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En undersøgelse af INCB099280 i kombination med Adagrasib hos voksne med avancerede solide tumorer, der huser en KRASG12C-mutation

3. september 2026 opdateret af: Incyte Corporation

Et fase 1-studie af INCB099280 i kombination med Adagrasib hos voksne med avancerede solide tumorer, der huser en KRASG12C-mutation

Formålet med denne undersøgelse er at evaluere sikkerheden og tolerabiliteten af ​​INCB099280 i kombination med adagrasib og at etablere MTD eller identificere RDE(er) for kombinationen af ​​INCB099280 og adagrasib.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

6

Fase

  • Fase 1

Kontakter og lokationer

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

Studiesteder

  • Det Forenede Kongerige
      • London, Det Forenede Kongerige, W12 0HS
        • Hammersmith Hospital
      • London, Det Forenede Kongerige, SE1 9RT
        • Guys Hospital
  • Forenede Stater
    • California
      • Los Angeles, California, Forenede Stater, 90067
        • Valkyrie Clinical Trials
    • Colorado
      • Greeley, Colorado, Forenede Stater, 80631
        • Banner MD Anderson Cancer Center
    • Michigan
      • Detroit, Michigan, Forenede Stater, 48202
        • Henry Ford Health System
    • Texas
      • Dallas, Texas, Forenede Stater, 75251
        • Mary Crowley Cancer Research Centers McCrc Headquarters
    • Virginia
      • Falls Church, Virginia, Forenede Stater, 22042
        • Inova Schar Cancer Institute
  • Italien
      • Candiolo, Italien, 10060
        • Fondazione Del Piemonte Per L Oncologia Ircc Candiolo
      • Rozzano, Italien, 20089
        • Irccs Istituto Clinico Humanitas
      • Verona, Italien, 37124
        • Centro Ricerche Cliniche Di Verona (Crc)
  • Spanien
      • Barcelona, Spanien, 08035
        • Hospital General Universitario Vall D Hebron
      • Barcelona, Spanien, 08023
        • Hospital HM Nou Delfos
      • Pozuelo de Alarcón, Spanien, 28223
        • Hospital Universitario Quironsalud Madrid
      • Seville, Spanien, 41009
        • Hospital Universitario Virgen Macarena

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

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

Inklusionskriterier:

  • KRASG12C-muteret solid malignitet bestemt ved et sponsorgodkendt assay ved anvendelse af enten tumorvæv eller ctDNA.

  • Histologisk bekræftet malign solid tumor med lokalt fremskreden og/eller metastatisk sygdom.

    • Kun deltagere med NSCLC vil blive tilmeldt del 2 kohorte A.
    • Kun deltagere med CRC vil blive tilmeldt del 2 kohorte B.
  • Del 1: Sygdomsprogression på eller efter mindst 1 tidligere systemisk behandling.
  • Del 2 (Kohorte A - NSCLC): Modtog et anti-PD-(L)1-holdigt regime og platinbaseret kemoterapiregime enten sideløbende eller sekventielt
  • Del 2 (Kohorte B - CRC): Modtaget mindst 1 linje af systemisk terapi, der inkluderer kombinationen af ​​fluoropyrimidin-baseret kemoterapi (i kombination med oxaliplatin og/eller irinotecan) og enten et vaskulært endotelvækstfaktor-målrettet monoklonalt antistof eller et antistof -epidermal vækstfaktor receptor monoklonalt antistof (hvis RAS vildtype). Deltagere med MSI-H/dMMR CRC skal også have modtaget en forudgående immuncheckpoint-hæmmer godkendt til denne indikation.
  • Målbar sygdom i henhold til RECIST v1.1.
  • Eastern Cooperative Oncology Groups præstationsstatus på 0 eller 1.
  • Estimeret forventet levetid > 3 måneder.
  • Vilje til at undgå graviditet.

Ekskluderingskriterier:

