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Studie av sikkerhet, farmakokinetikk og antitumoraktivitet til BGB-3245 hos deltakere med avanserte eller refraktære svulster

6. juli 2026 oppdatert av: MapKure, LLC

En første-i-menneske, fase 1a/1b, åpen etikett, dose-eskalering og utvidelsesstudie for å undersøke sikkerheten, farmakokinetikken og antitumoraktiviteten til RAF Dimer-hemmeren BGB-3245 hos pasienter med avanserte eller refraktære svulster

Formålet med denne studien er å evaluere sikkerheten, toleransen og antitumoraktiviteten til BGB-3245 hos deltakere med avanserte eller ildfaste solide svulster

Studieoversikt

Status

Avsluttet

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Faktiske)

109

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Australia
    • New South Wales
      • Blacktown, New South Wales, Australia, 2148
        • Blacktown Hospital
      • Sydney, New South Wales, Australia, 2010
        • The Kinghorn Cancer Centre, St Vincent Hospital Sydney
    • Perth
      • Nedlands, Perth, Australia, 6009
        • One Clinical Research
    • Victoria
      • Melbourne, Victoria, Australia, 2010
        • Peter MacCallum Cancer Centre
  • Forente stater
    • California
      • Beverly Hills, California, Forente stater, 90212
        • Cedars Sinai Medical Center
    • Massachusetts
      • Boston, Massachusetts, Forente stater, 02114
        • Massachusetts General Hospital
    • New York
      • New York, New York, Forente stater, 10065
        • Memorial Sloan Kettering Cancer Center
    • Texas
      • Houston, Texas, Forente stater, 77030
        • MD Anderson
    • Virginia
      • Charlottesville, Virginia, Forente stater, 22903
        • University of Virginia Comprehensive Cancer Centre

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Beskrivelse

Viktige inkluderingskriterier:

  1. Deltakere med histologisk bekreftet avansert eller metastatisk solid svulst som har hatt sykdomsprogresjon under eller etter minst 1 linje med tidligere systemisk kreftbehandling, eller som behandling ikke er tilgjengelig eller ikke tolerert/akseptabelt for deltakerne. I tillegg må deltakerne oppfylle følgende kvalifikasjonskriterier for den tilsvarende fasen av studien:

    en. Fase 1a: deltakere med kjent mutasjonsstatus og svulst som huser en onkogen mutasjon av v-RAF murine sarcoma virale onkogen homolog B (BRAF) genet (mutasjonene av primær interesse er BRAF klasse II mutasjon, klasse

    III-mutasjon eller BRAF-fusjon). I tillegg er deltakere med svulster som inneholder mutasjonen av neuroblastom RAS viral onkogen homolog (NRAS) genet eller Kirsten rotte sarkom virus onkogen homolog (KRAS) kvalifisert for del 1a. For pasienter med KRAS-mutasjoner er tumortyper av tykktarmskreft (CRC) og kreft i bukspyttkjertelen ekskludert. Fase 1b: deltakere må ha en kjent mutasjonsstatus og oppfylle ett av følgende kriterier i henhold til gruppen de er registrert i:

    I. Gruppe 1: Pasienter med andre tumortyper enn tykktarmskreft (CRC) som har BRAF V600-mutasjoner som har blitt behandlet og utviklet seg med tidligere BRAF- og/eller mitogenaktivert proteinkinase- (MEK)-hemming.

    II. Gruppe 2: Pasienter med avanserte solide svulster som har en BRAF klasse II-mutasjon eller en BRAF-fusjonsmutasjon III. Gruppe 3: Pasienter med kutant melanom som huser en neuroblastom RAS viral onkogen homolog (NRAS) mutasjon IV. Gruppe 4: Pasienter med kutant melanom som har en NRAS-mutasjon som samtykker til parede ferske biopsier, dvs. .

  2. Pasienter i fase 1b gruppe 1: Pasienter må ha mottatt siste dose av tidligere BRAF- og/eller MEK-hemmerbehandling innen 90 dager etter oppstart av BGB-3245 studiebehandling (syklus 1 dag 1)
  3. Deltakerne må gi arkivert tumorvev eller godta en ny tumorbiopsi for mutasjons- og biomarkøranalyse (ferske tumorbiopsier

Nøkkelekskluderingskriterier:

  1. Deltakere som mottar kreftbehandling (kjemoterapi eller andre systemiske kreftbehandlinger, immunterapi, strålebehandling eller kirurgi) på tidspunktet for syklus 1 dag 1.

