Studie av Denikitug (GS-1811) gitt alene eller med nivolumab eller kjemoterapi hos voksne med metastatisk gastrisk, gastroøsofagealt overgangs (GEJ) og esofagealt adenokarsinom
En fase 2, åpen, multisenter, randomisert studie for å evaluere Denikitug som monoterapi eller i kombinasjon med Nivolumab eller kjemoterapi hos deltakere med HER2-negativ, ikke-resektabel, residiverende og/eller metastatisk adenokarsinom i mage, gastroøsofagal overgang (GEJ) og spiserør
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).
Studieoversikt
Status
Intervensjon / Behandling
Studietype
Registrering (Antatt)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
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New South Wales
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Camperdown, New South Wales, Australia, 2050
- Chris O'Brien Lifehouse
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St Leonards, New South Wales, Australia, 2065
- Royal North Shore Hospital
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Queensland
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Herston, Queensland, Australia, 4029
- Royal Brisbane and Women's Hospital
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South Australia
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Bedford Park, South Australia, Australia, 5042
- Flinders Medical Centre
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Western Australia
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Nedlands, Western Australia, Australia, 6009
- Hollywood Private Hospital
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Massachusetts
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Boston, Massachusetts, Forente stater, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, Forente stater, 02215
- Dana Farber Cancer Institute (DFCI)
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New York
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Albany, New York, Forente stater, 12206
- New York Oncology Hematology
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New York, New York, Forente stater, 10021
- Weill Cornell Medicine - New York Presbyterian Hospital
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Lyon, Frankrike, 69008
- Centre Leon Berard, department of medical oncology
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Marseille, Frankrike, 13009
- Institut Paoli-Calmettes, department of medical oncology
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Barcelona, Spania, 8035
- Hospital Universitari Vall d'Hebron
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Madrid, Spania, 28041
- Hospital Universitario 12 de Octubre
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Pamplona, Spania, 31008
- Hospital Universitario de Navarra
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Valencia, Spania, 46010
- Hospital Clinico Universitario de Valencia
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Seoul, Sør -Korea, 03830
- Seoul National University Hospital
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
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 studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: 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 navn:
Administered Intravenously |
|
Eksperimentell: 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 navn:
Administered Intravenously |
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Eksperimentell: Part 1: Arm C: DEN (Dose B)
Participants will receive DEN Dose B as an IV infusion. |
Administered Intravenously
Andre navn:
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Eksperimentell: 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 navn:
Administered Intravenously Administered Intravenously |
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Eksperimentell: 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 navn:
Administered Intravenously Administered Intravenously |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
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 |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Andel deltakere som opplever behandlingsrelaterte bivirkninger (TEAE) i henhold til National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) versjon 5.0
Tidsramme: Første doseringsdato opptil 120 dager etter siste dose, opptil 4 år.
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Første doseringsdato opptil 120 dager etter siste dose, opptil 4 år.
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Andel deltakere som opplever kliniske laboratorieavvik i henhold til NCI CTCAE v5.0
Tidsramme: Første dose dato opptil 120 dager etter siste dose, opptil 4 år.
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Første dose dato opptil 120 dager etter siste dose, opptil 4 år.
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Farmakokinetisk (PK) parameter: Serumkonsentrasjon av DEN
Tidsramme: Opptil 4 år
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Opptil 4 år
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Prosentandel av deltakere som utviklet behandlingsindusert antilegemiddelantistoff (ADA) mot Denikitug
Tidsramme: Opptil 4 år
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Opptil 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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Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Studieleder: Gilead Study Director, Gilead Sciences
Publikasjoner og nyttige lenker
Hjelpsomme linker
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Adenokarsinom i spiserøret
- Aminosyrer, peptider og proteiner
- Proteiner
- Organiske kjemikalier
- Hydrokarboner
- Cycloparaffins
- Hydrokarboner, alicyklisk
- Hydrokarboner, syklisk
- Terpener
- Antistoffer, monoklonalt, humanisert
- Antistoffer, monoklonalt
- Antistoffer
- Immunoglobuliner
- Immunoproteiner
- Blodproteiner
- Serumglobuliner
- Globuliner
- Taxoider
- Cyclodecanes
- Diterpenes
- Nivolumab
- Ramucirumab
- Paclitaxel
Andre studie-ID-numre
- GS-US-742-7757
- 2025-524095-27 (Annen identifikator: EU Trial (CTIS) Number)
- 2025 (U.S. NIH-stipend/kontrakt)
- CTR20263204 (Annen identifikator: China's Center for Drug Evaluation)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Legemiddel- og utstyrsinformasjon, studiedokumenter
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