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XB2001 i kombination med ONIVYDE + 5-FU/LV (+folinsyre) i avanceret bugspytkirtelkræft (1-BETTER)

9. juli 2026 opdateret af: XBiotech, Inc.

Et fase I/II randomiseret, dobbeltblindt, placebokontrolleret forsøg (1-BEDRE) Undersøgelse af XB2001 (Anti-IL-1⍺ Ægte humant antistof) i kombination med ONIVYDE + 5-FU/LV (+folinsyre) i avanceret Kræft i bugspytkirtlen

Dette forsøg vil omfatte 2 portioner (fase 1 og fase 2).

Den første del vil være et fase I, åbent, dosiseskaleringsstudie for at fastslå den maksimalt tolererede dosis (MTD) af XB2001 målt ved dosisbegrænsende toksicitet (DLT), i kombination med ONIVYDE + LV + 5-FU kemoterapiregimen i patienter med fremskreden bugspytkirtelkræft og at bestemme den anbefalede dosis til det efterfølgende fase 2-studie.

Fase 2-delen vil blive implementeret med den maksimalt etablerede tolererede dosis (MTD) af XB2001. Målindskrivningen i fase 2-delen er 60 patienter, som vil blive randomiseret på 1:1-basis til XB2001 plus ONIVYDE + LV + 5-FU (arm 1) eller placebo plus ONIVYDE + LV + 5-FU (arm 2).

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Studietitel: Et fase I/II randomiseret, dobbeltblindt, placebokontrolleret forsøg (1-BETTER), der undersøger XB2001 (anti-IL-1⍺ True Human antistof) i kombination med ONIVYDE + 5-FU/LV (+folinsyre) ) ved fremskreden kræft i bugspytkirtlen

Sponsor: XBiotech USA, Inc.

Studieformand: Benjamin Musher, M.D.

Prøvestørrelse: Ca. 69 patienter vil blive indskrevet i USA (mindst 9 patienter i den åbne fase 1-del og 60 patienter i den randomiserede fase 2-del)

Omtrentlig varighed:

Dette forsøg vil omfatte 2 faser. Den første del vil være et fase I, åbent, dosiseskaleringsstudie, der evaluerer sikkerheden, tolerabiliteten og fastlæggelsen af ​​den maksimale tolererede dosis (MTD) af XB2001 hos mindst ni patienter med metastatisk pancreas-adenokarcinom, som får ONIVYDE + Leucovorin l + d racemisk + 5-Fluorouracil kemoterapi behandling. Varigheden for hver patient i fase I-delen vil være 14 dage (1 behandlingscyklus), hvor de vil blive givet én intravenøs dosis af XB2001 før de får ONIVYDE + Leucovorin l + d racemisk + 5-Fluorouracil kemoterapibehandling og vurderet for dosis Begrænsede toksiciteter (DLT). Fase II-delen vil blive implementeret efter færdiggørelsen af ​​fase I-delen og erklæringen af ​​MTD. Varigheden af ​​forsøgspersonens deltagelse i den randomiserede, dobbeltblindede, placebokontrollerede fase II-del af forsøget er ca. 28 uger: inklusive en screeningsperiode på op til 30 dage og 24 ugers behandlingsperiode. Alle forsøgspersoner kan fortsætte behandlingen med XB2001 i en åben forlængelse, så længe de vurderes at være klinisk gavnlige og ikke har haft uacceptable toksiciteter.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