  • Kendt yderligere malignitet, der skrider frem eller kræver aktiv behandling.
  • Metastaser i centralnervesystemet (CNS), der kræver behandling og/eller leptomeningeal sygdom.
  • Kun del 2: Forudgående behandling med et godkendt eller forsøgsmiddel rettet mod KRASG12C.
  • Toksicitet fra tidligere behandling, der ikke er nået til protokoldefinerede grænser.
  • Modtog thoraxstråling på > 30 Gy inden for 6 måneder efter den første dosis af undersøgelsesbehandlingen.
  • Deltagelse i en anden interventionel klinisk undersøgelse.
  • Anamnese eller tegn på interstitiel lungesygdom, herunder ikke-infektiøs pneumonitis.
  • Tilstedeværelse af gastrointestinal tilstand, der kan påvirke lægemiddelabsorptionen.
  • Aktiv autoimmun sygdom, der kræver systemisk behandling, inklusive kortikosteroider, der overstiger en daglig dosis på 10 mg prednison eller tilsvarende.
  • Diagnose af immundefekt eller modtage kronisk systemisk steroidbehandling, der overstiger en daglig dosis på 10 mg prednison eller tilsvarende.
  • Aktiv infektion, der kræver systemisk terapi.
  • Historie om organtransplantation, herunder allogen stamcelletransplantation.
  • Modtagelse af systemiske antibiotika inden for 28 dage efter den første dosis af undersøgelsesbehandlingen.
  • Brug af probiotika er forbudt under screening og i hele undersøgelsesbehandlingsperioden.
  • Modtog en levende vaccine inden for 28 dage efter den planlagte start af studielægemidlet.
  • Laboratorieværdier uden for de protokoldefinerede områder.

Andre protokol-definerede inklusions-/eksklusionskriterier kan være gældende.

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: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Del 1: Dosisfinding
INCB099280 administreret i kombination med adagrasib til deltagere med tidligere behandlet KRAS glutamin til cystein mutation ved codon 12 (KRASG12C) mutant fremskredne solide tumorer, vil blive evalueret for at identificere dosis(er) til yderligere evaluering i dosisudvidelsesfasen af ​​studiet.
Medicin: INCB099280
Indgives som specificeret i behandlingsarmbeskrivelsen
Medicin: adagrasib
Indgives som specificeret i behandlingsarmbeskrivelsen
Andre navne:
  • KRAZATI
Eksperimentel: Del 2: Dosisudvidelse
Op til 80 deltagere vil blive tilmeldt 1 af 2 sygdomsspecifikke kohorter: Kohorte A: tidligere behandlet KRASG12C muteret ikke-småcellet lungecancer (NSCLC) Kohorte B: tidligere behandlet KRASG12C-muteret kolorektal cancer (CRC). Op til 3 doser kan vælges fra Del 1: Dosisfinding for Del 2: Dosisudvidelse.
Medicin: INCB099280
Indgives som specificeret i behandlingsarmbeskrivelsen
Medicin: adagrasib
Indgives som specificeret i behandlingsarmbeskrivelsen
Andre navne:
  • KRAZATI

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Dose-limiting Toxicities (DLTs)
Tidsramme: up to Day 28
DLTs were defined as protocol-defined toxicities occurring up to and including on Day 28, except those with a clear alternative explanation. Toxicities with a clear alternative explanation (e.g., due to disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination could have been deemed non-DLTs.
up to Day 28
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Tidsramme: up to 574 days
An adverse event (AE) was defined any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of either study drug until 104 days after the last dose of study treatment or start of new anticancer therapy.
up to 574 days
Number of Participants With TEAEs Leading to Treatment Interruptions, Dose Reductions, and Permanent Discontinuation of INCB099280 and Adagarsib
Tidsramme: up to 574 days
An AE was defined any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of either study drug until 104 days after the last dose of study treatment or start of new anticancer therapy.
up to 574 days

