Studie af Denikitug (GS-1811) givet alene eller sammen med Nivolumab eller kemoterapi til voksne med metastatisk adenocarcinom i mavesækken, gastroøsofageal overgang (GEJ) og spiserøret
Et fase 2, åbent, multicenter, randomiseret studie til evaluering af Denikitug som monoterapi eller i kombination med Nivolumab eller kemoterapi hos deltagere med HER2-negativ, uoperabel, recidiverende og/eller metastatisk mave-, gastroøsofageal overgangs- (GEJ) og esophageal adenokarcinomer.
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).
Studieoversigt
Status
Intervention / Behandling
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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New South Wales
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Camperdown, New South Wales, Australien, 2050
- Chris O'Brien Lifehouse
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St Leonards, New South Wales, Australien, 2065
- Royal North Shore Hospital
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Queensland
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Herston, Queensland, Australien, 4029
- Royal Brisbane and Women's Hospital
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South Australia
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Bedford Park, South Australia, Australien, 5042
- Flinders Medical Centre
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Western Australia
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Nedlands, Western Australia, Australien, 6009
- Hollywood Private Hospital
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, Forenede Stater, 02215
- Dana Farber Cancer Institute (DFCI)
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New York
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Albany, New York, Forenede Stater, 12206
- New York Oncology Hematology
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New York, New York, Forenede Stater, 10021
- Weill Cornell Medicine - New York Presbyterian Hospital
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Lyon, Frankrig, 69008
- Centre Leon Berard, department of medical oncology
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Marseille, Frankrig, 13009
- Institut Paoli-Calmettes, department of medical oncology
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Barcelona, Spanien, 8035
- Hospital Universitari Vall d'Hebron
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Madrid, Spanien, 28041
- Hospital Universitario 12 de Octubre
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Pamplona, Spanien, 31008
- Hospital Universitario de Navarra
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Valencia, Spanien, 46010
- Hospital Clinico Universitario de Valencia
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Seoul, Sydkorea, 03830
- Seoul National University Hospital
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: 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
Andre navne:
Administered Intravenously |
|
Eksperimentel: 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
Andre navne:
Administered Intravenously |
|
Eksperimentel: Part 1: Arm C: DEN (Dose B)
Participants will receive DEN Dose B as an IV infusion. |
Administered Intravenously
Andre navne:
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Eksperimentel: 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
Andre navne:
Administered Intravenously Administered Intravenously |
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Eksperimentel: 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
Andre navne:
Administered Intravenously Administered Intravenously |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Objective Response Rate (ORR)
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Procentdel af deltagere, der oplever behandlingsrelaterede bivirkninger ifølge National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Tidsramme: Første dosis dato op til 120 dage efter sidste dosis, op til 4 år.
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Første dosis dato op til 120 dage efter sidste dosis, op til 4 år.
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Andel af deltagere, der oplever kliniske laboratorieabnormiteter i henhold til NCI CTCAE v5.0
Tidsramme: Første dosisdato op til 120 dage efter sidste dosis, op til 4 år.
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Første dosisdato op til 120 dage efter sidste dosis, op til 4 år.
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Farmacokinetisk (FK) parameter: Serumkoncentration af DEN
Tidsramme: Op til 4 år
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Op til 4 år
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Andel af deltagere, der udviklede behandlingsfremkaldte antidrug-antistoffer (ADA) mod Denikitug
Tidsramme: Op til 4 år
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Op til 4 år
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Duration of Response (DOR)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Studieleder: Gilead Study Director, Gilead Sciences
Publikationer og nyttige links
Hjælpsomme links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Adenocarcinom i spiserøret
- Aminosyrer, peptider og proteiner
- Proteiner
- Organiske kemikalier
- Kulbrinter
- Cycloparaffiner
- Kulbrinter, alicyklisk
- Kulbrinter, cyklisk
- Terpenes
- Antistoffer, monoklonal, humaniseret
- Antistoffer, monoklonal
- Antistoffer
- Immunoglobuliner
- Immunoproteiner
- Blodproteiner
- Serum globuliner
- Globuliner
- Taxoider
- Cyclodecanes
- Diterpenes
- Nivolumab
- Ramucirumab
- Paclitaxel
Andre undersøgelses-id-numre
- GS-US-742-7757
- 2025-524095-27 (Anden identifikator: EU Trial (CTIS) Number)
- 2025 (U.S. NIH-bevilling/kontrakt)
- CTR20263204 (Anden identifikator: China's Center for Drug Evaluation)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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