76

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Arizona
      • Tucson, Arizona, Forenede Stater, 85711
        • Arizona Oncology Associates
    • California
      • Burbank, California, Forenede Stater, 91505
        • Disney Family Cancer Center at Providence St. Joseph Medical Center
      • Cerritos, California, Forenede Stater, 90703
        • TOI Clinical Research
      • Fullerton, California, Forenede Stater, 92835
        • Providence St. Joseph Heritage - Fullerton, CA
      • Newport Beach, California, Forenede Stater, 92663
        • Hoag Memorial Hospital Presbyterian
    • Colorado
      • Grand Junction, Colorado, Forenede Stater, 81505
        • Grand Valley Oncology
    • Florida
      • Lake Mary, Florida, Forenede Stater, 32746
        • Sarah Cannon - Florida Cancer Specialists
      • Miami Beach, Florida, Forenede Stater, 33140
        • Mt. Sinai Comprehensive Cancer Center
      • Sarasota, Florida, Forenede Stater, 34239
        • Sarasota Memorial Hospital
      • Weston, Florida, Forenede Stater, 33331
        • Cleveland Clinic of Florida
    • Indiana
      • Goshen, Indiana, Forenede Stater, 46526
        • Goshen Center for Cancer Care
    • Kansas
      • Merriam, Kansas, Forenede Stater, 66204
        • Alliance for Multispecialty Research, LLC
    • Louisiana
      • New Orleans, Louisiana, Forenede Stater, 70121
        • Ochsner Clinic Foundation
    • Michigan
      • Detroit, Michigan, Forenede Stater, 48201
        • Barbara Ann Karmanos Cancer Institute
      • Farmington Hills, Michigan, Forenede Stater, 48334
        • Revive Research - Farmington Hills
      • Sterling Heights, Michigan, Forenede Stater, 48126
        • Revive Research - Sterling Heights
    • Montana
      • Billings, Montana, Forenede Stater, 59102
        • St. Vincent Frontier Cancer Center
    • New Jersey
      • Florham Park, New Jersey, Forenede Stater, 07932
        • Summit Medical Group
    • New York
      • Stony Brook, New York, Forenede Stater, 11794
        • Stony Brook Cancer Center
      • The Bronx, New York, Forenede Stater, 10461
        • Montefiore Einstein Medical Center
    • Oregon
      • Portland, Oregon, Forenede Stater, 97213
        • Providence Portland
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Forenede Stater, 15232
        • UPMC Hillman Cancer Center
    • Tennessee
      • Knoxville, Tennessee, Forenede Stater, 37920
        • University of Tennessee Medical Center Cancer Institute
      • Nashville, Tennessee, Forenede Stater, 37232
        • Vanderbilt University
      • Nashville, Tennessee, Forenede Stater, 37203
        • Sarah Cannon - Tennessee Oncology
    • Texas
      • Arlington, Texas, Forenede Stater, 76012
        • Texas Oncology - Arlington
      • Dallas, Texas, Forenede Stater, 75230
        • Mary Crowley Cancer Research
    • Utah
      • Ogden, Utah, Forenede Stater, 84405
        • Community Cancer Trials of Utah
    • Virginia
      • Fairfax, Virginia, Forenede Stater, 22031
        • Virginia Cancer Specialists
      • Midlothian, Virginia, Forenede Stater, 23114
        • Bon Secours St. Francis Cancer Center

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Beskrivelse

Inklusionskriterier:

  • Histologisk eller cytologisk bekræftet pancreas adenocarcinom i eksokrin pancreas, der er metastatisk, ikke-operabelt eller tilbagevendende
  • Mindst én målbar læsion i henhold til responsevalueringskriterier i solid tumor V1.1
  • Dokumenteret sygdomsprogression efter én tidligere gemcitabin-baseret behandling ELLER én FOLFIRINOX og gemcitabin kombinationsbehandling
  • Eastern Cooperative Oncology Group (ECOG) præstation på 0 eller 1 eller Karnofsky præstationsstatus (KPS) ≥ 70
  • Tilstrækkelig lever-, nyre- og knoglemarvsfunktion

Ekskluderingskriterier:

  • Klinisk signifikant fald i præstationsstatus (lægejournaler) inden for 2 uger efter påtænkt første dosisadministration
  • Klinisk signifikante GI lidelser
  • Alvorlige arterielle tromboemboliske hændelser mindre end 6 måneder før inklusion
  • Forudgående strålebehandling af hele hjernen (WBRT)
  • Bevis på hjernemetastaser
  • NYHA klasse III eller IV kongestiv hjertesvigt, ventrikulære arytmier eller ukontrolleret blodtryk (defineret som ≥ 160/100 mm Hg)
  • Brug af stærke CYP3A4-inducere eller -hæmmere og/eller UGT1A1-hæmmere inden for 14 dage før besøg 1/baselinebesøg.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Phase I: Dose Escalation Phase

In Phase I (Dose escalation phase), 3 sequential dose levels were administered by participants; 250 mg (dose cohort 1), 500 mg (dose cohort 2), and 1000 mg (dose cohort 3), and traditional 3:3 design was used. Dose-escalation will continue if none of three subjects experience a dose-limiting toxicity (DLT).

