Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation

Официальное название

A Phase 1/2a Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of JAB-21822 in Combination With JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation

Обзор

This is a multicenter, open-label phase 1/2a study consisting of two parts: dose escalation phase and dose expansion phase. The objective of the dose escalation phase is to evaluate the safety, tolerability and pharmacokinetics of JAB-21822 in combination with JAB-3312 in patients with advanced solid tumors harboring KRAS p.G12C mutation and to determine the RP2D for the combination therapy. In the dose expansion phase, preliminary efficacy and safety of the combination therapy at the RP2D will be further explored in patients with specific cancer harboring KRAS p.G12C mutation.

Вмешательства

• Препарат JAB-21822
  KRAS G12C inhibitor
• Препарат JAB-3312
  SHP2 inhibitor

Первичные конечные точки

• recommended phase-2 dose (RP2D). [Срок оценки: Approximately 2 years]
• Number of participants with dose limiting toxicities [Срок оценки: Approximately 2 years]

Вторичные конечные точки (3)

• Number of participants with AEs [Срок оценки: Approximately 2 years]
• Objective response rate (ORR) [Срок оценки: Approximately 2 years]
• Progression-free survival (PFS) [Срок оценки: Approximately 2 years]

Критерии участия

Критерии включения

• A written informed consent should be signed by a subject or his/her legal representative before any study-related procedures are performed;
• Subjects with histologically or cytologically confirmed locally advanced or metastatic advanced solid tumors harboring KRAS p.G12C mutation who have failed or lack standard-of-care (SOC) or are unwilling to undergo or intolerant to SOC;
• Expected survival ≥ 3 months;
• Subjects must have at least one measurable lesion as defined by RECIST v1.1. If no measurable lesion untreated with radiation is selected as the target lesion, a lesion treated with radiation ≥ 4 weeks before the first dose and with progression confirmed by radiography may be selected as the target lesion;
• Eastern Cooperative Oncology Group(ECOG) performance status 0-1;
• The organ functions of subjects meet the criteria for the following laboratory parameters at screening;
• Subjects must be able to swallow oral medications without gastrointestinal abnormalities that significantly affect drug absorption

Критерии исключения

• Patients with previous (≤ 3 years) or current tumors of other pathological types, except for cured cervical carcinoma in situ, ductal carcinoma in situ of the breast, prostatic intraepithelial neoplasia, superficial non-invasive bladder cancer, stage I skin cancer (except melanoma); subjects without recurrence or metastasis for > 3 years after treatment, without current evidence of tumor, and without significant risk of recurrence of previous malignant diseases in the opinion of the study doctor may also be enrolled;
• Serious allergy to the investigational drug or excipients (such as microcrystalline cellulose, etc.);
• Patients with previous (≤ 6 months before the initiation of treatment) or current severe autoimmune diseases (including adverse reactions caused by previous anti- tumor immunotherapies), or autoimmune diseases requiring long-term systemic hormone therapy at immunosuppressive dose levels (prednisone > 10 mg/day or equivalent drugs);
• HIV, hepatitis B virus(HBV), or hepatitis C virus(HCV) positive;
• Previous (≤ 6 months prior to the first dose) or current evidence of the following diseases: acute myocardial infarction, unstable angina and cerebrovascular accident;
• Subjects who have impaired cardiac functions or clinically significant cardiac diseases;
• Pregnant or lactating women

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 27 центров

• The First Affiliated Hospital of USTC Anhui Provincial Hospital — Хэфэй
• Pecking Union Medical College Hospital — Пекин
• Cancer Hospital Chinese Academy Of Medical Sciences — Пекин
• Beijing Tiantan Hospital, Captal Medical University — Пекин
• Beijing Cancer Hospital — Пекин
• Peking University Third Hospital — Пекин
• Beijing Chest Hospital, Capital Medical University — Пекин
• Fujian cancer Hospital — Фучжоу
• … и ещё 19 центров

Публикации

• Zhong J, Zhao J, Duan J, Fang J, Fei K, Li X, Chen J, Wang Z, Chu Q, Yu Y, Liu Z, Zhang L, Zhao Y, Li X, Wu L, Xing L, Zhuang W, Fang X, Chang J, Pan Y, Dong X, Liu L, Bai C, Pan P, Song Q, Jin B, Cao B, Ye F, Shi J, Tang K, Wang-Gillam A, Ding Y, Bi C, Shao Y, Pang J, Wan R, Sun B, Xu J, Wang J; JAB-21822-1006 Study Group. Glecirasib plus sitneprotafib in patients with KRASG12C-mutated non-small- PMID 41325755
• Kang D, Wang Y, Lin Y, Ma WW, Morgensztern D, Leventakos K, Bi C, Ding Y, Xiong J, Yan M, Sun X, Wang P, Ma C, Wang Y. JAB-3312, a Potent Allosteric SHP2 Inhibitor That Enhances the Efficacy of RTK/RAS/MAPK and PD-1 Blockade Therapies. Clin Cancer Res. 2025 Jul 15;31(14):3019-3032. doi: 10.1158/1078-0432.CCR-24-3691. PMID 40333694

Идентификаторы

NCT: NCT05288205 · JAB-21822-1006

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