  2. Alle deltakere som har mottatt tidligere systemisk antikreftbehandling innen følgende tidsrammer vil bli ekskludert:

    1. Systemisk kjemoterapi innen en tidsperiode som er kortere enn sykluslengden som ble brukt for den behandlingen (dvs. 6 uker for nitrosourea, mitomycin C) før syklus 1 dag 1; og
    2. Biologisk terapi (dvs. antistoffer), kontinuerlige eller intermitterende småmolekylære terapier eller andre undersøkelsesmidler innen en periode på 5 ganger halveringstiden til midlet eller ≤4 uker (det som er kortest) før syklus 1 dag 1.
  3. Anamnese eller tilstedeværelse av gastrointestinal sykdom eller annen tilstand som er kjent for å forstyrre absorpsjon, distribusjon, metabolisme eller utskillelse av legemidler.
  4. Aktuelle bevis på symptomatiske CNS-metastaser, leptomeningeal karsinomatose eller ubehandlet ryggmargskompresjon. Asymptomatisk behandlede eller asymptomatiske ubehandlede hjernemetastaser er tillatt så lenge pasientene er klinisk stabile.
  5. Enhver ustabil, eksisterende alvorlig medisinsk tilstand som etter etterforskerens mening kontraindiserer bruken av et studiemedikament, inkludert kjent humant immunsviktvirus (HIV) eller aktivt hepatitt B-virus (HBV) eller hepatitt C-virus (HCV) infeksjon.

MERK: Andre protokolldefinerte inkluderings-/eksklusjonskriterier kan gjelde.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Sekvensiell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Phase 1a: Brimarafenib 5 mg
Participants received brimarafenib 5 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Legemiddel: Brimarafenib
administered orally (PO) once daily at doses specified in the description of each arm
Andre navn:
  • BGB-3245
Eksperimentell: Phase 1a: Brimarafenib 10 mg
Participants received brimarafenib 10 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Legemiddel: Brimarafenib
administered orally (PO) once daily at doses specified in the description of each arm
Andre navn:
  • BGB-3245
Eksperimentell: Phase 1a: Brimarafenib 15 mg
Participants received brimarafenib 15 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Legemiddel: Brimarafenib
administered orally (PO) once daily at doses specified in the description of each arm
Andre navn:
  • BGB-3245
Eksperimentell: Phase 1a: Brimarafenib 25 mg
Participants received brimarafenib 25 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Legemiddel: Brimarafenib
administered orally (PO) once daily at doses specified in the description of each arm
Andre navn:
  • BGB-3245
Eksperimentell: Phase 1a: Brimarafenib 40 mg
Participants received brimarafenib 40 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Legemiddel: Brimarafenib
administered orally (PO) once daily at doses specified in the description of each arm
Andre navn:
  • BGB-3245
Eksperimentell: Phase 1a: Brimarafenib 60 mg
Participants received brimarafenib 60 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Legemiddel: Brimarafenib
administered orally (PO) once daily at doses specified in the description of each arm
Andre navn:
  • BGB-3245
Eksperimentell: Phase 1b: Group 1 (Brimarafenib 25 mg)
Participants with solid tumors harboring B-Raf Proto-Oncogene, Serine/Threonine Kinase (BRAF) V600 mutations (excluding colorectal cancer [CRC]) who had progressed on prior BRAF and/or MEK (mitogen-activated protein kinase) inhibition were randomized to receive 25 mg of brimarafenib once daily. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Legemiddel: Brimarafenib
administered orally (PO) once daily at doses specified in the description of each arm
Andre navn:
  • BGB-3245
Eksperimentell: Phase 1b: Group 1 (Brimarafenib 40 mg Randomized)
Participants with solid tumors harboring BRAF V600 mutations (excluding CRC) who had progressed on prior BRAF and/or MEK inhibition were randomized to receive 40 mg of brimarafenib once daily. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Legemiddel: Brimarafenib
administered orally (PO) once daily at doses specified in the description of each arm
Andre navn:
  • BGB-3245
Eksperimentell: Phase 1b: Group 1 (Brimarafenib 40 mg Non-Randomized)
Participants with solid tumors harboring BRAF V600 mutations (excluding CRC) enrolled under Protocol Version 4.0 were treated with 40 mg of brimarafenib once daily without randomization. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Legemiddel: Brimarafenib
administered orally (PO) once daily at doses specified in the description of each arm
Andre navn:
  • BGB-3245
Eksperimentell: Phase 1b: Group 2 (Brimarafenib 40 mg)
Participants with advanced solid tumors harboring BRAF Class II mutations or a BRAF fusion mutation were treated with 40 mg of brimarafenib once daily. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Legemiddel: Brimarafenib
administered orally (PO) once daily at doses specified in the description of each arm
Andre navn:
  • BGB-3245