After enrollment participants received two treatment cycles (a total of 28 days) in which they were given one intravenous (IV) dose of XB2001 prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
Biologisk: Phase I: XB2001 250 mg
Subjects were administered one intravenous (IV) dose of XB2001 250 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
Andre navne:
  • anti-IL-1⍺ True Human antibody
Biologisk: Phase I: XB2001 500 mg
Subjects were administered one intravenous (IV) dose of XB2001 500 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
Andre navne:
  • anti-IL-1⍺ True Human antibody
Biologisk: Phase I: XB2001 1000 mg
Subjects were administered one intravenous (IV) dose of XB2001 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
Andre navne:
  • anti-IL-1⍺ True Human antibody
Eksperimentel: Phase II: Dose Expansion Phase

In Phase II (dose expansion phase), participants were randomized in 1:1 fashion and received:

  1. XB2001 1000 mg combination with ONIVYDE, Leucovorin, and 5-Fluorouracil
  2. Placebo 1000 mg in combination with ONIVYDE, Leucovorin, and 5-Fluorouracil
Biologisk: Phase II: XB2001 1000 mg
Subjects were administered one intravenous (IV) dose of XB2001 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
Andre navne:
  • anti-IL-1⍺ True Human antibody
Biologisk: Phase II: Placebo
Subjects were administered one intravenous (IV) dose of placebo 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
To Establish the Maximum Tolerated Dose (MTD) of XB2001 as Measured by Dose-Limiting Toxicity (DLT), in Combination With ONIVYDE + LV + 5-FU Chemotherapy Regimen in Patients With Advanced Pancreatic Cancer.
Tidsramme: 28 days (consisting of the first two 14-day treatment cycles or the formal DLT observation window).

The primary objective of the Phase I portion is to identify the MTD of XB2001 when administered in combination with ONIVYDE + LV + 5-FU.

The MTD is defined as the highest dose level at which no more than one out of six subjects experience a DLT. If two or more subjects in a cohort of six experience a DLT, the MTD is considered exceeded, and the previous lower dose level will be identified as the MTD. If no DLTs are observed at the highest dose level studied, that dose will be used for Phase II.

A DLT is defined as any Grade 3-4 adverse event (per NCI CTCAE v5.0) occurring within the first 28 days that is deemed possibly related to the combination regimen, unless the toxicity is clearly attributable to a single non-XB2001 component. Specific DLT criteria include:

  1. Inability to deliver all scheduled doses during the 28-day window due to unexpected drug-related toxicity.
  2. Inability to deliver the intended dose of XB2001 due to drug-related toxicity.
28 days (consisting of the first two 14-day treatment cycles or the formal DLT observation window).
Safety and Tolerability of XB2001 in Combination With ONIVYDE + LV + 5-FU
Tidsramme: From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.

This endpoint evaluates the cumulative safety profile and patient tolerance of XB2001 when administered at the Maximum Tolerated Dose (MTD) or the maximum dose studied in Phase I, in combination with the ONIVYDE + LV + 5-FU regimen.

