데니키투그(GS-1811) 단독 투여 또는 Nivolumab이나 화학요법과 병용 투여에 대한 전이성 위암, 위식도접합부(GEJ) 및 식도 선암종 성인 환자 대상 연구
2상, 공개, 다기관, 무작위 배정 임상시험: HER2 음성 절제 불가능, 재발성 및/또는 전이성 위암, 위식도 접합부(GEJ) 선암 및 식도 선암 환자를 대상으로 Denikitug 단독요법 또는 Nivolumab 또는 화학요법과의 병용요법을 평가하는 연구
The goal of this clinical study is to learn more about the study drug, Denikitug (DEN, GS-1811), to evaluate the efficacy and safety of Denikitug Monotherapy and Denikitug-based combinations in in participants with human epidermal growth factor receptor 2 (HER2)-Negative, unresectable, recurrent, and/or metastatic, gastroesophageal junction (GEJ), and esophageal adenocarcinomas.
The primary objective of this study is to assess the effect of DEN as a monotherapy or in combination with nivolumab (NIVO) or ramucirumab (RAM) and paclitaxel (PAC) on objective response rate (ORR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST Version1.1).
연구 개요
상태
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 장소
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Seoul, 대한민국, 03830
- Seoul National University Hospital
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Massachusetts
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Boston, Massachusetts, 미국, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, 미국, 02215
- Dana Farber Cancer Institute (DFCI)
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New York
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Albany, New York, 미국, 12206
- New York Oncology Hematology
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New York, New York, 미국, 10021
- Weill Cornell Medicine - New York Presbyterian Hospital
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Barcelona, 스페인, 8035
- Hospital Universitari Vall d'Hebron
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Madrid, 스페인, 28041
- Hospital Universitario 12 de Octubre
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Pamplona, 스페인, 31008
- Hospital Universitario de Navarra
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Valencia, 스페인, 46010
- Hospital Clinico Universitario de Valencia
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Lyon, 프랑스, 69008
- Centre Leon Berard, department of medical oncology
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Marseille, 프랑스, 13009
- Institut Paoli-Calmettes, department of medical oncology
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New South Wales
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Camperdown, New South Wales, 호주, 2050
- Chris O'Brien Lifehouse
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St Leonards, New South Wales, 호주, 2065
- Royal North Shore Hospital
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Queensland
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Herston, Queensland, 호주, 4029
- Royal Brisbane and Women's Hospital
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South Australia
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Bedford Park, South Australia, 호주, 5042
- Flinders Medical Centre
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Western Australia
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Nedlands, Western Australia, 호주, 6009
- Hollywood Private Hospital
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Key Inclusion Criteria:
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Histologically or cytologically confirmed diagnosis of locally advanced, unresectable, or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma (EAC).
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Human epidermal growth factor receptor 2 (HER2)-negative status, as determined by local assessment using a validated immunohistochemistry assay, in situ hybridization or other amplification testing.
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Has had disease progression during or after first line of systemic therapy for advanced or metastatic gastric, GEJ, or EACs, which must have included at least one of the following:
- Platinum- and fluoropyrimidine-based chemotherapy.
- Therapy with an anti-programmed cell death protein 1 (PD1) or anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibody (patients with PD-L1-positive tumors must have received prior PD-1/PD-L1-based therapy).
- Zolbetuximab or other Claudin-18 (CLDN18).2-targeted therapy, if indicated based on biomarker status.
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Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
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Have adequate organ function.
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Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use methods of contraception.
Key Exclusion Criteria:
- Active or history of autoimmune disease requiring systemic treatment within 2 years, inflammatory bowel disease (IBD) (Crohn's/ulcerative colitis), celiac disease, or noninfectious enteritis/colitis. (Physiologic hormone replacement not considered systemic treatment).
- History or current noninfectious pneumonitis/interstitial lung disease, including radiation-induced pneumonitis requiring steroids or active/recurrent pneumonitis of any etiology.
- Documented microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) disease by local polymerase chain reaction (PCR) (microsatellite status) and/or informed consent form (ICH) (mismatch repair (MMR)) assay
- (For Part 2 only) Has known history of peripheral neuropathy ≥ Grade 2 (per National Cancer Institute(NCI)-Common Tenninology Criteria for Adverse Events (CTCAE) Version 5.0).
- (For Part 2 only) Known coagulopathy that increases the risk of bleeding, bleeding diatheses. Any other Grade 3 or higher hemorrhage/bleeding event within 28 days prior to enrollment.
