Phase 1b Study of ORIC-114 in Combination With Amivantamab in Patients With EGFR Exon20 Insertion Mutant NSCLC
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 76
- 试验地点
- 8
- 主要终点
- Recommended Phase 2 Dose (RP2D)
研究概览
简要总结
The purpose of this study is to establish the recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of ORIC-114 in combination with subcutaneous (SC) amivantamab in patients with advanced or metastatic NSCLC harboring an EGFR exon 20 insertion mutation.
详细描述
ORIC-114, is a brain penetrant, selective, orally bioavailable, irreversible small molecule inhibitor designed to target EGFR exon 20 insertion mutations, making it a promising therapeutic candidate for development in patients whose tumors harbor these alterations, including those with CNS metastases.
Amivantamab is a bispecific EGFR-directed and MET receptor-directed antibody indicated in combination with carboplatin and pemetrexed for the first line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations and also as a single agent in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.
This is an open-label, single arm, multicenter, dose escalation followed by dose expansion study to assess the safety and preliminary antitumor activity of ORIC-114 in combination with SC amivantamab, in patients with locally advanced or metastatic NSCLC harboring an EGFR exon 20 insertion mutations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed metastatic NSCLC with a documented EGFR exon 20 insertion mutation as determined locally by any nucleic acid-based diagnostic testing method; all tests should be performed in a CLIA certified or equivalently accredited laboratory
- •Prior Therapies:
- •Dose Escalation: Patients may have previously received and progressed on or after platinum-based chemotherapy or may be treatment naïve
- •Dose Expansion: Patients must not have received any prior therapy; at time of enrollment, patients must decline, or be ineligible for all available standard of care therapies with proven benefit
- •Agreement and ability to undergo a pretreatment biopsy, provided the procedure is clinically feasible and not deemed unsafe by the investigator
- •Measurable disease according to RECIST 1.1
- •Patients with asymptomatic CNS metastases are eligible
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate organ function
排除标准
- •Known small cell lung cancer transformation
- •Leptomeningeal disease
- •Spinal cord compression not definitively treated with surgery or radiation
- •Prior immunotherapy
- •Past medical history of interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
- •Active gastrointestinal disease (eg, Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably impact absorption of ORIC-114
研究组 & 干预措施
Part 1 Dose Escalation level 1
ORIC-114 + amivantamab
干预措施: ORIC-114 Dose 1 + amivantamab (Drug)
Part 1 Dose Escalation level 2
ORIC-114 + amivantamab
干预措施: ORIC-114 Dose 2 + amivantamab (Drug)
Part 1 Dose Escalation level 3
ORIC-114 + amivantamab
干预措施: ORIC-114 Dose 3 + amivantamab (Drug)
Part 2 Dose Expansion
Two potential ORIC-114 dose levels + amivantamab
干预措施: ORIC-114 Dose 2 + amivantamab (Drug)
Part 2 Dose Expansion
Two potential ORIC-114 dose levels + amivantamab
干预措施: ORIC-114 Dose 3 + amivantamab (Drug)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D)
时间窗: 12 months
RP2D of ORIC-114 in combination with amivantamab by interval 3+3 dose escalation design
Objective response rate (ORR)
时间窗: 12 months
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Progression-free survival (PFS)
时间窗: 12 months
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Duration of response (DOR)
时间窗: 12 months
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
次要结局
- Intracranial Objective response rate (ORR)(12 months)
- BICR-Duration of response (DOR)(12 months)
- BICR-Objective response rate (ORR)(12 months)
- BICR-Progression-free survival (PFS)(12 months)
- Intracranial Progression-free survival (PFS)(12 months)
- Plasma PK parameters(28 Days)