Safety is characterized by the total number of participants in each cohort who experienced one or more adverse events. For the purpose of this count, each participant is counted only once, regardless of the total number of individual adverse events experienced.
From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Progression Free Survival (PFS)
Tidsramme: From baseline until the date of first documented disease progression or date of death (from any cause), whichever come first.
Progression free survival (PFS) was defined as the time from randomization to first progression based on RECIST v1.1 criteria or death from any cause, whichever occurred first. Subjects who had no baseline and post-baseline tumor assessment and no death, or no adequate post-baseline tumor assessment and no death were censored at the date of randomization. Subjects alive and without documented disease progression at the time of data analysis are censored at the date of the last adequate tumor assessment.
From baseline until the date of first documented disease progression or date of death (from any cause), whichever come first.
Overall Survival (OS)
Tidsramme: From baseline until death from any cause
OS was defined as the duration from the date of randomization until death irrespective of the cause. Subjects who were alive at the time of analysis were censored at the last known date alive. Subjects without any data after baseline were censored on the randomization day.
From baseline until death from any cause
Objective Response Rate (ORR)
Tidsramme: Analyses performed at Visit 5 (Week 8), Visit 9 (Week 16), and Visit 13 (Week 24). This outcome measure was reported for Visit 13.
Objective Response Rate (ORR) is defined as the proportion of subjects in the Phase II Population who achieved a Best Overall Response (BOR) of either Complete Response (CR) or Partial Response (PR), as defined by RECIST v1.1 criteria.
Analyses performed at Visit 5 (Week 8), Visit 9 (Week 16), and Visit 13 (Week 24). This outcome measure was reported for Visit 13.
Time to Treatment Failure(TTF)
Tidsramme: From baseline until treatment failure assessed up to Visit 13 (Week 24)
TTF measures the time from randomization to discontinuation of treatment for any reason, including, but not limited to, disease progression, treatment-related toxicity, and/or death during study.
From baseline until treatment failure assessed up to Visit 13 (Week 24)
Number of Serious Adverse Events (SAEs)
Tidsramme: From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
This outcome measure calculates the total number of unique participants who reported serious adverse events (SAEs) in each group. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
Incidence of Grade 3-4 Diarrhea
Tidsramme: From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
This measure tracks the overall burden of severe (Grade 3) or life-threatening (Grade 4) diarrhea as defined by the NCI CTCAE v5.0. Grade 3 events are severe enough to require medical intervention or significantly limit a person's ability to care for themselves, while Grade 4 events represent urgent, life-threatening clinical situations.
From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
Duration of Hospitalization
Tidsramme: From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
This outcome measure calculates the sum of duration of hospitalizations during the study period in phase II population for both groups.
From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
Plasma Concentration of Natrunix
Tidsramme: Reported results Natrunix: Phase I: V1 post-dose collected at 30 min post-infusion at visit 1(Week 0), which represents Cmax of Cycle 1. Phase II: V6 pre-dose, at Visit 6 (Week 10), represents the trough of steady state concentration.

Measurement of the concentration of Natrunix in plasma samples to evaluate the pharmacokinetic profile.

Due to reporting limitations on this portal, results from only one time point are reported here.

For Phase 1, samples were collected at V1 pre-dose, V1 post-dose, V2 pre-dose, V3 follow up. For phase 2, samples were collected at V1 pre-dose, V1 post-dose, V1 Day 4, V1 Day 7, V2 pre-dose, V3 pre-dose, V4 pre-dose, V6 pre-dose, V8 pre-dose, and V13 follow up. Placebo patients were tested at V1 post-dose only for verification.
Reported results Natrunix: Phase I: V1 post-dose collected at 30 min post-infusion at visit 1(Week 0), which represents Cmax of Cycle 1. Phase II: V6 pre-dose, at Visit 6 (Week 10), represents the trough of steady state concentration.
Number of Treatment Cycles
Tidsramme: From randomization to end of study or study discontinuation for any reasons, up to 24 weeks
This measures the total number of cycles (total number of doses) received by subjects after randomization in each arm.
From randomization to end of study or study discontinuation for any reasons, up to 24 weeks

Andre resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Resultaterne af et symptomspørgeskema vil blive opsummeret efter behandlingsarm på forskellige tidspunkter efter infusion og sammenlignet over tid
Tidsramme: På forskellige tidspunkter efter infusion vurderet op til 22 uger
Score varierer fra 12 til 48. En høj score repræsenterer et dårligere resultat.
På forskellige tidspunkter efter infusion vurderet op til 22 uger
Kardiotoksicitet målt ved antallet af nødvendige EKG'er og kardiotoksicitetsrelaterede hændelser opsummeret af behandlingsarm og sammenlignet over tid
Tidsramme: Sammenlignet over tid, vurderet op til 22 uger
Exploratory Endpoint (kun fase 2-del)
Sammenlignet over tid, vurderet op til 22 uger

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

XBiotech, Inc.

Efterforskere

  • Studiestol: David J Park, Providence St. Joseph Heritage

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

27. maj 2021

Primær færdiggørelse (Faktiske)

26. oktober 2023

Studieafslutning (Faktiske)

10. juni 2025

Datoer for studieregistrering

Først indsendt

24. marts 2021

Først indsendt, der opfyldte QC-kriterier

27. marts 2021

Først opslået (Faktiske)

1. april 2021

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

4. august 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

9. juli 2026

Sidst verificeret

1. juni 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 2020-PT049

Plan for individuelle deltagerdata (IPD)

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INGEN

IPD-planbeskrivelse

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Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

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