Study of JAB-23E73 in Combination With Chemotherapy in Participants With Metastatic PDAC Harboring KRAS Gene Alterations

Официальное название

A Multicenter, Phase Ib/III Study to Evaluate JAB-23E73 in Combination With Nab-Paclitaxel and Gemcitabine in Participants With Metastatic Pancreatic Ductal Adenocarcinoma Harboring KRAS Gene Alterations

Обзор

The purpose of this study is to determine the safety and efficacy of pan KRAS inhibitor JAB-23E73 in combination with nab-paclitaxel and gemcitabine in participants with metastatic PDAC harboring KRAS gene alterations.

Подробное описание

This is a phase Ib/III, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antineoplastic activity of pan-KRAS inhibitor JAB-23E73 in combination with nab-paclitaxel and gemcitabine in treatment-naive participants with metastatic PDAC.

Phase Ib study：an open-label study, including dose escalation and backfill cohorts, with approximately 40-80 participants planned to be enrolled (including approximately 20-50 participants in the backfill cohort),Aiming to determine the recommended phase III dose \[RP3D\] within investigated patient population groups.

Phase III: Following confirmation of the efficacy and safety of JAB-23E73 in combination with the AG regimen in Phase Ib, a Phase III trial will be initiated to evaluate the efficacy and safety of JAB-23E73 plus AG versus AG alone for the treatment of metastatic PDAC.

Вмешательства

• Препарат JAB-23E73 tablet，nab-paclitaxel，gemcitabine
  Orally, intravenous (IV) infusion

Первичные конечные точки

• Dose limiting toxicities (DLT) [Срок оценки: Up to 28 days]
• Adverse events.safety evaluation [Срок оценки: Up to approximately 3 years]

Вторичные конечные точки (9)

• ORR [Срок оценки: Up to approximately 3 years]
• DOR [Срок оценки: Up to approximately 3 years]
• TTR [Срок оценки: Up to approximately 3 years]
• PFS [Срок оценки: Up to approximately 3 years]
• DCR [Срок оценки: Up to approximately 3 years]
• OS [Срок оценки: Up to approximately 3 years]
• PK [Срок оценки: Up to approximately 3 years]
• PK [Срок оценки: Up to approximately 3 years]
• PK [Срок оценки: Up to approximately 3 years]

Критерии участия

Критерии включения

1.Written informed consent signed by the participant or the participant's legally authorized representative must be obtained prior to performing any study-related procedures. 2. Histologically or cytologically confirmed metastatic PDAC.

3\. No prior systemic antitumor therapy for advanced disease (treatment-naïve). 4. Presence of KRAS gene alterations: be enrolled upon approval by the sponsor).

5\. ECOG performance status score of 0 or 1. 6. Adequate organ function.

Критерии исключения

• Inability to swallow oral medications or the presence of gastrointestinal dysfunction or disease that may significantly alter drug absorption.
• A history of another malignancy within 2 years prior to the first dose, histologically distinct from the cancer under study, except for carcinoma in situ of the cervix, superficial non-invasive bladder cancer, or adequately treated stage I non-melanoma skin cancer.
• Prior treatment with KRAS G12C inhibitors, KRAS G12D inhibitors, pan-KRAS inhibitors, or other agents of the same class.
• Primary central nervous system (CNS) tumors.
• Women who are pregnant or breast-feeding.
• Participants who have progressive disease or recurrence during neoadjuvant or adjuvant treatment, or within 6 months after the last dose of medication.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 13 центров

• Beijing Cancer Hospital — Пекин
• Zhejiang Cancer Hospital — Ханчжоу
• Beijing Tsinghua Changgung Hospital — Пекин
• Hunan Cancer Hospital — Чанша
• Harbin Medical University Cancer Hospital — Харбин
• Jiangsu Province Hospital — Нанкин
• Shanghai Jiaotong University School of Medicine Ruijin Hospital — Шанхай
• ShanXi Cancer Hospital — Taiyuan
• … и ещё 5 центров

Идентификаторы

NCT: NCT07640295 · JAB-23E73-2001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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