A Clinical Study of SHR-9839 as Monotherapy or in Combination With Chemotherapy Plus Adebrelimab Versus Chemotherapy Plus Adebrelimab in Patients With Advanced Esophageal Squamous Cell Carcinoma

Официальное название

A Randomized, Controlled, Open-label, Multicenter Phase II Clinical Study of SHR-9839 as Monotherapy or in Combination With Chemotherapy Plus Adebrelimab Versus Chemotherapy Plus Adebrelimab in Patients With Advanced Esophageal Squamous Cell Carcinoma

Обзор

An open-label, multicenter, randomized, phase II clinical trial to evaluate the safety, tolerability and efficacy of SHR-9839(sc) as monotherapy or in combination with chemotherapy plus adebelimab in patients with advanced esophageal squamous cell carcinoma (ESCC).

Вмешательства

• Препарат SHR-9839(sc) for Injection
  SHR-9839(sc) for Injection，dose level 1
• Препарат SHR-9839(sc) for Injection、Adebrelimab Injection、Paclitaxel for Injection、Cisplatin Injecion
  Safety run-in Stage: SHR-9839(sc) for Injection ,dose level 1 or lower dose、Adebrelimab Injection、Paclitaxel for Injection、Cisplatin Injecion; Dose extension Stage: SHR-9839(sc) for Injection,dose according to Safety run-in Stage、Adebrelimab Injection、Paclitaxel for Injection、Cisplatin Injecion or Adebrelimab Injection、Paclitaxel for Injection、Cisplatin Injecion

Первичные конечные точки

• ORR：Objective Response Rate [Срок оценки: First administration to end of treatment visit about 1year]

Вторичные конечные точки (8)

• DOR：Duration of relief [Срок оценки: First administration to disease progression about 1 year]
• DCR：Disease Control Rate [Срок оценки: First administration to disease progression about 1 year]
• PFS：progression-free survival [Срок оценки: First administration to disease progression about 1 year]
• OS：Overall Survival [Срок оценки: First administration until participant's death about 2 years]
• DLT：The Dose-Limiting Toxicity [Срок оценки: Post-dose at day 1 to Day21]
• MTD： The Maximum Tolerated Dose [Срок оценки: Post-dose at day 1 to Day21]
• AE：Incidence and severity of adverse events [Срок оценки: Sign the informed consent form until Safety follow-up completed about 1 year]
• ADA ：Anti-Drug Antibody [Срок оценки: Day1 pre-dose to 30 days after the last dose about 1 year]

Критерии участия

Критерии включения

• Capable of providing informed consent; has signed and dated the IRB/EC-approved informed consent form, and is willing and able to comply with scheduled study visits, examinations and all other protocol-specified procedures.
• Aged between 18 and 75 years inclusive at the time of informed consent signature, irrespective of gender.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histopathologically confirmed locally advanced unresectable or metastatic esophageal squamous cell carcinoma (ESCC).
• Expected survival ≥12 weeks.
• Must provide a minimum of 11 formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks or unstained tumor slides.
• Females of childbearing potential must agree to use adequate effective contraception from the date of informed consent, throughout study treatment, and for 9 months after the last dose of investigational product, and refrain from oocyte donation during this period (refer to subsequent section for detailed contraceptive requirements).

Критерии исключения

• Uncontrolled or symptomatic active central nervous system (CNS) metastases without adequate prior treatment.
• History of another concurrent malignant tumor diagnosed within 3 years prior to the first study drug administration.
• Presence of uncontrolled tumor-related pain as assessed by the Investigator.
• Severe cardiovascular or cerebrovascular diseases.
• History of interstitial lung disease (ILD) including idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans organizing pneumonia), drug-induced pneumonitis, radiation pneumonitis requiring steroid therapy; or suspected/unruled-out ILD on screening imaging; or moderate-to-severe pulmonary disease severely impairing respiratory function.
• Severe infection within 4 weeks before study treatment initiation, including but not limited to bacteremia, severe pneumonia or other infectious complications requiring hospitalization; active CTCAE Grade ≥2 infection requiring systemic antibiotics within 2 weeks prior to first dose (subjects on prophylactic antibiotics e.g., for urinary tract infection prophylaxis are eligible).
• History of immunodeficiency including positive HIV serology; active hepatitis B (positive HBsAg at screening plus HBV-DNA ≥2500 copies/mL /500 IU/mL or above local laboratory cutoff); or active hepatitis C (positive anti-HCV plus detectable HCV RNA).
• Active pulmonary tuberculosis within 1 year before enrollment by medical history or imaging; or prior active pulmonary tuberculosis >1 year ago without standardized anti-tuberculosis treatment.
• Toxicities/complications from prior anti-tumor therapies not recovered to NCI-CTCAE Grade ≤1 or levels specified by eligibility criteria; subjects with Grade ≤2 toxicities may enroll if deemed without safety risk by the Investigator.
• Receipt of any systemic anti-cancer therapy within 4 weeks prior to study treatment start.
• Thoracic radiotherapy >30 Gy within 24 weeks, non-thoracic radiotherapy >30 Gy within 4 weeks before first dose; palliative radiotherapy ≤30 Gy within 14 days before first dose (exception: subjects completing brain metastasis radiotherapy ≥14 days prior to first dose are permitted). For prior radioisotope therapy, a washout of at least five half-lives of the radioisotope is required before study enrollment.
• Major organ surgery (excluding core needle biopsy) or significant trauma within 4 weeks before first study drug, or planned elective surgery during trial participation; invasive minor surgery (biopsy, endoscopy, drainage procedure) within 7 days prior to first dose.
• Any other condition judged by the Investigator likely to interfere with trial conduct or subject safety, such as alcohol/drug abuse, uncontrolled severe illness (including psychiatric disorders) requiring concomitant medication, clinically significant abnormal laboratory findings, familial/social issues or other factors compromising subject safety or data integrity.

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 · 2 центра

• Beijing Cancer Hospital — Пекин
• The First Affiliated Hospital Of Zhengzhou University — Чжэнчжоу

Идентификаторы

NCT: NCT07751341 · SHR-9839-206

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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