A Clinical Study on the Safety, Tolerability, Pharmacokinetics and Efficacy of SHR-1049 in Patients With Advanced Solid Tumors

Официальное название

An Open Label, Multicenter Phase I Clinical Study on the Safety, Tolerability, Pharmacokinetics and Efficacy of SHR-1049 Injection in Patients With Advanced Solid Tumors

Обзор

This study is a multicenter, open label, dose exploration/efficacy extension Phase I clinical trial aimed at evaluating the safety, tolerability, pharmacokinetics and efficacy of SHR-1049 injection in patients with advanced solid tumors.

Вмешательства

• Препарат SHR-1049 Injection
  SHR-1049 injection.

Первичные конечные точки

• The incidence and severity of dose-limiting toxicity (DLT). [Срок оценки: Expected results within one year.]
• Adverse events (AEs). [Срок оценки: Approximately 12 months after the last patient enrolled.]
• Serious adverse events (SAEs). [Срок оценки: Approximately 12 months after the last patient enrolled.]
• Maximum tolerated dose (MTD). [Срок оценки: Plan to obtain results within 10 months of the first dose ramp up.]
• Recommended dose for phase II clinical study (RP2D). [Срок оценки: Plan to obtain results within 20 months of the first dose ramp up.]

Вторичные конечные точки (7)

• Pharmacokinetics (PK) indicator - Blood drug concentration. [Срок оценки: The plan is to complete all evaluations within 2 years.]
• Immunogenic indicator - Anti-drug antibody (ADA) levels. [Срок оценки: The plan is to complete all evaluations within 2 years.]
• Effectiveness indicator - Researchers evaluated objective response rate (ORR). [Срок оценки: Approximately 12 months after the last patient enrolled.]
• Effectiveness indicator - Researchers evaluated duration of response (DoR). [Срок оценки: Approximately 12 months after the last patient enrolled.]
• Effectiveness indicator - Researchers evaluated disease control rate (DCR). [Срок оценки: Approximately 12 months after the last patient enrolled.]
• Effectiveness indicator - Researchers evaluated progression free survival (PFS). [Срок оценки: Approximately 12 months after the last patient enrolled.]
• Effectiveness indicator - Researchers evaluated overall survival (OS) based on the RECIST v1.1 evaluation criteria for solid tumor treatment efficacy. [Срок оценки: Approximately 12 months after the last patient enrolled.]

Критерии участия

Критерии включения

• Voluntarily join this study, sign the informed consent form, have good compliance, and can cooperate with follow-up;
• Age range of 18-75 years old (including 18 and 75 years old, calculated on the day of signing informed consent), both male and female are eligible;
• Dose exploration stage: Participants with advanced or metastatic solid tumors diagnosed by tissue or cytological pathology who have failed standard treatment (disease progression or toxicity intolerance) or have no effective standard treatment;
• Stage of efficacy extension: Late stage or metastatic solid tumors diagnosed by tissue or cytological pathology;
• Able to provide sufficient fresh or archived tumor tissue specimens for third-party central laboratories designated by the sponsor to test expression levels; For participants who are unable to provide tumor tissue samples, the decision to enroll will be made after joint evaluation by the researchers and the sponsor;
• At least one measurable lesion that meets RECIST v1.1 criteria; Lesions that have undergone local treatment, if there is clear evidence of significant progression after treatment, can be selected as target lesions;
• ECOG PS score: 0 to 1;
• Expected survival period ≥ 12 weeks;
• The function of important organs meets the requirements;
• Female participants with fertility must have a negative serum HCG test within 7 days prior to their first medication and must be non lactating; Female participants with fertility must agree to use contraception and avoid egg donation for a period of 7 months from the signing of the informed consent form until the last administration of the investigational drug; Male participants whose partners are fertile women must agree to contraception and avoid donating sperm for a period of 4 months from the signing of the informed consent form until the last administration of the investigational drug.

Критерии исключения

• Accompanied by untreated or active central nervous system (CNS) tumor metastasis; Participants with a history of meningeal metastasis or current meningeal metastasis;
• Imaging shows tumor invasion of large blood vessels or unclear boundary with blood vessels; Or it may be determined by researchers that the participant's tumor has a high possibility of invading important blood vessels and causing fatal massive bleeding during treatment;
• Previous or concurrent presence of other malignant tumors;
• Chest effusion, pericardial effusion, or abdominal effusion that is accompanied by clinical symptoms, difficult to control, or moderate or above; If fluid drainage is performed (excluding diagnostic puncture surgery), those who have been stable for at least 2 weeks after drainage can be included in the group;
• Interstitial pneumonia/interstitial lung disease, non infectious pneumonia (such as radiation pneumonitis) that previously required steroid treatment; Currently present or suspected of having interstitial pneumonia/interstitial lung disease, non infectious pneumonia, or other active pneumonia; Severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, and other lung damage occurred within 6 months prior to the first use of medication; Individuals with active pulmonary tuberculosis;
• Accompanied by poorly controlled or severe cardiovascular disease;
• Within one month prior to the first medication, there has been a bleeding event with NCI-CTCAE v5.0 grade ≥ 2;
• Those who have experienced or are expected to experience gastrointestinal perforation or fistula, tracheal fistula, urethral fistula, or abdominal abscess within 3 months before the first medication;
• Symptoms and signs of gastrointestinal obstruction or gastrointestinal obstruction within 3 months prior to the first use of medication;
• Participants who have experienced a severe infection within one month prior to their first medication;
• History of immunodeficiency, including HIV test positive, other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; Participants known to have active hepatitis or active hepatitis C;
• Patients who have previously undergone surgery (excluding diagnostic surgery), radiotherapy, local treatment, chemotherapy, macromolecular targeted therapy, anti-tumor immunotherapy, and have completed treatment (last medication) less than 4 weeks after the first medication; Small molecule targeted drugs (including other oral targeted drugs used in clinical trials) with less than 5 half lives or 4 weeks (whichever is shorter) between the last dose and the first dose;
• Previously received drug treatment with the same mechanism as the experimental drug;
• According to NCI-CTCAE v5.0 classification, those whose toxicity caused by previous anti-tumor therapy has not yet recovered to ≤ grade 1;
• Individuals known to be allergic to any component or other antibody drugs of SHR-1049 product;
• Those who have received attenuated live vaccine within 4 weeks before the first administration or are likely to receive attenuated live vaccine during treatment and within 60 days after the last administration;
• According to the researcher's judgment, there are other factors that may affect the research results or force the termination of this study midway.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of College of Medicine, Zhejiang University — Ханчжоу

Идентификаторы

NCT: NCT07380334 · SHR-1049-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