurrence of ≥ grade 2 ventricular arrhythmia within 6 months prior to screening;Poorly controlled hypertension: systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg despite standard antihypertensive treatment;Presence of cardiac disease/history that results in left ventricular ejection fraction (LVEF) < 50%.