A Phase 1, Open-Label, Dose-Escalation Clinical Trial of Tumor Necrosis Factor Alpha and Interleukin 2 Coding Oncolytic Adenovirus TILT-123 in Melanoma Patients Receiving Adoptive Cell Therapy With Tumor Infiltrating Lymphocytes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 17
- 试验地点
- 2
- 主要终点
- Number of Participants with any (serious and non-serious) Adverse Events prior to TIL administration.
研究概览
简要总结
This is an open-label, phase 1, first-in-human (FIH), dose-escalation, multicenter, multinational trial evaluating the safety of oncolytic adenovirus TILT-123 as monotherapy and in association with T-cell therapy with TILs in metastatic melanoma patients.
详细描述
The primary objective of the trial is to evaluate the safety of TILT-123. The approach has the potential to a) increase the efficacy of adoptive T-cell therapy, b) remove the need for toxic pre- and post-conditioning regimens, c) yield the combined anti-tumor benefits of armed oncolytic viruses and T-cell therapy.
Dose escalation of TILT-123 injection will take place between cohorts not intra-patient and will be determined based on Dose Limiting Toxicities (DLTs).
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed and dated informed consent before any trial-related activities.
- •Male or female, between 18-75 years of age (both included).
- •Pathologically confirmed previously treated refractory or recurrent stage 3-4 melanoma, which cannot be treated with curative intent with available therapies.
- •At least one prior line of medical treatment is required (for example checkpoint inhibitors, kinase inhibitors, interleukin-2). Multiple prior therapies (e.g. surgery, checkpoint inhibitors, kinase inhibitors, interleukin-2, interferon, chemotherapy, radiation) are allowed.
- •A > 9 mm tumor (in diameter, typically a minimum of 1 cm3 in volume) without signs of necrosis must be available for biopsy/operation to enable growing of TILs.
- •At least one additional tumor (>14 mm in diameter) must be available for injections and biopsies for correlative analyses. The disease burden must be measurable, but does not need to fulfil RECIST 1.
- •Eligible for adoptive T-cell therapy with tumor infiltrating lymphocytes
- •Adequate hepatic, cardiac and renal functions as following:
- •Platelets > 75 000/mm3
- •Haemoglobin ≥ 100 g/L.
- •AST and ALT < 3 x ULN.
- •GFR >60 ml/min (Cockcroft-Gault formula).
- •Leukocytes (WBC) > 3,0
- •Bilirubin <1.5 x ULN
- •Men and women must be willing to use adequate forms of contraception from screening, during the trial, and for a minimum of 90 days after end of treatment, in accordance with the following:
- •Women of childbearing potential: Barrier contraceptive method (i.e. condom) must be used in addition to one of the following methods: Intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections).
- •Women not of childbearing potential: Barrier contraceptive method (i.e. condom) must be used.
- •Men: Barrier contraceptive method (i.e. condom) must be used.
- •Demonstrated WHO performance score of 0-1 at screening.
- •Life expectancy time longer than 3 months.
- •Capable of understanding and complying with parameters as outlined in the protocol.
- •BRAF negative or positive.
排除标准
- •Use of immunosuppressive medications (corticosteroids or drugs used in treatment of autoimmune disease). Exempted are the following which can be allowed at screening and during the trial: replacement corticosteroids if e.g. the patient has adrenal insufficiency after prior immunotherapy; pulmonal and topical treatments; up to 20 mg of prednisone/prednisolone.
- •History of another active invasive cancer as judged by the investigator within the past 3 years except basalioma.
- •Treated with any anti-cancer therapy for melanoma 30 days prior to enrolment. Anti-cancer therapy for melanoma is defined as anti-cancer agents (immunotherapy, signal-transduction inhibitors [e.g. BRAF and MEK inhibitors], cytotoxic chemotherapy), radiotherapy and investigational agents. An investigational agent is any drug or therapy that is currently not approved for use in humans.
- •Uncontrolled cardiac or vascular diseases.
- •History of heart attack or cerebral stroke within the previous 12 months before screening or is not recovered from an older heart attack or cerebral stroke.
- •LDH value > 3 x ULN.
- •History of hepatic dysfunction, hepatitis or HIV.
- •History of coagulation disorder.
- •Any other disease which prevent participation in the opinion of the investigator.
- •Female patients who are pregnant, breastfeeding or intends to become pregnant.
- •Untreated brain metastases. Treated brain metastases which have not progressed in 3 months prior to screening are allowed.
- •Previously treated with any oncolytic adenovirus that was administered intratumorally.
- •Previously treated with adoptive cell therapy.
- •Allergy to TILT-123, TIL, or ingredients present in the investigational medicinal products.
- •Administered an investigational medicinal product or device in another clinical trial within 30 days prior to screening
研究组 & 干预措施
TILT-123
Patients will receive administrations of TILT-123. Patients will also receive Tumor Infiltrating Lymphocytes (TILs) during the treatment phase.
Escalation to the next dose of TILT-123 level will occur when the safety data has been evaluated for all patients in the preceding dose level.
干预措施: TILT-123 (Biological)
结局指标
主要结局
Number of Participants with any (serious and non-serious) Adverse Events prior to TIL administration.
时间窗: 36 days
Number of Participants with abnormal laboratory values prior to TIL administration.
时间窗: 36 days
Number of Participants with vital sign abnormalities prior to TIL administration.
时间窗: 36 days
Safety assessed by 12- lead electrocardiograms (ECGs) Adverse Events prior to TIL administration.
时间窗: 36 days
Any clinically significant adverse changes on the ECG will be reported as Adverse Events.
次要结局
未报告次要终点