A Phase II, multisite, open-label, single arm trial of BNT327 in combination with docetaxel in second-line stage IV or recurrent non-small cell lung cancer (NSCLC) following chemoimmunotherapy
概览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- BioNTech SE
- 入组人数
- 10
- 试验地点
- 5
- 主要终点
- Part 1: Occurrence of dose-limiting toxicities (DLTs) during the DLT-evaluation period by dose level. Time Frame: up to 21 days after first dose of investigational medicinal product (IMP).
概览
简要总结
To assess the safety and tolerability of BNT327 in combination with docetaxel (Part 1 and overall) in the trial population (participants with advanced/metastatic NSCLC which progressed after a first-line chemoimmunotherapy). To evaluate the efficacy of BNT327 with docetaxel in the trial population.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Have histologically or cytologically confirmed diagnosis of Stage IV NSCLC that has documented radiographic progression on one or after one prior line of systemic treatment (programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor and platinum-based chemotherapy concomitantly) in advanced/metastatic setting. Participants must have received a minimum 2 cycles of immunotherapy in first-line treatment to be eligible to this trial. Only 1 prior line of immunotherapy containing regimen is allowed in advanced/metastatic setting. If a participant had received adjuvant immunotherapy, the disease-free interval (after the last dose of adjuvant immunotherapy) should be at least 6 months. Historical PD-L1 results must be available. Patients with actionable genetic alterations are allowed to be enrolled if patients received locally approved and available targeted agent in combination with immunotherapy in first-line advanced/metastatic setting.
- •Have at least one measurable lesion as the targeted lesion based on response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been documented after irradiation. Historical images within 28 days of the screening visit may be accepted as a screening image if deemed acceptable in the opinion of the investigator.
- •Eastern cooperative oncology group performance (ECOG) status of 0 or
- •Adequate organ function.
排除标准
- •Known hypersensitivity to the study treatments, their metabolites or formulation of excipients including polysorbate 80 (see Docetaxel label).
- •Participants who received prior treatment with anti-vascular endothelial growth factor (VEGF) monoclonal antibody, or anti-PD-(L)-1/aVEGF bispecific antibody or docetaxel as monotherapy or in combination with other agents.
- •Have received more than one prior lines of therapies in advanced/metastatic setting.
- •Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 14 days prior to the initiation of study treatment (except for docetaxel premedication).
- •Have uncontrolled hypertension or poorly controlled diabetic conditions prior to study treatment.
- •Have a serious non-healing wound, ulcer, or bone fracture. This includes history (within 6 months prior to study entry) or risk of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra abdominal abscess or esophageal and gastric varices, or acute gastrointestinal bleeding. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation.
- •Participants with evidence of major coagulation disorders or other significant risks of hemorrhage.
- •Have superior vena cava syndrome or symptoms of spinal cord compression.
结局指标
主要结局
Part 1: Occurrence of dose-limiting toxicities (DLTs) during the DLT-evaluation period by dose level. Time Frame: up to 21 days after first dose of investigational medicinal product (IMP).
Part 1: Occurrence of dose-limiting toxicities (DLTs) during the DLT-evaluation period by dose level. Time Frame: up to 21 days after first dose of investigational medicinal product (IMP).
Part 1 and Part 2: Occurrence of BNT327 treatment-emergent adverse events (TEAEs), treatment-related TEAEs, treatment-emergent serious adverse events (TESAEs), treatment-related serious adverse events (TRSAEs), and adverse events of special interest (AESIs) graded according to the (US) National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Time Frame: from initiation of the first dose of IMP to the 90-day Follow-Up visit.
Part 1 and Part 2: Occurrence of BNT327 treatment-emergent adverse events (TEAEs), treatment-related TEAEs, treatment-emergent serious adverse events (TESAEs), treatment-related serious adverse events (TRSAEs), and adverse events of special interest (AESIs) graded according to the (US) National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Time Frame: from initiation of the first dose of IMP to the 90-day Follow-Up visit.
Part 1 and Part 2: Occurrence of dose interruption, dose reduction, and/or participant discontinuation due to adverse events (AEs). Time Frame: from initiation of the first dose of IMP until the 90-day Safety Follow-up visit.
Part 1 and Part 2: Occurrence of dose interruption, dose reduction, and/or participant discontinuation due to adverse events (AEs). Time Frame: from initiation of the first dose of IMP until the 90-day Safety Follow-up visit.
Part 1 and Part 2: Objective response rate (ORR) defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR per RECIST v1.1 based on investigator’s review is observed as best overall response). Time Frame: Up to approximately 2 years.
Part 1 and Part 2: Objective response rate (ORR) defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR per RECIST v1.1 based on investigator’s review is observed as best overall response). Time Frame: Up to approximately 2 years.
次要结局
- Part 1 and Part 2: Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST v1.1 based on the investigator’s assessment) to first occurrence of objective tumor progression (progressive disease, per RECIST v1.1 based on the investigator’s assessment) or death from any cause, whichever occurs first. Time Frame: Up to approximately 2 years.
- Part 1 and Part 2: Progression-free survival (PFS) based on the investigator’s assessment defined as the time from first dose of IMP to the first objective tumor progression (progressive disease per RECIST v1.1) or death from any cause, whichever occurs first. Time Frame: Up to approximately 2 years.
- Part 1 and Part 2: Depth of Response: Defined as the maximum percent reduction from baseline in tumor size measured by sum of target lesion diameter. Time Frame: Up to approximately 2 years.
- Part 1 and Part 2: Disease Control Rate (DCR) defined as the proportion of participants with confirmed CR, confirmed PR, or stable disease (per RECIST v1.1 based on the investigator’s assessment) as best overall response. Time Frame: Up to approximately 2 years.
- Part 1 and Part 2: Time to Response (TTR) defined as the time from first dose of IMP to first objective response (CR or PR per RECIST v1.1 based on the investigator’s assessment). Time Frame: Up to approximately 2 years.
- Part 1 and Part 2: Overall Survival (OS) defined as the time from first dose of IMP to death from any cause. Time Frame: Up to approximately 2 years.
- Part 1 and Part 2: Pharmacokinetic (PK) assessment: Maximum concentration (Cmax) derived from serum concentration of BNT327. Time Frame: from pre-dose to the end of study treatment (up to approximately 2 years)-
- Part 1 and Part 2: Number of participants developing detectable anti-BNT327 antibodies in serum. Time Frame: from pre-dose to the end of study treatment (up to approximately 2 years)
研究者
Clinical Trial Information Desk
Scientific
BioNTech SE