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Phase 1a: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Tidsramme: From first dose up to 30 days after the last dose of study treatment. Maximum treatment duration was 47 months.
SAEs were defined as adverse events that resulted in death, were life-threatening, required or prolonged hospitalization, caused significant disability, or were considered important medical events.
From first dose up to 30 days after the last dose of study treatment. Maximum treatment duration was 47 months.
Phase 1a: Maximum Tolerated Dose (MTD) of Brimarafenib
Tidsramme: From first dose through the end of Cycle 1 (approximately 30 days)
The MTD was determined by the Safety Monitoring Committee (SMC) based on the occurrence of dose-limiting toxicities (DLTs), overall safety, and tolerability. The MTD reflects the dose associated with an acceptable level of toxicity (30%).
From first dose through the end of Cycle 1 (approximately 30 days)
Phase 1b: Recommended Phase 2 Dose (RP2D) Confirmation
Tidsramme: From first dose of study drug through last dose (maximum treatment duration in Phase 1b was 25 months)
The optimal RP2D was to be determined based on safety, tolerability, efficacy, and pharmacokinetic (PK) data obtained from participants treated with the two dose levels tested in Phase 1b (25 mg and 40 mg). The RP2D could not be determined since the study was terminated early.
From first dose of study drug through last dose (maximum treatment duration in Phase 1b was 25 months)
Phase 1b: Objective Response Rate (ORR)
Tidsramme: From first dose until disease progression or death, Maximum treatment duration was 25 months.
ORR was defined as the percentage of participants who achieved a best overall response of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
From first dose until disease progression or death, Maximum treatment duration was 25 months.

