An Open-label, Phase 1, First-in-human, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Maximum Tolerated or Administered Dose, Pharmacokinetics, Pharmacodynamics and Tumor Response Profile of the ILDR2 Function-blocking Antibody BAY1905254 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 60
- 试验地点
- 8
- 主要终点
- Incidence of treatment-emergent AEs (TEAEs) including treatment-emergent serious adverse events (TESAEs), adverse events of special interest (AESIs), and dose-limiting toxicities (DLTs)
研究概览
简要总结
This study is being done to learn more about a new drug called Bapotulimab given in combination with Pembrolizumab. The purpose of this study is to learn if this new combination of drugs is safe for the participants, how it affects the body and to try to find the best dose of the new drug to give to participants and to obtain a preliminary assessment of the tumor response efficacy in the recurrent or metastatic Head and Neck Cancer.
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 aged ≥ 18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Patients must have measurable disease (at least one unidimensional measurable lesion by Computed tomography [CT] or Magnetic resonance imaging [MRI]) per Response evaluation criteria in solid tumors (RECIST) 1.1, and following histologically confirmed, advanced or metastatic solid tumors:
- •Dose escalation: All solid tumor types with a likelihood of sensitivity to immunotherapy, as judged by the investigator.
- •Expansion of Bapotulimab in combination with pembrolizumab in Head and neck squamous cell carcinoma (HNSCC): recurrent or metastatic head and neck squamous cell carcinoma IO-naïve PDL1+/ CPS≥1(PD-L1: Programmed death ligand 1; CPS: Combined positive score).
- •Provision of archival tumor tissue at screening is mandatory for all patients in dose escalation.
- •For dose escalation, patients: must have received standard therapy or have no standard therapy available or patients have actively refused any treatment which would be regarded standard. Or in the opinion of investigator have been considered ineligible for a particular form of standard therapy on medical grounds.
- •Adequate bone marrow, liver and renal function.
- •Adequate cardiac function, measured by echocardiography.
排除标准
- •History of severe immune related adverse effects from prior immunotherapy (CTCAE v.5.0 Grade 4; CTCAE v.5.0 Grade 3 requiring treatment > 4 weeks), except hypothyroidism clinically stable on hormone replacement treatment and controlled type 1 diabetes.
- •Severe (CTCAE v.5.0 Grade ≥ 3) infections within 4 weeks before the first study drug administration, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia. Clinically active infections (CTCAE v.5.0 > Grade 1) within 2 weeks before the first study drug administration.
- •Previous or active myocarditis/myositis in history (independent of cause)
- •Active or history of autoimmune disease.
- •Known human immunodeficiency virus (HIV) infection.
- •Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
- •Treatment with systemic immunosuppressant medications within 2 weeks before the first study drug administration.
- •Ongoing or previous anti-cancer treatment or any immunostimulatory treatment including but not limited to interferons (IFNs), interleukin (IL)-2 and agonists for members of the tumor necrosis factor (TNF) receptor superfamily (e.g. 4-1BB) within 4 weeks before the first study drug administration.
- •For dose expansion cohort of Bapotulimab in combination with pembrolizumab in HNSCC: has progressive disease (PD) within six (6) months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.
研究组 & 干预措施
Dose escalation_Monotherapy
Patients with solid tumor types considered immunosensitive
干预措施: Bapotulimab (BAY1905254) (Drug)
Dose escalation_Combination therapy
Patients with solid tumor types considered immunosensitive
干预措施: Bapotulimab (BAY1905254) + Pembrolizumab (KEYTRUDA®) (Drug)
Expansion HNSCC_Combination therapy
Patients with head and neck squamous cell carcinoma (HNSCC)
干预措施: Bapotulimab (BAY1905254) + Pembrolizumab (KEYTRUDA®) (Drug)
结局指标
主要结局
Incidence of treatment-emergent AEs (TEAEs) including treatment-emergent serious adverse events (TESAEs), adverse events of special interest (AESIs), and dose-limiting toxicities (DLTs)
时间窗: Up to 58 months
Severity of treatment-emergent AEs (TEAEs) including treatment-emergent serious adverse events (TESAEs), adverse events of special interest (AESIs), and dose-limiting toxicities (DLTs)
时间窗: Up to 58 months
Cmax of Bapotulimab after first dose administration (Cycle 1) for cohorts receiving doses ≥ 20 mg
时间窗: Up to 504 hours after drug in Cycle 1
Maximum plasma concentration after single dose
AUC of Bapotulimab after first dose administration (Cycle 1) for cohorts receiving doses ≥ 20 mg
时间窗: Up to 504 hours after drug in Cycle 1
Area under the plasma concentration curve after single dose
Maximum tolerated dose (MTD) of Bapotulimab
时间窗: Up to 58 months
次要结局
- Incidence of positive anti-drug antibody titer for Bapotulimab(Up to 58 months)
- Best overall response rate(Up to 58 months)
- Recommended dose of Bapotulimab for Phase 2(Up to 58 months)
- Cmax,md after multiple dosing (Cycle 3) for cohorts receiving doses ≥ 20 mg(Up to 504 hours after drug in Cycle 3)
- AUC after multiple dosing (Cycle 3) for cohorts receiving doses ≥ 20 mg(Up to 504 hours after drug in Cycle 3)