A Study of SIM0689 in Adult Participants With Locally Advanced or Metastatic Solid Tumors

Официальное название

Phase I First-in-Human, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0689 in Adult Participants With Locally Advanced or Metastatic Solid Tumors

Обзор

This study will evaluate the safety, of SIM0689 and how the body processes it, how it affects the body, and its early signs of activity against tumors when given alone to Adult Participants with Locally Advanced or Metastatic Solid Tumors. The study has a dose escalation part to find the highest dose that can be given safely, or recommended dose (RD) for SIM0689 when given alone, and a dose expansion part in subjects with specific tumor types treated with SIM0689 as a single agent at RD.

Вмешательства

• Препарат SIM0689 for Injection
  SIM0689 for Injection is a Programmed Cell Death Protein 1(PD1) / Vascular Endothelial Growth Factor (VEGF) bispecific antibody.

Первичные конечные точки

• Dose-limiting toxicity (DLT) (Dose escalation) [Срок оценки: at the end of Cycle 1 (each cycle is 28 days)]
• Maximum tolerated dose (MTD)and / or Recommended dose (RD) (Dose escalation) [Срок оценки: Up to approximately 2 years]
• Objective Response Rate (ORR) (Dose expansion) [Срок оценки: Up to approximately 2 years]

Вторичные конечные точки (8)

• Adverse event rate [Срок оценки: up to approximately 2 years]
• Pharmacokinetics: The area under the curve (AUC) [Срок оценки: up to approximately 2 years]
• Pharmacokinetics: Peak concentration (Cmax) [Срок оценки: Up to approximately 2 years]
• Pharmacokinetics: T1/2 [Срок оценки: Up to approximately 2 years]
• Pharmacokinetics: Tmax [Срок оценки: Up to approximately 2 years]
• Immunogenicity [Срок оценки: Up to approximately 2 years]
• Immunogenicity [Срок оценки: Up to approximately 2 years]
• Immunogenicity [Срок оценки: Up to approximately 2 years]

Критерии участия

Критерии включения

• In dose-escalation cohorts (Part 1), histologically or cytologically documented advanced or metastatic solid tumor that is refractory/relapsed to standard therapies, or for which no effective standard therapy is available, or the subject refuses standard therapy.
• In the dose-expansion cohorts (Part 2), histologically or cytologically confirmed selected advanced solid tumors.
• Subjects must have at least one measurable lesion according to RECIST Version1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.
• Adequate organ function.
• Available archived tumor tissue sample to allow for correlative biomarker studies. If unavailable or unsuitable, the subject must consent and undergo fresh tumor biopsy.
• Life expectancy ≥12 weeks.
• Patients of childbearing potential (male and female) must agree to use reliable methods of contraception until at least 180 days after the last dose.

Критерии исключения

• Symptomatic brain metastases.
• Serious non-healing wounds, ulcers or fractures.
• Toxicity from previous treatment has to restore to ≤ grade 1.
• Major surgery (excluding biopsy) or significant trauma within 4 weeks prior to enrollment.
• Use of aspirin (> 325 mg/day) within 6 months prior to the first dose.
• Active hepatitis B or hepatitis C.
• Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
• Known hereditary or acquired predisposition to bleeding and thrombosis.
• History of gastrointestinal perforation, gastrointestinal bleeding, fistula, or any life-threatening bleeding event within 6 months prior to enrollment.
• Prior permanent discontinuation of PD-(L)1 and/or VEGF monoclonal antibody because of immune/anti-angiogenesis toxicities, or history of Grade ≥3 immune/anti-angiogenesis-related AEs
• Known or suspected active autoimmune disease.
• Patients with proteinuria at screening (Urine protein >2+ at screening, or 2+ urine protein accompanied by 24-h urine protein ≥1 g/24 h).
• History of myocardial infarction or stroke within 6 months prior to enrollment.
• Subjects with clinically significant cardiovascular disease within 6 months prior to the first dose.
• Pregnant and lactating women.
• Known allergies to any excipient in the study drug.

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
• The First Affiliated Hospital of Zhengzhou University — Чжэнчжоу
• Hunan Cancer Hospital — Чанша
• The First Hospital of China Medical University — Шэньян
• Cancer Hospital of Shandong First Medical University — Цзинань
• The First Affiliated Hospital, Zhejiang University school of Medicine — Ханчжоу

Идентификаторы

NCT: NCT07660432 · SIM0689-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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