Dose-finding Phase 1 Trial: Evaluating Safety and Biomarkers Using DK210 (EGFR) for Inoperable Locally Advanced and/or Metastatic EGFR+ Tumors With Progressive Disease Failing Systemic Therapy
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 39
- 试验地点
- 7
- 主要终点
- Incidence of Adverse Events (AEs) with DK210 (EGFR)
研究概览
简要总结
This study will evaluate safety, pharmacodynamics and biomarkers of subcutaneous (SC) DK210(EGFR) given as monotherapy and in combination with immunotherapy, chemotherapy or radiation.
详细描述
This study will evaluate DK210(EGFR) as monotherapy and combination in subjects with advanced solid EGFR expressing cancers with documented progressive disease after at least one line of systemic treatment (staging performed by local standard).
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
- •ECOG performance status of 0-1
- •Life expectancy of >3 months according to the investigator's judgment
- •Solid tumors known for response on Il-2 or Il-10 and/or high expression of EGFR like all Non-small cell Lung, Skin, Head and Neck, Colon, Kidney, Bladder, Pancreatic cancers and all squamous cell carcinoma of other organs can be included with a classical histology report, specific EGFR expression or amplification reports are needed for other solid tumor types like gynecologic, prostate or triple negative breast cancer
- •Measurable disease, defined as at least one (non-irradiated) lesion measurable on CT/MRI or bone scan as defined by RECIST 1.
- •Progressive disease (PD) at study entry defined as one or more of the following criteria:
- •Clinical PD with performance decline, clinical symptoms and/or observed tumor growth
- •PD documented with imaging showing at least 20% growth (largest diameter) and/or new lesions
- •Adequate cardiovascular, hematological, liver, and renal function.
- •Subjects have failed one or more lines of systemic therapy and have not been operated on or receiving anti-cancer medication for at least 4 weeks.
- •Males and females of childbearing potential must agree to use effective contraception starting prior to the first day of treatment and continuing during treatment
- •Additional criteria may apply
排除标准
- •Subjects with documented diffuse peritoneal disease or persistent abundant ascites
- •Subjects with known prolonged QtC interval
- •Concomitant or recent (<4 weeks or 5 half-lives of the last treatment, whichever is shorter) treatment with agents with anti-tumor activity, including immunotherapies, or experimental therapies. Bone treatments and supportive care can be continued
- •Major surgery within 4 weeks, Radiation therapy for the treatment of metastases within less than 3 weeks (if single fraction of radiotherapy, then within 2 weeks) and radionuclide therapy for the treatment of metastases within 4 weeks prior to screening
- •Uncontrolled intercurrent illness including, but not limited to, ongoing and uncontrolled infection (TBC, COVID or HIV patients treated with at least two anti-retroviral drugs and control of their infection with at least 500 /mm3 CD4+ T-cells in their blood and patients cured from Hepatitis B or C (i.e negativity of PCR) and liver function compatible with eligibility criteria are allowed to participate), multiple myeloma, multiple sclerosis, myasthenia gravis, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirement
- •Any other conditions that, in the investigator's opinion, might indicate the subject to be unsuitable for the study
- •Additional criteria may apply
研究组 & 干预措施
DK210 (EGFR) Monotherapy (Dose escalation and expansion)
DK210 (EGFR) will be administered as monotherapy three times per week via subcutaneous (SC) administration. Dose will be escalated from 0.025 mg/kg to 0.3 mg/kg or until unacceptable toxicity, disease progression, or withdrawal of consent. An expansion cohort at the optimal dose will be enrolled in parallel with the combination arms.
干预措施: DK210 (EGFR) (Biological)
DK210 (EGFR) + chemotherapy
In patients with good tolerance of first line systemic therapy, DK210 (EGFR) will be administered three times per week via subcutaneous (SC) administration in combination with second-line intravenous (IV) chemotherapy until unacceptable toxicity, disease progression, or withdrawal of consent
干预措施: DK210 (EGFR) (Biological)
DK210 (EGFR) + chemotherapy
In patients with good tolerance of first line systemic therapy, DK210 (EGFR) will be administered three times per week via subcutaneous (SC) administration in combination with second-line intravenous (IV) chemotherapy until unacceptable toxicity, disease progression, or withdrawal of consent
干预措施: Chemotherapy (Drug)
DK210 (EGFR) + radiation
In patients with need of palliative radiation, DK210 (EGFR) will be administered three times per week via subcutaneous (SC) administration in combination with short course radiation therapy (10 fractions or less) until unacceptable toxicity, disease progression, or withdrawal of consent
干预措施: DK210 (EGFR) (Biological)
DK210 (EGFR) + radiation
In patients with need of palliative radiation, DK210 (EGFR) will be administered three times per week via subcutaneous (SC) administration in combination with short course radiation therapy (10 fractions or less) until unacceptable toxicity, disease progression, or withdrawal of consent
干预措施: Radiation therapy (Radiation)
DK210 (EGFR) + immunotherapy
In patients with good tolerance of first line immunotherapy, DK210 (EGFR) will be administered three times per week via subcutaneous (SC) administration in combination with intravenous (IV) immune checkpoint blockers until unacceptable toxicity, disease progression, or withdrawal of consent
干预措施: DK210 (EGFR) (Biological)
DK210 (EGFR) + immunotherapy
In patients with good tolerance of first line immunotherapy, DK210 (EGFR) will be administered three times per week via subcutaneous (SC) administration in combination with intravenous (IV) immune checkpoint blockers until unacceptable toxicity, disease progression, or withdrawal of consent
干预措施: Immune checkpoint blockers (Biological)
结局指标
主要结局
Incidence of Adverse Events (AEs) with DK210 (EGFR)
时间窗: Minimum of 90 days from initiation of experimental therapy
Based on toxicities observed
Identify recommended dose of DK210 (EGFR)
时间窗: Initiation of therapy up to day 90
Based on toxicities observed
Incidence of Adverse Events (AE) of DK210 (EGFR) in combination with radiation, chemotherapy, or checkpoint blockers in Parts B, C, D
时间窗: Minimum of 90 days from initiation of experimental therapy
Based on toxicities observed
次要结局
- Serum concentrations of DK210 (EGFR) will be determined at various time points(From initiation of treatment through 12 months (every 9 weeks))
- Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry at various time points(From initiation of treatment through day 63)
- Overall response rate (ORR)(Initiation of therapy up to approximately 12 months)
- Best response rate at 9 weeks(Initiation of therapy through Day 63)
- Progression-free (PFS)(Study Day 1 until the date of first documented progression or date of death from any cause, assessed up to approximately 24 months)
- Overall Survival (OS)(Assessed up to 24 months)
- Serum will be assayed for the presence of anti-DK210 (EGFR) antibodies(From initiation of treatment through 12 months (every 9 weeks))
- Serum concentrations of proinflammatory cytokines such as IL-6, IL-10, TNFa, IL-1b, and interferon (IFN)-g will be assessed at various time points(From initiation of treatment through 12 months (every 9 weeks))