A Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of BC3195 in Patients With Advanced or Metastatic Cancer

Eligibility Criteria

• 1. Male or female patients ≥ 18 years of age.
• 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• 3. Subjects with locally advanced or metastatic solid tumors confirmed by histology or cytology who have not benefitted from or are intolerant of available therapy(ies) associated with a reasonable likelihood to confer clinical benefit because of known CDH3 expression, including, albeit not limited to: HNSCC, ESCC, BC, NSCLC, EC, UC, CRC, OC, pancreatic cancer, and prostate cancer.
• 4. Agree to provide previously archived tumor tissue samples, or newly obtained core biopsy, or excisional biopsy of a previously unirradiated tumor lesion (formalin fixed, paraffin embedded tissue blocks)
• 5. Subjects with at least one measurable lesion according to RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• 6. Life expectancy ≥ 3 months
• 7. Subjects with adequate organ function
• 8. Men or women of childbearing potential must use a highly effective method of contraception during the study and continue to take contraception measures for 6 months after the last dose of the study drug.
• 9. Patients voluntarily participate in the study and should provide a written informed consent.
• 1. Pregnant or lactating women
• 2. Prior systemic anticancer treatment, including investigational agents, within 5 half-lives or 4 weeks before the first dose (whichever is shorter)
• 3. Subjects diagnosed with immunodeficiency within 7 days prior to the first dose of the study drug; or subjects who are receiving longterm systemic steroid therapy or any other form of immunosuppressive therapy
• 4. Previously received allogeneic tissue/solid organ transplantation
• 5. Patients who have received radiation therapy within 2 weeks prior to the start of study treatment or with a history of radiation pneumonitis.
• 6. Known active CNS metastases and/or cancerous meningitis. Subjects with previously treated brain metastases who meet the following conditions are permitted to participate in the study: radiologically stable, that is, repeat imaging shows no evidence of progression for at least 4 weeks, clinically stable, and no steroid therapy is required for at least 14 days prior to the first dose of study treatment
• 7. Active viral infection requiring systemic therapy during the screening period
• 8. Clinically uncontrolled pericardial effusion, pleural effusion, or ascites at screening
• 9. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease
• 10. Hypertension that cannot be well-controlled with medical treatment. Not well-controlled is defined as systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg (adjustment of hypertensive medication prior to study initiation is permitted, but the mean of the most recent three consecutive blood pressure records prior to study entry must be ≤150/90 mmHg \[with at least 2- minute interval between each measurement\])
• 11. Cardiovascular disease of clinical significance: Including New York Heart Association \[NYHA\] Class II-IV, congestive heart failure, second-degree or higher heart block, myocardial infarction within the past 3 months, unstable arrhythmia or unstable angina, marked QT interval prolongation (12-lead ECG showing baseline-corrected QTc interval \>480 ms), cerebral infarction within 3 months, or having received PTCA or CABG within 6 months
• 12. Subjects with active or chronic corneal disorders, with other active ocular conditions requiring ongoing therapy or with any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy
• 13. Grade 2 or higher peripheral neuropathy. Other toxicities caused by prior anti-tumor therapy has not recovered to ≤ grade 1 (per CTCAE 5.0) (except for alopecia, pigmentation, and other events judged by the Investigator to be tolerable) or the level specified by the inclusion/exclusion criteria in this study
• 14. Subjects with any active infection that requires anti-infective therapy judged by the investigators
• 15. Known hypersensitivity or delayed hypersensitivity reactions to the same class and/or any components of BC3195
• 16. Subjects who received strong CYP3A4 inhibitors and Strong CYP3A4 inducers within 14 days or 5 half-lives whichever is shorter, before the first dose (refer to Appendix 7 for a list of strong CYP3A4 inhibitors and inducers)
• 17. Subjects are not suitable for participating the study judged by the investigators
• 18. Subjects with poor compliance, who are unwilling to or unable to follow study procedures