Prior/Concurrent Therapy or Clinical Study Experience
- Prior treatment with DEN or other C-C chemokine receptor 8 (CCR8)-targeted agents.
- Prior Lonsurf (trifluridine-tipiracil) or paclitaxel (PAC)-based regimens in the first-line setting for advanced/metastatic gastroesophageal adenocarcinoma.
- Any systemic therapy (including investigational) targeting vascular endothelial growth factor (VEGF) or VEGF receptor (VEGFR) signaling pathways.
- Anticancer biologic within 4 weeks, orchemotherapy, targeted small molecule, or radiation therapy within 2 weeks prior to enrollment with unresolved adverse events (AE)s (Grade >2). (Observational study participants are eligible).
- Prior allogenic tissue/solid organ or stem cell transplantation. (Exception: corneal transplant not requiring systemic immunosuppression is allowed).
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Part 1: Arm A: DEN (Dose A) and NIVO
Participants will receive DEN Dose A as an IV infusion in combination with NIVO as an IV infusion. |
Administered Intravenously
다른 이름들:
Administered Intravenously |
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실험적: Part 1: Arm B: DEN (Dose B) and NIVO
Participants will receive DEN Dose B as an IV infusion in combination with NIVO as an IV infusion. |
Administered Intravenously
다른 이름들:
Administered Intravenously |
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실험적: Part 1: Arm C: DEN (Dose B)
Participants will receive DEN Dose B as an IV infusion. |
Administered Intravenously
다른 이름들:
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실험적: Part 2: Arm D: Safety Run-in (SRI) Cohort
Participants will receive DEN in combination with ramucirumab (RAM) and paclitaxel (PAC). If dose for DEN is deemed safe during the SRI Cohort, the study will move forward into the Expansion Period. |
Administered Intravenously
다른 이름들:
Administered Intravenously Administered Intravenously |
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실험적: Part 2: Arm D: Expansion Cohort
If DEN dose is deemed safe in Arm D: SRI Cohort, participants will receive DEN at recommended dose as an IV infusion in combination with RAM and PAC. |
Administered Intravenously
다른 이름들:
Administered Intravenously Administered Intravenously |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Objective Response Rate (ORR)
기간: Up to 4 years
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ORR is defined as the percentage of participants who have achieved complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST Version 1.1. |
Up to 4 years
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Percentage of Participants Experiencing Treatment-Emergent Adverse Event (TEAEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
기간: 마지막 투여 후 최대 120일까지의 첫 투여 날짜, 최대 4년.
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마지막 투여 후 최대 120일까지의 첫 투여 날짜, 최대 4년.
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NCI CTCAE v5.0에 따른 임상 검사 이상을 경험한 참가자의 백분율
기간: 마지막 투여 후 최대 120일 이내의 첫 번째 투여 날짜, 최대 4년.
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마지막 투여 후 최대 120일 이내의 첫 번째 투여 날짜, 최대 4년.
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약동학(PK) 변수: DEN의 혈청 농도
기간: 최대 4년
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최대 4년
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데니키툭에 대한 치료-응급 항약물 항체(ADA)가 발현된 참가자의 비율
기간: 최대 4년
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최대 4년
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Duration of Response (DOR)
기간: Up to 4 years
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DOR is defined as the time of first response CR or PR as assessed by investigator, per RECIST Version 1.1 until the date of first documented progressive disease (PD) or death, whichever comes first. |
Up to 4 years
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Progression-Free Survival (PFS)
기간: Up to 4 years
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PFS is defined as the time from date of first dose until PD or death from any cause, whichever comes first as assessed by the investigator according to RECIST Version 1.1. |
Up to 4 years
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Overall Survival (OS)
기간: Up to 4 years
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OS is defined as the length of time from first dose until the date of death from any cause. |
Up to 4 years
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PK Parameter: Cmax for Denikitug
기간: Up to 4 years
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Cmax is defined as the maximum observed concentration. |
Up to 4 years
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PK Parameter: AUCall for Denikitug
기간: Up to 4 years
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AUCall is defined as the cumulative areas under the curve for all time points. |
Up to 4 years
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공동 작업자 및 조사자
스폰서
수사관
- 연구 책임자: Gilead Study Director, Gilead Sciences
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
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
- GS-US-742-7757
- 2025-524095-27 (기타 식별자: EU Trial (CTIS) Number)
- 2025 (미국 NIH 보조금/계약)
- CTR20263204 (기타 식별자: China's Center for Drug Evaluation)
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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