Phase I, Open-labeled, Dose-escalation, Dose-expansion Study Evaluating the Safety, Tolerance, Pharmacokinetics, and Activity of IUAb190708 in Patients With Advanced or Recurrent Solid Tumors

Обзор

This study is to evaluate a novel cytotoxic anti-PD-L1, IUAb190708, for the treatment of tumor

Подробное описание

PD-L1 is universally expressed in various types of tumors and an important immune down-regulation factor in tumor microenvironment. Application of PD-L1 to cancer therapy is based on the inhibitory mechanism of the PD-L1/PD-1 pathway on T cell function, and as a result, PD-L1 blocking antibodies are developed, IUAb190708 is a humanized monoclonal immunoglobulin G1 κ subclass (IgG1) antibody that specifically recognizes PD-L1 (also known as CD274). Different from known PD-L1 blocking antibodies, i.e., they block the interaction of PD-L1 with PD-1 that recovers T cell function leading to indirect killing of tumor. Whereas IUAb190708 is to induce antibody dependent cell-mediated cytotoxicity (ADCC), i.e., it activates NK cells leading to direct killing of tumor.

IUAB190708 can be used as a monotherapy or in combination with other immunotherapies, chemotherapy, and radiation to improve the efficacy of tumor treatment.

In the open-label Phase I study, safety, tolerance, pharmacokinetics and activity of IUAb190708 in subjects with advanced or recurrent solid tumors will be evaluated, and MTD, DLT, and RP2D of IUAb190708 will be determined, and eligible subjects will be administered with IUAb190708 at different doses via intravenous infusion.

Вмешательства

• Препарат IUAb190708, a cytotoxic antibody
  a novel cytotoxic anti-PD-L1 antibody

Первичные конечные точки

• ORR [Срок оценки: 2 years]

Вторичные конечные точки (4)

• DOR [Срок оценки: 2 years]
• PFS [Срок оценки: 2 years]
• OS [Срок оценки: 2 years]
• Incidence and severity of adverse events (AEs) [Срок оценки: 2 years]

Критерии участия

Критерии включения

• Male or female adult, age 18 - 75, understanding and voluntarily signing an informed consent form
• A histologically confirmed diagnosis of Metastatic or locally advanced solid tumors, ineffective management of therapeutic regimen or currently no approved treatment available for the tumor, or unsuitable or refusing to receive standard treatment
• In Phase Ia, for tumors with approved indications of anti PD-1/PD-L1 treatment, unrestricted to PD-L1 expression; for tumors that have not yet been approved for indications, positive expression of PD-L1 required. In Phase Ib, positive expression of PD-L1 is required
• Subjects should provide fresh or archived tissue samples
• Subjects must have at least one measurable lesion per iRECIST
• Life expectancy ≥ 3 months
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
• Adequate organ function, and no blood transfusion, erythropoietin (EPO), and granulocyte colony-stimulating factor at least 14 days before the study drug administration
• All the female of child-bearing age must have a negative pregnancy test (unine or serum) during screening period and agree to use effective medical contraception from written informed consent to at least 6 months after the last administration of the study drug. Male partners also must agree to use effective medical contraception from written informed consent to at least 6 months after the last administration of the study drug.

Критерии исключения

• Serious/active infection or infection requiring intravenous antibiotic treatment within 4 weeks prior to the first dose of the study drug
• Receiving nitrosourea and mitomycin C within 6 weeks prior to the first dose of the study drug; receiving oral fluorouracil derivatives or small molecule targeted drugs within 2 weeks prior to the first dose or 5 half-lives of the drug (whichever is longer); receiving endocrine therapy, Immunotherapy, or Traditional Chinese Medicine for anti-tumor indications within 2 weeks prior to the first dose of the study drug; receiving other anti-tumor therapies, such as chemotherapy, radiation, biotherapy, besides as described above treatments, within 4 weeks prior to the first dose of the study drug
• Having other primary active malignant tumors within 5 years prior to the first dose of the study drug
• Having clinically significant cardiovascular diseases,
• Primary tumors of central nervous system or CNS metastatic tumors that have failed local treatment. For asymptomatic or clinically stable symptoms without the need for steroid hormones and other treatments for CNS metastasis lasting ≥ 28 days, CNS tumors under stable condition, including new CNS metastasis without any syndrome, confirmed by imaging during screening period can be enrolled.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
• History of allogeneic organ transplant.
• Known history of infection with Human Immunodeficiency Virus (HIV) or other acquired or congenital immunodeficiency.
• Patients with serious psychiatric or medical condition that could interfere with medication adherence.
• Receiving systemic corticosteroid therapy (prednisone >10 mg/day or Bioequivalent dose of hydrocortisone) within 2 week prior to the first dose of trial treatment or receiving any other form of systemic immunosuppressive medication, except the condition as described below: treatment with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids, or short-term (≤7 days) use of glucocorticoids for prophylactic treatment.
• Active or history of autoimmune disease that requires systemic treatment within 2 years prior to enrollment (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). But the subjects with the following diseases are allowed to be enrolled: Type I diabetes with stable condition after using fixed dose insulin; Autoimmune hypothyroidism that only requires hormone replacement therapy.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (such as bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia, interstitial pneumonia or evidence of active pneumonia detected during chest CT scan screening.
• Having experienced immune related adverse events of ≥ 3 grade during receiving any immunotherapy medication in the past.
• Adverse reactions from previous anti-tumor treatments have not yet recovered to ≤1 grade per CTCAE 5.0 (except alopecia and other adverse reactions that the investigator determines that there is no safety risk)
• Underwent major surgery within 4 weeks prior to the first dose of the study drug, or not fully recovered after surgery, or planned surgery within the expected participation time of the subject in the study or within 4 weeks after the last dose of the study drug.
• Treponema pallidum antibody positive; active hepatitis B (HBsAg positive with HBV-DNA>500IU/mL); active hepatitis C (except subjects with HCV antibody positive and HCV-RNA <lower limit of clinical research organization).
• Subjects with history or current evidence of any clinical condition or laboratory abnormality or other reasons are not suitable to participate in this clinical study by the investigator.
• Female who are pregnant or breastfeeding
• Subjects with history of other serious systemic diseases are not suitable to participate in this clinical study by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 6 центров

• Fujian Cancer Hospital — Фучжоу
• Anyang tumor hospital — Anyang
• Cancer hospital of Shandong First Medical University — Цзинань
• Fudan University Shanghai cancer center — Шанхай
• Shanghai Pulmonary hospital — Шанхай
• Shanghai Xinhua hospital — Шанхай

Идентификаторы

NCT: NCT07584954 · IUAb220910-01 · CTR20241263

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)
• NMPA/CDE CTR20241263 (платформа chinadrugtrials.org.cn)

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