Sikkerhet og effekt av terapier for metastatisk kastrasjonsresistent prostatakreft (mCRPC)
4. august 2026 oppdatert av: Amgen
En hovedprotokoll som evaluerer sikkerheten og effektiviteten til terapier for metastatisk kastrasjonsresistent prostatakreft (mCRPC)
Dette er en hovedprotokoll utviklet for å evaluere sikkerheten og effekten av undersøkelsesterapier hos deltakere med metastatisk kastrasjonsresistent prostatakreft (mCRPC).
Studieoversikt
Status
Avsluttet
Intervensjon / Behandling
Detaljert beskrivelse
Dette er en hovedprotokoll utviklet for å evaluere sikkerhet, tolerabilitet og maksimal tolerert dose (MTD) eller anbefalt fase 2-dose (RP2D) og effekt av Acapatamab, i kombinasjon med enzalutamid, abirateron eller PD1-hemmeren AMG 404, AMG 404 monoterapi , samt Acapatamab monoterapi, hos deltakere med metastatisk kastrasjonsresistent prostatakreft (mCRPC).
Studietype
Intervensjonell
Registrering (Faktiske)
55
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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New South Wales
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Darlinghurst, New South Wales, Australia, 2010
- St Vincents Hospital Sydney
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København Ø, Danmark, 2100
- Rigshospitalet
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Alabama
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Birmingham, Alabama, Forente stater, 35294
- University of Alabama at Birmingham
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California
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Orange, California, