SHR-A1904 Combinations in CLDN18.2-Positive Advanced Solid Tumor

Официальное название

A Phase Ib/III Study of SHR-A1904 Combinations in CLDN18.2-Positive Advanced Solid Tumor

Обзор

This study consists of two research phases: Phase Ib (includes dose escalation stage and efficacy expansion stage): To explore the safety, tolerability and initial efficacy of SHR-A1904 in the treatment of CLDN18.2-positive advanced solid tumors, and to determine the recommended dose and recommended population for the Phase III combination study. Phase III: A randomized, Open-Label, multicenter clinical study of SHR-A1904 combined with chemotherapy and immunotherapy Versus chemotherapy combined with immunotherapy for CLDN18.2-positive advanced solid tumors.

Вмешательства

• Препарат SHR-A1904; Adebrelimab
  SHR-A1904 combined with Adebrelimab: SHR-A1904+ Adebrelimab
• Препарат SHR-A1904; CAPOX; Adebrelimab
  SHR-A1904 combined with Adebrelimab and CAPOX (Capecitabine, Oxaliplatin)

Первичные конечные точки

• Incidence and severity of AE [Срок оценки: Up to follow-up period, approximately 24 months]
• Dose Limiting Toxicity (DLT) [Срок оценки: approximately 24 months]
• Maximal Tolerable Dose (MTD) [Срок оценки: approximately 24 months]
• Phase III Recommended Dose (RP3D) [Срок оценки: approximately 24 months]
• Progression-free survival (PFS) assessed by blind Independent Center Review (BICR) based on RECIST 1.1 criteria [Срок оценки: approximately 36 months]

Вторичные конечные точки (6)

• SHR-A1904 toxin binding antibody [Срок оценки: approximately 24 months]
• SHR-A1904 Total antibody [Срок оценки: approximately 24 months]
• Immunogenicity indicators of SHR-A1904: drug resistant antibody (ADA) and neutralizing antibody (NAb) [Срок оценки: approximately 24 months]
• Expression level of CLDN18.2 in tumor tissues [Срок оценки: approximately 24 months]
• Overall survival (OS) [Срок оценки: approximately 36 months]
• Incidence and severity of AE [Срок оценки: approximately 36 months]

Критерии участия

Критерии включения

• Age 18 to 75 years old (including boundary values);
• Volunteer to participate in this clinical study and sign informed consent;
• ECOG score 0-1;
• Expected survival ≥3 months;
• Pathologically confirmed locally advanced unresectable or metastatic solid tumors;
• positive CLDN18.2 expression in tumor tissue;
• There is at least one measurable lesion that meets the RECIST 1.1 criteria;
• Adequate bone marrow and organ function.

Критерии исключения

• Plan to receive any other antitumor therapy during this trial; Received other investigational drugs or treatments that are not on the market within 4 weeks prior to the first administration; Anti-tumor therapy, such as chemotherapy, radiotherapy, biotherapy, targeted therapy or immunotherapy, was received within 4 weeks before the first administration of the study drug. Palliative radiotherapy or local therapy within 2 weeks before the first administration of the study drug; Had major surgery other than diagnosis or biopsy within the 4 weeks prior to the first administration or randomization and required elective surgery during the trial.
• HER2 expression in tumor tissue is positive.
• The adverse reactions of previous anti-tumor therapy has not recovered to NCI-CTCAE v5.0 grade≤ 1.
• Has ≥ grade 2 peripheral sensory neuropathy.
• Has an allergic reaction to any of the components treated in this study, or are allergic to humanized monoclonal antibody products.
• Has a history or current history of meningeal metastasis; or active brain metastases.
• Presence of dysphagia or other factors affecting the use of oral medications.
• Additional malignancy within the five years prior to the first administration or randomization.
• Has an active autoimmune disease or a history of autoimmune disease.
• Received systemic use of corticosteroids or other immunosuppressants for immunosuppressive effects within 14 days prior to the first administration or randomization.
• Has a history of clinically significant lung disease.
• Has serosal effusion ≥ grade 3 (based on NCI CTCAE5.0 criteria).
• There was an active infection requiring systemic treatment within 2 weeks prior to the first administration or randomization.
• A history of immunodeficiency, including a positive HIV test; Presence of active hepatitis B or hepatitis C.
• People who have previously received allogeneic hematopoietic stem cell transplantation or organ transplantation.
• Has severe cardiovascular and cerebrovascular diseases.
• Gastrointestinal perforation and/or gastrointestinal fistula within the last 6 months prior to the first administration or randomization; Active gastrointestinal bleeding occurred 3 months before the first administration or randomization.
• In the investigator's judgment, the subject has other factors that could have affected the study results or led to the forced termination of the study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Sun Yat-sen University Cancer Center — Гуанчжоу

Идентификаторы

NCT: NCT06350006 · SHR-A1904-301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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