A Phase 1, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of the PTK7-Targeted Antibody-drug Conjugate DAY301 in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 23
- 主要终点
- Phase 1a: Dose Escalation: Number of participants with reported Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This is a Phase 1a/1b, open-label, dose escalation and expansion study to evaluate the safety and anti-tumor activity of DAY301, a PTK7-directed antibody-drug conjugate (ADC) in participants with advanced or metastatic solid tumors. The study comprises of 2 phases: Phase 1a dose escalation where participants will be administered DAY301 at escalating dose levels to assess safety and tolerability, and to determine the maximum tolerated dose (MTD) and/or the recommended dose (RD); In Phase 1b dose expansion, DAY301 will be evaluated in dose expansion cohorts.
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
- •Histologically or cytologically confirmed diagnosis of advanced or metastatic solid tumors of the following histologies:
- •Ovarian cancer
- •Esophageal squamous cell carcinoma
- •Triple-negative breast cancer
- •Non-small cell lung cancer
- •Small cell lung cancer
- •Head and neck squamous cell carcinoma
- •Cervical squamous cell carcinoma
- •Endometrial cancers
- •(Participants must have been previously treated with standard of care systemic therapy, have refused standard therapy, or have no standard therapy available).
- •Availability of tumor tissue sample (either an archival specimen or a fresh biopsy) at screening
- •Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate organ function.
排除标准
- •Prior use of PTK7 targeting treatment (Phase 1a) or prior use of PTK7 targeting treatments and/or topoisomerase 1 (TOP1) inhibitors (Phase 1b).
- •Phase 1b disease-specific exclusion criteria:
- •Cohort 1: Neuroendocrine tumors or endometrial sarcoma (eg, stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas)
- •Cohort 2: Nasopharyngeal primary tumors.
- •Cohort 3: Ovarian cancer that progressed >6 months after the last dose of platinum-based chemotherapy (platinum-sensitive disease), or disease that did not respond (PR or complete response [CR]) to or progressed ≤91 days after the last dose of first-line platinum-based chemotherapy (primary platinum-refractory disease) .- History of small bowel obstruction requiring hospitalization within 3 months prior to the first dose of study treatment.
- •Ascites requiring frequent paracentesis (more often than approximately every 4 weeks) for symptomatic management, or new onset within 4 weeks prior to the first dose of study treatment. Patients with an indwelling catheter may be considered eligible, after consultation with the medical monitor.
- •Active or progressing brain metastases or evidence of leptomeningeal disease.
- •Persistent toxicities from previous systemic antineoplastic treatments of Grade >1, excluding alopecia and vitiligo.
- •Systemic antineoplastic therapy within five half-lives or 4 weeks, whichever is shorter, prior to first dose of study treatment, including investigational agents.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
DAY301 intravenous (IV) infusion
DAY301 will be administered at different dose levels in dose escalation and at the RD in dose expansion cohorts.
干预措施: DAY301 (Drug)
结局指标
主要结局
Phase 1a: Dose Escalation: Number of participants with reported Dose Limiting Toxicities (DLTs)
时间窗: Within 21 days of first infusion (Day 1)
To evaluate adverse events (AEs) considered dose limiting toxicities that occur in the first cycle of treatment (within a DLT observation period).
Phase 1a: Dose Escalation: Number of participants with reported adverse events (AEs) or serious AEs (SAEs)
时间窗: through the duration of treatment, up to approximately 12 months
The type, incidence, and severity of AEs and SAEs will be determined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Phase 1a: Dose Escalation: Frequency of dose interruptions
时间窗: through the duration of treatment, up to approximately 12 months
The frequency at which dose interruptions occur during dose-escalation
Phase 1a: Dose Escalation: Duration of dose interruptions
时间窗: through the duration of treatment, up to approximately 12 months
The duration of dose interruptions that occur during dose-escalation.
Phase 1a: Dose Escalation: Frequency of dose reductions
时间窗: through the duration of treatment, up to approximately 12 months
The frequency at which dose reductions occur during dose-escalation.
Phase 1a: Dose Escalation: Duration of dose reductions
时间窗: through the duration of treatment, up to approximately 12 months
The duration of dose reductions that occur during dose-escalation.
Phase 1b: Dose Expansion: Objective response rate
时间窗: through the duration of treatment, up to approximately 12 months-up
Objective response rate based on best overall response (BOR) will be assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Phase 1b: Dose Expansion: Number of participants reporting AEs and SAEs
时间窗: through the duration of treatment, up to approximately 12 months
The type, incidence, and severity of AEs and SAEs will be determined using the NCI CTCAE v5.0.
Phase 1b: Dose Expansion: Frequency of dose interruptions
时间窗: through the duration of treatment, up to approximately 12 months
The frequency at which dose interruptions occur during dose-expansion.
Phase 1b: Dose Expansion: Duration of dose interruption
时间窗: through the duration of treatment, up to approximately 12 months
The duration of dose interruptions that occur during dose-expansion.
Phase 1b: Dose Expansion: Frequency of dose reductions
时间窗: through the duration of treatment, up to approximately 12 months
The frequency at which dose reductions occur during dose-expansion.
Phase 1b: Dose Expansion: Duration of dose reductions
时间窗: through the duration of treatment, up to approximately 12 months
The duration of dose reductions that occur during dose-expansion.
Phase 1a: Dose Escalation: Number of participants with reported adverse events (AEs) and serious AEs (SAEs)
时间窗: through the duration of treatment, up to approximately 12 months
The type, incidence, and severity of AEs and SAEs will be determined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Phase 1b: Dose Expansion: Objective response rate
时间窗: through the duration of treatment, up to approximately 12 months
Objective response rate based on best overall response (BOR) will be assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
次要结局
- Phase 1a and Phase 1b: Maximum concentration (Cmax) of DAY301(Varying timepoints through the duration of treatment, up to approximately 12 months)
- Phase 1a and Phase 1b: time to Cmax (Tmax) of DAY301(Varying timepoints through the duration of treatment, up to approximately 12 months)
- Phase 1a and Phase 1b: area under the curve (AUC) of DAY301(Varying timepoints through the duration of treatment, up to approximately 12 months)
- Phase 1a and Phase 1b: terminal half-life (t1/2) of DAY301(Varying timepoints through the duration of treatment, up to approximately 12 months)
- Phase 1a Dose Escalation: Objective response rate(through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: Clinical Benefit rate (CBR)(through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: duration of response (DOR)(through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: time to response (TTR)(through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: Progression-free survival(through the duration of treatment, up to approximately 12 months)
- Phase 1b: Overall survival(through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: Number of participants with positive antidrug antibodies (ADAs)(varying timepoints through the duration of treatment, up to approximately 12 months)
- Phase 1a and Phase 1b: Maximum concentration (Cmax) of DAY301(Varying timepoints through the duration of treatment, up to approximately 12 months)
- Phase 1a and Phase 1b: time to Cmax (Tmax) of DAY301(Varying timepoints through the duration of treatment, up to approximately 12 months)
- Phase 1a and Phase 1b: area under the curve (AUC) of DAY301(Varying timepoints through the duration of treatment, up to approximately 12 months)
- Phase 1a and Phase 1b: terminal half-life (t1/2) of DAY301(Varying timepoints through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: Clinical Benefit rate (CBR)(through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: duration of response (DOR)(through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: time to response (TTR)(through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: Progression-free survival(through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: Number of participants with positive antidrug antibodies (ADAs)(varying timepoints through the duration of treatment, up to approximately 12 months)