癌研連線CancerLink
招募中 NCT05315700

ORIC-114在伴有EGFR或HER2变化的晚期实体瘤患者中的研究

非小细胞肺癌乳腺癌Phase IIII 期IV 期EGFRHER2

本研究的目的是确定ORIC-114作为单一药物或与化疗联合使用时给予伴有EGFR或HER2变化的晚期实体肿瘤患者的建议2期剂量(RP2D)和/或最大耐受剂量(MTD)、安全性、药物动力学(PK)、药效学(PD)和抗肿瘤活性。

适应症：Solid Tumors

入组条件

纳入标准

  • Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented EGFR or HER2 exon 20 insertion mutation or atypical EGFR mutation as determined by any nucleic acid-based diagnostic testing method, or HER2 amplification/overexpression as determined by an immunohistochemistry (IHC) or an in situ hybridization (ISH) test
  • Part I Dose Escalation (CLOSED) Any solid tumor with
  • EGFR exon 20 insertion mutation
  • HER2 exon 20 insertion mutation
  • Atypical EGFR mutations (NSCLC only) (Appendix 8)
  • HER2 amplification or overexpression (HER2+)
  • Previously received and progressed on or after available standard therapies and for whom additional standard therapy is considered unsuitable or intolerable
  • Part I Extension (ONGOING)
  • Cohort IA: Patients with HER2+ breast cancer previously received and progressed on or after available standard therapies and for whom additional standard therapy is considered unsuitable or intolerable
  • Cohort IB: NSCLC patients with EGFR exon 20 insertion mutation previously treated with chemotherapy and amivantamab
  • Cohort IC: Treatment-naïve NSCLC patients with EGFR exon 20 insertion mutation
  • Cohort ID: Treatment-naïve NSCLC patients with EGFR atypical mutations
  • Part II Dose Optimization (ONGOING): NSCLC patients with
  • Cohort IIA: EGFR exon 20 insertion mutation, patients must have received platinum-based chemotherapy or other chemotherapy regimen if platinum- based chemotherapy was contraindicated. Additionally, patients must be naïve to an EGFR exon 20 targeted agent, ie, must have declined or be ineligible for all available exon 20 targeted therapies with proven benefit
  • Cohort IIB: HER2 exon 20 insertion mutation, patients must have received platinum-based chemotherapy or other chemotherapy regimen if platinum- based chemotherapy was contraindicated. Additionally, patients must be naïve to a HER2 exon 20 targeted TKI
  • Cohort IIC: Atypical EGFR mutation, patients may have received a prior EGFR TKI
  • Agreement and ability to undergo pretreatment biopsy
  • Measurable disease according to RECIST 1.1
  • CNS involvement, which is either previously treated and controlled, or untreated and asymptomatic
  • ECOG performance status of 0 or 1
  • Adequate organ function

排除标准

  • Known EGFR T790M mutation
  • Leptomeningeal disease and spinal cord compression
  • \-- Except if LMD has been reported radiographically on baseline MRI, but is not suspected clinically by the Investigator; the subject must be free of neurological symptoms of LMD
  • History of class III or IV congestive heart failure or severe non-ischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months
  • Past medical history of interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
  • Known, symptomatic human immunodeficiency virus (HIV) infection
  • Known active infection requiring treatment or history of hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients positive for HBsAg but normal HBV DNA level are allowed.
  • Active gastrointestinal disease (eg, Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes
  • Any other concurrent serious uncontrolled medical, psychological, or addictive conditions

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。