A Phase 1/2, Open-Label, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Preliminary Efficacy of BC3195 in Combination With Pembrolizumab in Participants With Locally Advanced or Metastatic Solid Tumors
概览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 111
- 试验地点
- 1
- 主要终点
- Number of partcipants with Dose Limiting Toxicities (DLTs)
概览
简要总结
This is a Phase 1/2, open-label, dose escalation and expansion study to assess the safety, pharmacokinetics, and preliminary efficacy of BC3195 in combination with pembroliaumab in participants with locally advanced or metastatic solid tumors.
详细描述
This is a Phase 1/2, open-label, dose escalation and expansion study to assess the safety, pharmacokinetics, and preliminary efficacy of BC3195 in combination with pembroliaumab in participants with locally advanced or metastatic solid tumors. This study consists of two parts: A dose escalation part (Part 1) and a dose expansion part (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
- Na
- 干预模型
- Single Group
- 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
- •Provide written informed consent.
- •Aged at least 18 years at the time of ICF signature.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 within 7 days prior to the first dose of study treatment.
- •Life expectancy of ≥ 3 months based on the Investigator's assessment.
- •Participants in Dose escalation part must meet the following criteria: Histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and have received, or been intolerant to, all treatment known to confer clinical benefit, including but not limited to: NSCLC, BC, HNSCC, ESCC, EMC, UC, CRC, OC, and prostate cancer. The sponsor or designee must approve eligibility for malignancies other than those specifically mentioned above.
- •Participants in Dose expansion part must meet one of the following criteria:
- •For NSCLC (cohort 1):
- •Participants have pathologically documented Stage IIIB, IIIC, or Stage IV NSCLC without actionable genomic alterations (AGA) based on the American Joint Committee on Cancer, Eighth Edition (Participants must have documented negative test results for EGFR and ALK genomic alterations and have no known genomic alterations in ROS1, NTRK, BRAF, MET exon 14 skipping, or RET) and meet one of the following criteria:
- •Locally advanced or metastatic NSCLC participants relapsed or refractory to at least 1 prior line of therapy including platinum-based chemotherapy in combination with or without anti-PD(L)1 antibody; OR
- •Locally advanced or metastatic NSCLC participants relapsed or refractory to at least 2 prior lines of therapy including anti-PD(L)1 antibody and platinum-based chemotherapy sequentially.
排除标准
- •Has received prior systemic anticancer treatment, including investigational agents, within 5 half-lives or 4 weeks prior to the first dose of study treatment (whichever is shorter). Has received Traditional Chinese Medication within 7 days prior to study treatment.
- •Participants who have received major surgery (defined as requiring general anesthesia and \>24-hour inparticipant hospitalization) within 4 weeks prior to the first dose of study treatment. Participant must have recovered adequately from complications from the intervention prior to starting study treatment.
- •Has received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis.
- •Note: Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- •Has had an allogeneic tissue/solid organ transplant.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
- •Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during the study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study treatment.
- •Has 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.
- •Active viral infection requiring systemic therapy during the screening period.
研究组 & 干预措施
BC3195 in Combination with Pembrolizumab
The study is divided into two phases: the dose escalation phase (Phase I): BC3195 (with 3 preset dose cohorts: 1.8mg/kg, 2.1mg/kg, 2.4mg/kg Q3W) combined with pembrolizumab (200mg Q3W) will be enrolled sequentially; the dose expansion (Phase II) phase: the recommended Phase 2 dose (RP2D) for BC3195 from the dose escalation phase combined with pembrolizumab (200mg Q3W) will be used in 4 cohorts (NSCLC / TNBC / HNSCC /others).
干预措施: BC3195 (Drug)
BC3195 in Combination with Pembrolizumab
The study is divided into two phases: the dose escalation phase (Phase I): BC3195 (with 3 preset dose cohorts: 1.8mg/kg, 2.1mg/kg, 2.4mg/kg Q3W) combined with pembrolizumab (200mg Q3W) will be enrolled sequentially; the dose expansion (Phase II) phase: the recommended Phase 2 dose (RP2D) for BC3195 from the dose escalation phase combined with pembrolizumab (200mg Q3W) will be used in 4 cohorts (NSCLC / TNBC / HNSCC /others).
干预措施: Pembrolizumab/KEYTRUDA® (Drug)
结局指标
主要结局
Number of partcipants with Dose Limiting Toxicities (DLTs)
时间窗: Throughout the dose escalation phase, an average of 1 year
The incidence of dose-limiting toxicity (DLT) at different doses of BC3195 combined with pembrolizumab in patients with locally advanced or metastatic solid tumors. DLT will be assessed at the end of Cycle 1.
Investigator-assessed Objective Response Rate (ORR) of BC3195 combined with pembrolizumab in participants with solid tumors
时间窗: Throughout the dose expansion phase, an average of 2.5 years
ORR (per investigator's assessment based on RECIST v1.1) defined as the proportion of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR).
次要结局
- To characterize the PK parameter Ctrough of BC3195(Through study completion, an average of 2.5 year)
- Investigator-assessed progression-free survival (PFS) of BC3195 combined with pembrolizumab in participants with solid tumors(Through study completion, an average of 2.5 years)
- Investigator-assessed disease control rate (DCR) of BC3195 combined with pembrolizumab in participants with solid tumors(Through study completion, an average of 2.5 years)
- Assessment of CDH3/PD-L1 expression level in tumor tissue and the correlation between the expression level and the efficacy of BC3195 combined with pembrolizumab.(Through study completion, an average of 3 year)
- Investigator-assessed duration of response (DOR) of BC3195 combined with pembrolizumab in participants with solid tumors(Through study completion, an average of 2.5 years)
- Overall survival (OS) of BC3195 combined with pembrolizumab in participants with solid tumors(Through study completion, an average of 3 years)
- Number of partcipants with treatment emergent adverse events (TEAEs)(Through study completion, an average of 3 year)
- Number of partcipants with treatment related adverse events (TRAEs)(Through study completion, an average of 3 year)
- Number of partcipants with serious adverse events (SAEs)(Through study completion, an average of 3 year)
- To evaluate the concentration-time data for BC3195, total antibody, and payload(Through study completion, an average of 2.5 year)
- To characterize the PK parameter AUC of BC3195(Through study completion, an average of 2.5 year)
- To Characterize the PK parameter Cmax of BC3195(Through study completion, an average of 2.5 year)
- Assessment of the number of participants who are Anti-Drug Antibody (ADA)-positive at any time and who have a treatment-emergent ADA(Through study completion, an average of 3 year)