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

Inclusion criteria

• Male or female patients ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• 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.
• 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)
• 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
• Life expectancy ≥ 3 months
• Subjects with adequate organ function
• 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.
• Patients voluntarily participate in the study and should provide a written informed consent.

Exclusion criteria

• Pregnant or lactating women
• Prior systemic anticancer treatment, including investigational agents, within 5 half-lives or 4 weeks before the first dose (whichever is shorter)
• 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
• Previously received allogeneic tissue/solid organ transplantation
• Patients who have received radiation therapy within 2 weeks prior to the start of study treatment or with a history of radiation pneumonitis.
• 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
• Active viral infection requiring systemic therapy during the screening period
• Clinically uncontrolled pericardial effusion, pleural effusion, or ascites at screening
• Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease
• 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])
• 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
• 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
• 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
• Subjects with any active infection that requires anti-infective therapy judged by the investigators
• Known hypersensitivity or delayed hypersensitivity reactions to the same class and/or any components of BC3195
• 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)
• Subjects are not suitable for participating the study judged by the investigators
• Subjects with poor compliance, who are unwilling to or unable to follow study procedures