This is a Multicenter, Open-label, Phase I/II Study to Explore the Safety, Tolerability, Pharmacokinetics (PK), and Preliminary Efficacy of GFH276 in Patients With Advanced NSCLC Harboring a RAS Mutation. (GFH276X1203)
A Phase Ib/II, Multicenter, Open-Label Study To Evaluate Safety, Efficacy And Pharmacokinetics Of GFH276 In Combination With Tislelizumab, Pemetrexed And Platinum (Carboplatin Or Cisplatin) As First-Line Therapy In Participants With Locally Advanced Or Metastatic Non-Squamous Non-Small-Cell Lung Cancer Harboring RAS Mutation
This is an open-label, multicenter Phase Ib/II clinical study evaluating GFH276 in combination with tislelizumab plus pemetrexed/platinum based regimen as first-line therapy in participants with locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC) harboring RAS mutation or KRAS amplification.
연구 개요
상태
상세 설명
This open-label, multicenter Phase Ib/II study enrolls participants with locally advanced or metastatic non-squamous NSCLC with RAS mutation or KRAS amplification, who have not received prior systemic anti-cancer therapy for advanced disease.
In Phase Ib, dose escalation of GFH276 will be performed in assigned arm to identify the recommended Phase 2 dose (RP2D) based on dose-limiting toxicity (DLT) and the overall safety profile. After RP2D determination, participants will be enrolled in Phase II to further evaluate the anti-tumor efficacy and long-term safety of each combination regimen. Study-related assessments will include tumor imaging, laboratory tests, adverse event monitoring, and pharmacokinetic sampling throughout the treatment period.
Participants will continue their assigned study treatment until confirmed disease progression, intolerable toxicity, withdrawal of consent, or study closure.
연구 유형
등록 (추정된)
단계
- 2 단계
- 1단계
연락처 및 위치
연구 연락처
- 이름: Li Bai
- 전화번호: +86 2168821388
- 이메일: lbai@genfleet.com
연구 연락처 백업
- 이름: Pingping Zhang
- 전화번호: +86 2168821388
- 이메일: ppzhang@genfleet.com
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Histologically/cytologically confirmed locally advanced or metastatic non squamous NSCLC (AJCC 8th edition Stage IIIB-IV).
- Confirmed RAS mutation or KRAS amplification；tumor cell PD L1 test report available
- No prior systemic anti-tumor therapy for advanced disease
- At least 1 measurable lesion outside the central nervous system (CNS) per RECIST v1.1
- ECOG performance status 0 or 1
- Life expectancy>3 months
- Willing to provide written informed consent
- Fertile participants must use effective contraception
- Adequate organ function
Exclusion Criteria:
- Other active malignancy within 3 years
- Symptomatic brain metastases, leptomeningeal disease, spinal cord compression, or primary brain tumor
- History of active clinically significant cardiovascular dysfunction
- Known to harbor other targetable driver gene alterations
- Presence of active infection (HIV, HBV, HCV,)
- Prior anti-tumor therapy within 28 days or 5 half-lives
- Diagnosis of unstable thrombotic events requiring therapeutic intervention within 3 months prior to the first dose of study treatment.
- Hypersensitivity to study drugs, or inability to swallow tablets or comply with study procedures.
- History of central nervous system (CNS)disease
- Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonia that requires treatment.
- With uncontrollable or symptomatic pleural effusion, ascites, or pericardial effusion.
- Active autoimmune disease requiring systemic treatment.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: GFH276 ±Tislelizumab + AP
GFH276 once daily; Tislelizumab 200 mg, IV; AP: Pemetrexed 500 mg/m², IV; Cisplatin/Carboplatin 75 mg/m²/AUC=5, IV, every 3 weeks |
Oral GFH276, administered at specified dose on schedule. Tislelizumab 200 mg, intravenous infusion, once every 3 weeks.or without Tislelizumab Pemetrexed 500 mg/m², intravenous infusion, once every 3 weeks. Cisplatin 75 mg/m², intravenous infusion, once every 3 weeks. Carboplatin at AUC=5, intravenous infusion, once every 3 weeks. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events
기간: First 21 days
|
The incidence of DLT events |
First 21 days
|
|
Phase II:Objective Response Rate (ORR)
기간: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Assessed by investigators according to RECIST 1.1 |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
Phase Ib:Incidence and Severity of Adverse Events (AE) and Serious Adverse Events (SAE)
기간: From the first dose until 30 days after the last dose, assessed up to 36 months
|
The incidence and severity of AEs and SAEs，according to NCI CTCAE，v6.0 |
From the first dose until 30 days after the last dose, assessed up to 36 months
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
DCR
기간: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Disease Control Rate (DCR) |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
DoR
기간: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Duration of Response assessed by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
TTR
기간: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Time To Response assessed by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
PFS
기간: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Progression-Free Survival (PFS) per Response Evaluation Criteria according to RECIST 1.1, as Determined by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
OS
기간: From the first dose until date of death from any cause, assessed up to 36 months
|
Overall Survival |
From the first dose until date of death from any cause, assessed up to 36 months
|
|
Phase II: Incidence and Severity of AE and SAE
기간: From the first dose until 30 days after the last dose, assessed up to 36 months
|
Incidence and Severity of AE and SAE，Assessed according to CTCAE 6.0 |
From the first dose until 30 days after the last dose, assessed up to 36 months
|
공동 작업자 및 조사자
수사관
- 수석 연구원: Ziming Li, MD, Shanghai Chest Hospital
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- GFH276X1203
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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