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Concentration of INCB099280
Tidsramme: Lead-in Period Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, and 6
During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered.
Lead-in Period Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, and 6
Cmax of INCB099280 When Administered Alone and in Combination With Adagrasib
Tidsramme: Day -1; Cycle 1 Day 8; Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter
During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered. Cmax was defined as the maximum plasma concentration of INCB099280. Lead-in Period: Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter. Without Lead-in Period: Cycle 1 Day 8: predose and 1, 2, and 4 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter.
Day -1; Cycle 1 Day 8; Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter
Cmax,ss of INCB099280 When Administered Alone and in Combination With Adagrasib
Tidsramme: Day -1; Cycle 1 Day 8; Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter
During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered. Cmax,ss was defined as the maximum plasma concentration of INCB099280 at steady state. Lead-in Period: Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter. Without Lead-in Period: Cycle 1 Day 8: predose and 1, 2, and 4 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter.
Day -1; Cycle 1 Day 8; Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter
Cmin,ss of INCB099280 When Administered Alone and in Combination With Adagrasib
Tidsramme: Day -1; Cycle 1 Day 8; Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter
During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered. Cmin,ss was defined as the minimum plasma concentration of INCB099280 at steady state. Lead-in Period: Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter. Without Lead-in Period: Cycle 1 Day 8: predose and 1, 2, and 4 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter.
Day -1; Cycle 1 Day 8; Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter
Tmax of INCB099280 When Administered Alone and in Combination With Adagrasib
Tidsramme: Day -1; Cycle 1 Day 8; Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter
During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered. tmax was defined as the time to the maximum concentration of INCB099280. Lead-in Period: Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter. Without Lead-in Period: Cycle 1 Day 8: predose and 1, 2, and 4 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter.
Day -1; Cycle 1 Day 8; Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter
AUC0-tau of INCB099280 When Administered Alone and in Combination With Adagrasib
Tidsramme: Day -1; Cycle 1 Day 8; Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter
During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered. AUC0-tau was defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval of INCB099280. Lead-in Period: Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter. Without Lead-in Period: Cycle 1 Day 8: predose and 1, 2, and 4 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter.
Day -1; Cycle 1 Day 8; Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter
CLss/F of INCB099280 When Administered Alone and in Combination With Adagrasib
Tidsramme: Day -1; Cycle 1 Day 8; Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter
During the lead-in period, INCB099280 was administered as monotherapy. During the treatment period, INCB099280 and adagrasib were coadministered. CLss/F was defined as the apparent oral dose clearance of INCB099280 at steady state. Lead-in Period: Day -1 and Cycle 1 Day 8: predose and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter. Without Lead-in Period: Cycle 1 Day 8: predose and 1, 2, and 4 hours postdose; predose on Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter.
Day -1; Cycle 1 Day 8; Day 1 of Cycles 1, 2, 4, 6, 8, 12, and every fourth cycle thereafter
Objective Response
Tidsramme: up to 470 days
Objective response was defined as having a best overall response of complete response (CR) or partial response (PR) assessed per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) by the investigator. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.
up to 470 days
Disease Control
Tidsramme: up to 470 days
Disease control was defined as defined as having a best overall response of CR, PR, or stable disease (SD) ≥15 weeks (from the start of treatment) assessed per RECIST v1.1 by the investigator. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.
up to 470 days
Duration of Response
Tidsramme: up to 470 days
Duration of response was defined as the time from the first CR or PR until disease progression (assessed per RECIST v1.1 by the investigator) or death from any cause, whichever occurred earlier. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.
up to 470 days
Kaplan-Meier Estimate of ≥6-month and ≥12-month Progression-free Survival (PFS)
Tidsramme: ≥6-months and ≥12-months (up to 470 days)
≥6-month and ≥12-month PFS was defined as the absence of disease progression (assessed per RECIST v1.1 by the investigator) or death from any cause from the start of treatment to ≥6 or ≥12 months after treatment. A Kaplan-Meier estimate of PFS is an estimate of the probability that a participant will remain alive and free from disease progression (or relapse) at a given time point after starting treatment.
≥6-months and ≥12-months (up to 470 days)

Samarbejdspartnere og efterforskere

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

Sponsor

Incyte Corporation

Samarbejdspartnere

Mirati Therapeutics Inc.

Efterforskere

  • Studieleder: Incyte Medical Monitor, Incyte Corporation

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)

28. december 2023

Primær færdiggørelse (Faktiske)

11. april 2025

Studieafslutning (Faktiske)

11. juli 2025

Datoer for studieregistrering

Først indsendt

8. september 2023

Først indsendt, der opfyldte QC-kriterier

8. september 2023

Først opslået (Faktiske)

15. september 2023

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

8. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

3. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • INCB99280-204
  • 2023 (U.S. NIH-bevilling/kontrakt: GRAMMY Museum Foundation)
  • 2023-503223-26-00 (Registry Identifier: EU CT number)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

Incyte deler data med kvalificerede eksterne forskere, efter at et forskningsforslag er indsendt. Disse anmodninger gennemgås og godkendes af et bedømmelsespanel på grundlag af videnskabelig fortjeneste. Alle opgivne data er anonymiseret for at respektere privatlivets fred for patienter, der har deltaget i forsøget i overensstemmelse med gældende love og regler. Tilgængeligheden af ​​forsøgsdata er i overensstemmelse med kriterierne og processen beskrevet på https://www.incyte.com/our-company/compliance-and-transparency

IPD-delingstidsramme

Data vil blive delt efter den primære offentliggørelse eller 2 år efter undersøgelsen er afsluttet for markedsgodkendte produkter og indikationer.

IPD-delingsadgangskriterier

Data fra kvalificerede undersøgelser vil blive delt med kvalificerede forskere i henhold til kriterierne og processen beskrevet i afsnittet om datadeling på www.incyteclinicaltrials.com internet side. For godkendte anmodninger vil forskerne få adgang til anonymiserede data i henhold til en datadelingsaftale.

IPD-deling Understøttende informationstype

  • STUDY_PROTOCOL
  • SAP

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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