A Phase 1, Dose Escalation and Dose Optimization Study of the Safety, Tolerability, and Anti-tumor Activity of BND-35 Administered Alone and in Combination With Nivolumab or With Cetuximab in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 12
- 试验地点
- 5
- 主要终点
- Part 1: Incidence of TEAEs dose limiting toxicities (DLT)
研究概览
简要总结
This is an open-label, multicenter, dose escalation and dose optimization study designed to evaluate safety, tolerability and preliminary anti-tumor activity of BND-35 administered alone and in combination with nivolumab or with cetuximab. The study will enroll advanced cancer patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy. The study will be comprised of two parts - a dose escalation phase (Part 1) and a dose optimization (Part 2). Part 1 is comprised of three sub-parts: BND-35 administered alone (Sub-Part 1A), BND-35 administered in combination with nivolumab (Sub-Part 1B), and BND-35 administered in combination with cetuximab (Sub-Part 1C). Part 2 is composed of two sub-parts: a dose optimization part where up to two doses of BND-35 per indication are administered in combination with nivolumab or with cetuximab.
详细描述
Estimated Study Duration:
Dose Escalation (Part 1): Approximately 34 months. Dose Optimization/Expansion (Part 2): Approximately 24 months.
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
- •Patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy
- •Histologic confirmation of malignancy
- •Measurable disease per RECIST v1.1
- •Eastern Cooperative Oncology Group Performance Status (ECOG) of 0 or 1
- •Participants must have adequate organ function as defined by laboratory tests
- •Part 1: Following tumor types: Breast cancer, cholangiocarcinoma, colorectal cancer, adenocarcinoma or squamous cell carcinoma of the esophagus, gastric or gastroesophageal junction adenocarcinoma, squamous cell carcinoma of the head and neck, non-small cell lung cancer, melanoma, ovarian cancer, renal cell carcinoma, pancreatic adenocarcinoma, soft tissue sarcomas
排除标准
- •Active, known or suspected autoimmune disease
- •Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications
- •Brain or leptomeningeal metastases
- •Known history of positive test for HIV or known AIDS
- •Acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV)
- •Participants after solid organ or allogeneic hematopoietic stem cell transplant
- •History of life-threatening toxicity related to prior immune therapy
- •History of life-threatening toxicity related to prior cetuximab or other anti-epidermal growth factor receptor antibodies (for Sub-Part 1C)
- •Unstable or deteriorating cardiovascular disease within the previous 6 months
- •Any major surgery within 4 weeks of study drug administration
- •Prior immune therapy treatments, unless at least 4 weeks have elapsed from last dose
- •Cytotoxic/Non-cytotoxic anti-cancer agents, unless at least 4 weeks have elapsed from last dose
- •Use of other investigational drugs within 28 days
- •Prior treatment with immunoglobulin-like transcripts (ILT3)-targeting agents
- •Administration of a live attenuated vaccine within 28 days
研究组 & 干预措施
BND-35 Dose Escalation (Sub-Part 1A)
Accelerated titration followed by standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. BND-35 will be administered at escalating doses of 0.3 mg/kg to 20 mg/kg intravenously (IV), every 2 weeks (Q2W)
干预措施: BND-35 (Drug)
BND-35 in Combination with Cetuximab Dose Escalation (Sub-Part 1C)
Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. BND-35 will be administered at escalating doses of 3 mg/kg to 20 mg/kg intravenously (IV) every 2 weeks (Q2W). Cetuximab will be administered intravenously (IV) at a dose of 500 mg/m2, every 2 weeks (Q2W)
干预措施: BND-35 (Drug)
BND-35 in Combination with Nivolumab Dose Optimization (Sub-Part 2A)
BND-35 dose optimization in combination with nivolumab. The indications for the combination cohorts will be selected following completion of Part 1. Enrollment will start after the recommended dose(s) of BND-35 have been determined based on data from Sub-Parts 1A, 1B, and 1C. Nivolumab will be administered at a dose of 240 mg IV, every 2 weeks (Q2W).
干预措施: BND-35 (Drug)
BND-35 in Combination with Nivolumab Dose Escalation (Sub-Part 1B)
Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. BND-35 will be administered at escalating doses of 3 mg/kg to 20 mg/kg intravenously (IV) every 2 weeks (Q2W). Nivolumab will be administered at a dose of 240 mg IV, every 2 weeks (Q2W).