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Phase 1a: ORR
Tidsramme: From first dose until disease progression or death, Maximum treatment duration was 47 months.
ORR was defined as the percentage of participants who achieved a best overall response of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
From first dose until disease progression or death, Maximum treatment duration was 47 months.
Duration of Response (DOR)
Tidsramme: From first dose until disease progression or death, Maximum treatment duration was 47 months in Phase 1a and 25 months in Phase 1b.
DOR was defined as the time from the date that a confirmed response (CR or PR) was first observed per RECIST 1.1 to the date of first documented disease progression or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method.
From first dose until disease progression or death, Maximum treatment duration was 47 months in Phase 1a and 25 months in Phase 1b.
Clinical Benefit Rate (CBR)
Tidsramme: From first dose until disease progression or death, Maximum treatment duration was 47 months.
CBR is defined as the percentage of participants with confirmed CR, PR, or durable stable disease (stable disease ≥ 24 weeks).
From first dose until disease progression or death, Maximum treatment duration was 47 months.
Progression-free Survival (PFS)
Tidsramme: From first dose until disease progression or death, Maximum treatment duration was 47 months Phase 1a and 25 months in Phase 1b.
PFS was defined as the time from randomization to the date of first documented disease progression per RECIST v1.1 or death from any cause, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method.
From first dose until disease progression or death, Maximum treatment duration was 47 months Phase 1a and 25 months in Phase 1b.
Duration of Stable Disease (DSD)
Tidsramme: From first dose until disease progression or death, Maximum treatment duration was 47 months Phase 1a and 25 months in Phase 1b.
DSD is defined as the time interval, in the absence of either confirmed CR or PR, between the date of the first administration of study drug and the first documented disease progression per RECIST v1.1 or death due to any cause, whichever occurred first.
From first dose until disease progression or death, Maximum treatment duration was 47 months Phase 1a and 25 months in Phase 1b.
Phase 1b: Disease Control Rate (DCR)
Tidsramme: From first dose until death, maximum treatment duration was 25 months.
DCR is defined as the percentage of participants with a best overall response of CR, PR, or SD per RECIST v1.1 criteria. DCR reflects the percentage of participants whose disease did not progress during the study, including those with confirmed responses and those with durable SD.
From first dose until death, maximum treatment duration was 25 months.
Phase 1b: Overall Survival (OS)
Tidsramme: From first dose until death, assessed maximum treatment duration was 25 months.
OS was defined as the time from randomization to the date of death from any cause. Median OS was estimated using the Kaplan-Meier method.
From first dose until death, assessed maximum treatment duration was 25 months.
Phase 1a: Trough Plasma Concentration (Ctrough) of Brimarafenib
Tidsramme: Predose on Cycle 1 Day 15; Cycle 2 Day 1, Cycle 3 Day 1, and Cycle 4 Day 1. Each cycle was 28 days.
Ctrough is the observed concentration at predose.
Predose on Cycle 1 Day 15; Cycle 2 Day 1, Cycle 3 Day 1, and Cycle 4 Day 1. Each cycle was 28 days.
Phase 1a: Area Under the Concentration-time Curve From Dosing to Time of Last Quantifiable Concentration (AUClast) of Brimarafenib
Tidsramme: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose); Cycle 1 Days 2, 3, 4, 8, and 15; Cycle 2 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose)
Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose); Cycle 1 Days 2, 3, 4, 8, and 15; Cycle 2 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose)
Phase 1a: Area Under the Concentration-time Curve From Dosing Time to Time Tau (Tau=24 Hours) of Brimarafenib
Tidsramme: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, and 24 hours postdose)
Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, and 24 hours postdose)
Phase 1a: Area Under the Concentration-time Curve From Dosing Extrapolated to Infinity (AUC0-inf) of Brimarafenib
Tidsramme: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Phase 1a: Maximum Observed Plasma Concentration (Cmax) of Brimarafenib
Tidsramme: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose); Cycle 2 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose)
Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose); Cycle 2 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose)
Phase 1a: Time to Maximum Observed Plasma Concentration (Tmax) of Brimarafenib
Tidsramme: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, a 8, 24, 48, and 72 hours postdose); Cycle 2 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose)
Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, a 8, 24, 48, and 72 hours postdose); Cycle 2 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose)
Phase 1a: Elimination Half-Life (t½) of Brimarafenib
Tidsramme: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Phase 1a: Apparent Oral Clearance (CL/F) of Brimarafenib
Tidsramme: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Phase 1a: Apparent Oral Volume of Distribution (Vz/F) of Brimarafenib
Tidsramme: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Phase 1b: Plasma Concentrations for Brimarafenib
Tidsramme: C1D1 (predose, 1, 3h postdose); C1D3, D8, D22 (±2d; predose, 2-4h postdose on D22); C2D1 (predose, 1, 3h); C3, 4, 6, 8, 10, 12 D1 and every 3rd cycle (predose); and at treatment discontinuation (2-4h).
C1D1 (predose, 1, 3h postdose); C1D3, D8, D22 (±2d; predose, 2-4h postdose on D22); C2D1 (predose, 1, 3h); C3, 4, 6, 8, 10, 12 D1 and every 3rd cycle (predose); and at treatment discontinuation (2-4h).
Phase 1b: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Tidsramme: From first dose until 30 days after last dose of study treatment. Maximum treatment duration was 25 months.
SAEs were defined as events that resulted in death, were life-threatening, required or prolonged hospitalization, caused significant disability, or were considered important medical events.
From first dose until 30 days after last dose of study treatment. Maximum treatment duration was 25 months.

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

MapKure, LLC

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

  • Alison M. Schram, Vivek Subbiah, Ryan Sullivan, Rasha Cosman, Jia Liu, Eric I. Sbar, Thuy Hoang, Jiarong Chen, Mark Johnson, Vincent Amoruccio, Todd Shearer, Adeela Kamal, Jocelyn Lewis, Wenlin Shao, Badreddin Edris, Lusong Luo, Jayesh Desai; Abstract CT031: A first-in-human, phase 1a/1b, open-label, dose-escalation and expansion study to investigate the safety, pharmacokinetics, and antitumor activity of the RAF dimer inhibitor BGB-3245 in patients with advanced or refractory tumors. Cancer Res 15 April 2023; 83 (8_Supplement): CT031. https://doi.org/10.1158/1538-7445.AM2023-CT031

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

10. februar 2020

Primær fullføring (Faktiske)

8. august 2025

Studiet fullført (Faktiske)

8. august 2025

Datoer for studieregistrering

Først innsendt

21. januar 2020

Først innsendt som oppfylte QC-kriteriene

29. januar 2020

Først lagt ut (Faktiske)

31. januar 2020

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

31. august 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

6. juli 2026

Sist bekreftet

1. april 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • BGB-3245-AU-001

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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