癌研連線CancerLink
已完成 NCT04526106

REFOCUS：高度选择性 FGFR2 抑制剂 RLY-4008 于 ICC 及其他晚期实体瘤患者中的首次人体研究

胆道癌Phase IIII 期IV 期

这是一项第一期/第二期、开放标签、首次人体（FIH）研究，旨在评估 RLY-4008（一种强效且高度选择性的 FGFR2 抑制剂）在不可切除或转移性胆管癌（CCA）及其他实体瘤患者中的安全性、耐受性、药物动力学（PK）、药效学（PDy）及抗肿瘤活性。本研究包括 4 个部分：剂量递增（第 1 部分）、剂量扩展（第 2 部分）、延伸（第 3 部分）及滚动（第 4 部分）。

适应症：FGFR2 Amplification、FGFR2 Gene Mutation、FGFR2 Gene Fusion/Rearrangement、FGFR2 Gene Translocation、FGFR2 Gene Activation、Intrahepatic Cholangiocarcinoma、Cholangiocarcinoma、Other Solid Tumors, Adult

入组条件

纳入标准

  • Histologically or cytologically confirmed unresectable or metastatic solid tumor
  • Documented FGFR2 gene fusion, mutation, or amplification per local testing of blood and/or tumor
  • Patient must have measurable disease per RECIST v1.1
  • Patient has ECOG performance status of 0-1
  • Patient must have disease that is refractory to standard therapy, disease that has not adequately responded to standard therapy, disease for which standard or curative therapy does not exist, or the patient must be intolerant to or have declined standard therapy
  • Part 2 dose expansion patients with Cholangiocarcinoma:
  • Group 1: CCA patients with an FGFR2 fusion previously treated with an FGFRi
  • Group 2: CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi
  • Group 6: CCA patients with an FGFR2 fusion with no prior chemotherapy and not previously treated with an FGFRi. Prior adjuvant/neo-adjuvant treatment completed \>6 months before enrollment is acceptable. Up to 2 cycles of palliative chemotherapy are allowed during screening
  • Group 7: CCA patients with an FGFR2 mutation or amplification and not previously treated with an FGFRi. Note: For Group 7, patients with confirmed diagnosis of unresectable or metastatic CCA with an FGFR2 fusion are not eligible.
  • Part 2 dose expansion patients with other solid tumors (NOT Cholangiocarcinoma):
  • Group 3: Non-CCA patients with an FGFR2 fusion and not previously treated with an FGFRi.
  • Group 4: Non-CCA patients with an FGFR2 amplification and not previously treated with an FGFRi.
  • Group 5: Non-CCA patients with an FGFR2 mutation and not previously treated with an FGFRi
  • Part 3 extension:
  • o CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi
  • Part 4:
  • Patient is receiving RLY-4008 on RLY-4008-101 study and benefiting from treatment as assessed by the investigator.

排除标准

  • Parts 1, 2, and 3
  • Ongoing, clinically significant FGFRi-induced retinal detachment or an ongoing clinically significant corneal or retinal disorder
  • Patient does not have adequate organ function (defined in protocol)
  • Patient has active infection, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV) (defined in protocol). Patients with well-controlled HBV are eligible (defined in protocol).
  • QT interval corrected using Fridericia\'s formula (QTcF) \> 480 msec or history of prolonged QT syndrome, Torsades de pointes or familial history of prolonged QT syndrome
  • Clinically significant, uncontrolled cardiovascular disease
  • CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms
  • Part 4:
  • Patient has permanently discontinued treatment with RLY-4008 for any reason before enrolling into Part 4.

入组条件维持 ClinicalTrials.gov 原始英文登记资料，实际入组资格以研究团队的正式评估与受试者知情同意书为准。资料来源：ClinicalTrials.gov，每两周自动更新，最后同步：2026年10月8日。