A Study of HLX18 vs. OPDIVO® in Multiple Resected Solid Tumors

Официальное название

A Multicenter, Randomized, Double-Blind, Parallel-Controlled Phase I Clinical Study to Evaluate the Pharmacokinetic Profile, Efficacy, Safety and Immunogenicity of HLX18 vs. OPDIVO® (US-sourced OPDIVO®) in Multiple Resected Solid Tumors

Обзор

This is a multicenter, randomized, double-blind, parallel-controlled phase I clinical study to evaluate the similarity in PK profile, efficacy, safety and immunogenicity of HLX18 and OPDIVO® in patients with resected esophageal or gastroesophageal junction cancer (EC/GEJC), melanoma (MEL), or urothelial carcinoma (UC).

Вмешательства

• Препарат HLX18
  Participants will receive HLX18 (480 mg) on Day 1 of each 4-week cycle
• Препарат OPDIVO®
  Participants will receive OPDIVO® (480 mg) on Day 1 of each 4-week cycle

Первичные конечные точки

• AUC0-28d [Срок оценки: From time 0 to 28 days after the 1st dose(4 weeks)]
• AUCss [Срок оценки: From time 0 to 28 days after the 4th dose(16 weeks)]

Вторичные конечные точки (8)

• maximum serum drug concentration (Cmax) [Срок оценки: up to 16 weeks]
• trough serum drug concentration (Ctrough) [Срок оценки: up to 16 weeks]
• maximum serum drug concentration at steady state (Cmax,ss) [Срок оценки: up to 16 weeks]
• trough serum drug concentration at steady state (Ctrough,ss) [Срок оценки: up to 16 weeks]
• Disease-free survival (DFS) [Срок оценки: up to 12 months]
• Adverse events (AEs); Serious adverse events (SAEs); Adverse events of special interest (AESIs) (including immune-related adverse events and infusion-related reactions) [Срок оценки: From enrollment to the end of 90-day safety follow-up (up to 15 months)]
• Number of participants with abnormal vital signs, abnormal physical examination findings, abnormal Laboratory tests results (hematology, serum chemistry, thyroid function, coagulation function, and myocardial markers) or abnormal 12-lead ECG readings. [Срок оценки: From enrollment to the end of 30-day safety follow-up (up to 13 months)]
• Incidence of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) [Срок оценки: up to 24 weeks]

Критерии участия

Критерии включения

• Participants must have signed and dated an IRB/IEC approved written informed consent form.
• Aged 18 to 70 years at the time of signing the ICF.
• 18 kg/m² ≤ BMI ≤ 30 kg/m² and 50 kg ≤ body weight ≤ 85 kg.
• Histologically confirmed solid tumors (EC/GEJC, Melanoma, or UC) status post R0 resection.
• For EC/GEJC: residual pathologic disease (non-pCR) following neoadjuvant chemoradiotherapy and R0 resection.
• For Melanoma: Stage IIB-IV after complete surgical resection with documented negative margins.
• For UC: High-risk muscle-invasive urothelial carcinoma (MIUC) following radical resection (R0).
• Documented disease-free status (no recurrence) by imaging and physical exam within 4 weeks prior to randomization.
• Adequate recovery from prior surgery or systemic therapy.
• ECOG Performance Status of 0.
• Adequate organ function.
• Agreement to use effective contraception (negative pregnancy test for WOCBP).

Критерии исключения

• History of illicit drug use or alcohol abuse within 12 months prior to randomization.
• Tumor-specific exclusions: cervical esophageal cancer, Stage IV EC/GEJC, or ocular melanoma.
• UC-specific surgical exclusions: status post partial cystectomy or partial nephrectomy.
• EC/GEJC treatment violations: failure to receive mandatory preoperative concurrent CRT (mono-therapy is ineligible).
• Prior treatment with nivolumab or any other immune checkpoint inhibitors (PD-1, PD-L1, CTLA-4).
• Other primary active malignancies within 5 years or history of organ/bone marrow transplantation.
• Significant cardiovascular disease (MI, cerebrovascular disease) or unstable arrhythmia (QTc > 450ms/470ms) within 6 months.
• Chronic heart failure (NYHA Class III-IV) or LVEF < 50% at screening.
• Presence of interstitial pneumonia, pneumonitis, or severe lung function abnormalities.
• Active autoimmune disease requiring systemic immunosuppressive therapy.
• Known HIV infection, active Hepatitis B/C, or active pulmonary tuberculosis.
• Peripheral neuropathy ≥ Grade 2 or history of carcinomatosis meningitis.
• Use of systemic corticosteroids (>10 mg/day prednisone equivalent), immunosuppressants, or live vaccines within 28 days.
• Recent or planned participation in other investigational drug, device, or surgical studies.
• Severe allergic reactions to monoclonal antibodies or any condition deemed unsuitable by the investigator.
• The investigator has a clear reason to believe that participation in this study would be detrimental to the participant.

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

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 7 центров

• Fujian Medical University Union Hospital — Фучжоу
• The First Affiliated Hospital Zhejiang University School Of Medicine — Ханчжоу
• The First Affiliated Hospital of Henan University of Science & Technology — Luoyang
• The Second Hospital of Tianjin Medical University — Тяньцзинь
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou
• Union Hospital, Tongji Medical College,Huazhong University of Science and Technology — Ухань
• The Second Affiliated Hospital of Xi'an Jiaotong University — Сиань

Идентификаторы

NCT: NCT07518043 · HLX18-MRST001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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