First-in-human, Open-label, Multicenter, Phase I/IIa, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety and Preliminary Efficacy of BNT142 in Patients With CLDN6-positive Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- BioNTech SE
- 入组人数
- 73
- 试验地点
- 18
- 主要终点
- Occurrence of treatment emergent adverse events (TEAEs) including Grade ≥3, serious, or fatal TEAEs by causal relationship to study treatment
研究概览
简要总结
This study is an open-label, multicenter, Phase I/IIa, dose escalation, safety, and pharmacokinetics (PK) study of BNT142 followed by expansion cohorts in patients with Claudin 6 (CLDN6)-positive advanced tumors.
详细描述
Part 1 (Dose escalation) of this study is a first-in-human (FIH), open-label, dose escalation safety and PK study of BNT142 in patients with advanced/metastatic CLDN6-positive solid tumors.
Part 2 (Expansion) will be a Phase IIa proof-of-concept study in up to three expansion cohorts of CLDN6 positive advanced/metastatic ovarian cancer, non-small cell lung cancer (NSCLC) of non-squamous type, and testicular cancer patients who have progressed on or after last prior treatment.
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
- •NOTE: Other protocol defined Inclusion/
排除标准
- •For Part 1 and 2:
- •Histological or cytological documentation of a malignant solid tumor (via a pathology report) that is metastatic or unresectable.
- •CLDN6-positive tumor sample as assessed by central laboratory testing using a validated immunohistochemistry assay in formalin-fixed paraffin-embedded neoplastic tissues or alternatively from fresh tissue if archival tissue is unavailable. If archival tissue samples from several points of time are available, the most recent one is preferred.
- •Measurable disease per RECIST 1.1 (measurable per RECIST 1.1 or evaluable per GCIG criteria for ovarian tumors).
- •For Part 1 (Dose escalation):
- •Patients with advanced/metastatic ovarian (including fallopian tube and peritoneal), non-squamous NSCLC, endometrial, or testicular cancer, for whom there is no available standard therapy likely to confer clinical benefit, or the patient is not a candidate for such available therapy, or patients with not otherwise specified tumors (as confirmed by histological diagnosis), rare tumors (defined as those occurring in <15 out of 100,000 people each year as per National Cancer Institute guidelines) and cancers of unknown primary, not included in the pre-defined eligible tumor types (the last three upon approval by the medical monitor). Patients must have received all available standard therapies, including targeted therapies based on mutation status (per guidelines from the United States Food and Drug Administration [FDA], American Society of Clinical Oncology, European Society for Medical Oncology or local guidelines used at the site), and failed at least first line standard of care therapy prior to enrollment.
- •Key Exclusion Criteria:
- •Chemotherapy, or molecularly-targeted agents within 3 weeks or 5 half-lives (whichever is longer) of the start of study treatment; immunotherapy/monoclonal antibodies within 3 weeks of the start of study treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of study treatment.
- •Radiotherapy in the last 6 weeks prior to the first dose of BNT142 (excluding brain radiotherapy for which 3 weeks prior to the first dose of BNT142 is allowed). Previously irradiated tumor lesions cannot be considered as target lesions or non-target lesions in this study.
- •Concurrent systemic (oral or intravenous [IV]) steroid therapy >10 mg prednisone daily or its equivalent for an underlying condition apart from physiologic corticosteroid replacement therapy.
- •Major surgery within 4 weeks before the first dose of BNT
- •Ongoing or active infection requiring IV treatment with anti-infective therapy that has been administered less than 2 weeks prior to the first dose of BNT
- •Prior treatment with a CLDN6 targeting therapy.
- •Side effects of any prior therapy or procedures for any medical condition not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events v.5 Grade ≤1, except for anorexia, fatigue, hyperthyroidism, hypothyroidism, and peripheral neuropathy, which must have recovered to Grade ≤
- •Alopecia of any grade is allowed.
- •Current evidence of new or growing brain or leptomeningeal metastases during screening. Patients with known brain metastases may be eligible if they:
- •Had radiotherapy, surgery or stereotactic surgery for the brain metastases;
- •Have no neurological symptoms (excluding Grade ≤2 neuropathy);
- •Have stable brain metastasis on the computer tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing the informed consent form; and
- •Are not undergoing acute corticosteroid therapy or steroid taper.
- •Notes: Patients with central nervous system symptoms should undergo a CT scan or MRI of the brain to exclude new or progressive brain metastases. Spinal bone metastases are allowed, unless imminent fracture with cord compression is anticipated.
- •Pregnant or breastfeeding or planning to get pregnant within 6 months of the last dose of BNT142.
研究组 & 干预措施
BNT142
干预措施: BNT142 (Biological)
结局指标
主要结局
Occurrence of treatment emergent adverse events (TEAEs) including Grade ≥3, serious, or fatal TEAEs by causal relationship to study treatment
时间窗: From first dose to 60 days after the last dose of BNT142
Occurrence of dose reductions and discontinuation of BNT142 due to TEAEs
时间窗: From first dose to 60 days after the last dose of BNT142
Part 1: Occurrence of dose-limiting toxicities (DLTs) during the DLT evaluation period in the dose escalation
时间窗: Assessed during the DLT period, i.e., up to 5 weeks after first dose of BNT142
Part 2: Objective response rate (ORR)
时间窗: Up to 36 months after last patient last dose
ORR is defined as the proportion of patients in whom a confirmed complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and per Gynecological Cancer Intergroup (GCIG) criteria incorporating RECIST 1.1 and cancer antigen (CA)-125 for the ovarian cancer population is the best overall response.
次要结局
- Part 1: PK parameter: Area under the concentration-time curve in the dosing interval (AUC)(Pre-dose until 60 days after last dose)
- Part 1: PK parameter: Clearance (CL)(Pre-dose until 60 days after last dose)
- Part 1: PK parameter: Volume of distribution (Vd)(Pre-dose until 60 days after last dose)
- Part 1: PK parameter: Maximum observed concentration (Cmax)(Pre-dose until 60 days after last dose)
- Part 1: PK parameter: Time to maximum observed concentration (Tmax)(Pre-dose until 60 days after last dose)
- Part 1: PK parameter: Concentration prior to next dose (Ctrough)(Pre-dose until 60 days after last dose)
- Part 1: PK parameter: Minimum observed concentration (Cmin)(Pre-dose until 60 days after last dose)
- Part 1: PK parameter: Elimination half-life (t½)(Pre-dose until 60 days after last dose)
- Part 1: ORR(Up to 36 months after last patient last dose)
- Disease control rate (DCR)(Up to 36 months after last patient last dose)
- Duration of response (DOR)(Up to 36 months after last patient last dose)