A Phase Ia/Ib, Open-Label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Preliminary Efficacy of BC3195 in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 148
- 试验地点
- 1
- 主要终点
- Determination of the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)
研究概览
简要总结
This is a phase Ia/Ib, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of BC3195 in subjects with locally advanced or metastatic solid tumors in whom standard treatment has failed (either due to disease progression or intolerance). This study will consist of two parts: Dose escalation (Part 1) and dose expansion (Part 2). Each part will include a screening period, a treatment period, and follow-up period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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.
排除标准
- •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
研究组 & 干预措施
Part 1: Phase 1a Dose Escalation
Participants will receive BC3195 administered as an intravenous infusion every 3 weeks (Q3W) or according to an alternative dosing regimen, as recommended by the safety monitoring committee (SMC). Multiple dose cohorts will be enrolled. Participants will be monitored for dose limiting toxicities (DLTs) during the DLT assessment period, lasting 21 days. The SMC will determine the recommended phase 2 dose (RP2D) to be administered in Part 2 based on the safety, tolerability, PK, and anti-tumor activity of BC3195
干预措施: BC3195 (Drug)
Part 2: Phase 1b Dose Expansion
Participants will receive BC3195 at the RP2D identified in Phase 1a. Approximately 3 to 4 expansion cohorts will be enrolled using a Simon's 2-stage design. Expansion cohorts will focus on tumor types that may derive benefit from BC3195 treatment, including head and neck squamous cell carcinoma (HNSCC), esophageal squamous cell carcinoma (ESCC), breast cancer (BC), non-small cell lung cancer (NSCLC), endometrial cancer (EMC), urothelial cancer (UC), colorectal cancer (CRC), ovarian cancer (OC), pancreatic cancer, and prostate cancer.
干预措施: BC3195 (Drug)
结局指标
主要结局
Determination of the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)
时间窗: Day 1 of treatment through 30 days after the last dose
Incidence of Dose Limiting Toxicities (DLTs)
时间窗: First 21 days of treatment
Incidence and Severity of All Adverse Events (AEs)
时间窗: Screening through 12 weeks after the last dose
次要结局
- Objective Response Rate (ORR)(Day 1 of treatment through 6 weeks after the last dose)
- Disease Control Rate (DCR)(Day 1 of treatment through 6 weeks after the last dose)
- Overall Survival (OS)(Patient consent until death Day 1 of dosing until the date of death from any cause assessed up to 100 months)
- Area under the curve (AUC) of BC3195(Day 1 of dosing through 21 days post last dose)
- Half-life (t 1/2) of BC3195(Day 1 of dosing through 21 days post last dose)
- Progression Free Survival (PFS)(Day 1 of treatment through 6 weeks after the last dose)
- Volume of distribution (Vd) of BC3195(Day 1 of dosing through 21 days post last dose)
- Clearance (CL) of BC3195(Day 1 of dosing through 21 days post last dose)
- Time to Progression (TTP)(Day 1 of treatment through 6 weeks after the last dose)
- Duration of Response (DoR)(Day 1 of treatment through 6 weeks after the last dose)
- Time to reach maximum concentration (Tmax) of BC3195(Day 1 of dosing through 21 days post last dose)
- Maximum concentration (Cmax) of BC3195(Day 1 of dosing through 21 days post last dose)
- Immunogenicity indicators(Day 1 of dosing through 30 days post last dose)