干预措施: BND-35 (Drug)
BND-35 in Combination with Cetuximab Dose Optimization (Sub-Part 2B)
BND-35 dose optimization in combination with cetuximab. The indications for the combination cohorts will be selected following completion of Part 1. Enrollment will start after the recommended dose(s) of BND-35 have been determined based on data from Sub-Parts 1A, 1B, and 1C. Cetuximab will be administered intravenously (IV) at a dose of 500 mg/m2, every 2 weeks (Q2W)
干预措施: BND-35 (Drug)
BND-35 in Combination with Nivolumab Dose Escalation (Sub-Part 1B)
Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. BND-35 will be administered at escalating doses of 3 mg/kg to 20 mg/kg intravenously (IV) every 2 weeks (Q2W). Nivolumab will be administered at a dose of 240 mg IV, every 2 weeks (Q2W).
干预措施: Nivolumab (Drug)
BND-35 in Combination with Cetuximab Dose Escalation (Sub-Part 1C)
Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. BND-35 will be administered at escalating doses of 3 mg/kg to 20 mg/kg intravenously (IV) every 2 weeks (Q2W). Cetuximab will be administered intravenously (IV) at a dose of 500 mg/m2, every 2 weeks (Q2W)
干预措施: Cetuximab (Drug)
BND-35 in Combination with Nivolumab Dose Optimization (Sub-Part 2A)
BND-35 dose optimization in combination with nivolumab. The indications for the combination cohorts will be selected following completion of Part 1. Enrollment will start after the recommended dose(s) of BND-35 have been determined based on data from Sub-Parts 1A, 1B, and 1C. Nivolumab will be administered at a dose of 240 mg IV, every 2 weeks (Q2W).
干预措施: Nivolumab (Drug)
BND-35 in Combination with Cetuximab Dose Optimization (Sub-Part 2B)
BND-35 dose optimization in combination with cetuximab. The indications for the combination cohorts will be selected following completion of Part 1. Enrollment will start after the recommended dose(s) of BND-35 have been determined based on data from Sub-Parts 1A, 1B, and 1C. Cetuximab will be administered intravenously (IV) at a dose of 500 mg/m2, every 2 weeks (Q2W)
干预措施: Cetuximab (Drug)
结局指标
主要结局
Part 1: Incidence of TEAEs dose limiting toxicities (DLT)
时间窗: Up to 21 days in Cycle 1
Incidence of TEAEs meeting protocol defined DLT criteria
Part 1: Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
时间窗: Through study completion, up to approximately 34 months
Adverse event (AE): any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of study drug, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent events were events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs.
Part 1: Proportion of patients who discontinued study treatment due to TEAEs
时间窗: Through study completion, up to approximately 34 months
Number of patients who discontinued study treatment due to TEAEs
Part 2: Objective Response Rate (ORR) per RECIST v1.1
时间窗: Through study completion, up to approximately 24 months
Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1
Part 2: Incidence of TEAEs and SAEs
时间窗: Through study completion, an average of 24 months
Adverse event (AE): any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of study drug, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent events were events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs.
次要结局
- Part 1: Area under the plasma concentration-time curve (AUC)(Through study completion, up to approximately 34 months)
- Part 1: Time of maximum observed serum concentration (Tmax)(Through study completion, up to approximately 34 months)
- Part 2: Progression Free Survival (PFS)(Through study completion, up to approximately 24 months)
- Part 2: PFS rate(At 3, 6, 9, and 12 months, and up to 24 months)
- Part 2: Duration of Response(Through study completion, up to approximately 24 months)
- Part 2: Maximum observed plasma concentration (Cmax)(Through study completion, up to approximately 24 months)
- Part 2: Serum concentration at the end of the dosing interval (Ctrough)(Through study completion, up to approximately 24 months)
- Part 2: Time of maximum observed serum concentration (Tmax)(Through study completion, up to approximately 24 months)
- Part 2: Incidence of anti-drug antibodies (ADA)(Through study completion, up to approximately 24 months)
- Part 1: Objective Response Rate (ORR) per RECIST v1.1(Through study completion, up to approximately 34 months)
- Part 1: Serum concentration at the end of the dosing interval (Ctrough)(Through study completion, up to approximately 34 months)
- Part 1: Incidence of anti-drug antibodies (ADA)(Through study completion, up to approximately 34 months)
- Part 1: Maximum observed plasma concentration (Cmax)(Through study completion, up to approximately 34 months)
- Part 1: Terminal elimination half-life (T1/2)(Through study completion, up to approximately 34 months)
- Part 2: Terminal elimination half-life (T1/2)(Through study completion, up to approximately 24 months)
- Part 2: Area under the plasma concentration-time curve (AUC)(Through study completion, up to approximately 24 months)