A Phase I/Ib, Open-label, Multi-center, Study of QEQ278 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 16
- 主要终点
- Incidence and nature of Dose Limiting Toxicities (DLTs) during the DLT evaluation period for single agent QEQ278
研究概览
简要总结
To characterize safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of QEQ278 in adult patients with advanced/metastatic non-small cell lung cancer, esophageal squamous cell carcinoma, renal cell carcinoma, and human papilloma virus associated head and neck squamous cell carcinoma.
详细描述
This study is an open-label, phase I/Ib, multi-center study of QEQ278 as a single agent, consisting of a dose escalation part followed by a dose expansion part.
In the dose escalation part of the study, patients with non-small cell lung cancer (NSCLC), esophageal squamous cell carcinoma (ESCC), renal cell carcinoma (RCC), or human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) will be treated with QEQ278 single agent until the maximum tolerated dose (MTD) is reached or a lower recommended dose (RD) is established.
The study may enter the dose expansion, after an MTD(s) and/or RD(s) is declared in the dose escalation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent must be obtained prior to participation in the study.
- •Adult men and women ≥ 18 years of age.
- •Histologically confirmed and documented advanced malignancies (locally advanced malignancies, non-curable by surgery or radiotherapy and metastatic disease). Disease must be measurable, including presence of at least one measurable lesion, as determined by RECIST v1.
- •In the opinion of the treating investigator, patients must have received, but are not benefitting from standard therapies, be intolerant or ineligible to receive such therapy, or have no standard therapy option for the respective disease types (diseases listed below), as well as any other therapies deemed to be standard by local/institutional standard.
- •Non-small cell lung cancer
- •Esophageal squamous cell carcinoma
- •Renal cell carcinoma
- •HPV-associated head and neck squamous cell carcinoma
- •Must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. The patient must be willing to undergo a new tumor biopsy at screening and during treatment.
排除标准
- •Active previously documented or suspected autoimmune disease. Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur should not be excluded. Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
- •Patients with a history of or current interstitial lung disease or pneumonitis ≥ Grade
- •Patients who discontinued prior anti-PD-1 therapy due to an anti-PD-1-related toxicity
- •Clinically significant cardiac disease or risk factors at screening
- •Insufficient bone marrow function at screening:
- •Infections:
- •Known history of testing positive for Human Immunodeficiency Virus infection.
- •Active Hepatitis B and / or Hepatitis C.
- •Active, documented COVID-19 infection
- •Known history of tuberculosis
- •Any serious uncontrolled infection (acute or chronic).
- •Systemic chronic steroid therapy (>10 mg/day prednisone or equivalent) or any immunosuppressive therapy, other than replacement-dose steroids in the setting of adrenal insufficiency, within 7 days of the first dose of study treatment. Topical, inhaled, and ophthalmic steroids are allowed.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Part 1: Dose escalation
Dose escalation with QEQ278 single agent
干预措施: QEQ278 (Biological)
Part 2: Dose expansion
Dose expansion with QEQ278 single agent
干预措施: QEQ278 (Biological)
结局指标
主要结局
Incidence and nature of Dose Limiting Toxicities (DLTs) during the DLT evaluation period for single agent QEQ278
时间窗: 28 days
A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the DLT evaluation period and meets the criteria defined in the study protocol.
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
时间窗: Up to 31 months
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory values, vital signs, and electrocardiograms (ECGs) qualifying and reported as AEs.
Frequency of dose interruptions, reductions
时间窗: Up to 30 months
Number of dose interruptions of QEQ278 and number of dose reductions of QEQ278
Dose intensity
时间窗: Up to 30 months
Dose intensity of QEQ278 is defined as the ratio of actual cumulative dose received and actual duration of exposure.
次要结局
- Overall response rate (ORR) per RECIST v1.1(Up to 30 months)
- Progression-free survival (PFS) per RECIST v 1.1(Up to 30 months)
- Total body clearance (CL) of QEQ278(During first 168 days of treatment)
- Elimination half-life (T1/2) of QEQ278(During first 168 days of treatment)
- Duration of Response (DOR) per RECIST v1.1(Up to 30 months)
- Time to reach peak serum concentration (Tmax) of QEQ278(During first 168 days of treatment)
- Peak serum concentration (Cmax) of QEQ278(During first 168 days of treatment)
- Area under the concentration time curve (AUC) infinity of QEQ278(During first 168 days of treatment)
- Volume of distribution (Vz) of QEQ278(During first 168 days of treatment)
- Incidence of anti-drug antibody (ADA)(Day 1 and 15)
- Disease control rate (DCR) per RECIST v1.1(Up to 30 months)
- Area under the concentration time curve (AUC) last of QEQ278(During first 168 days of treatment)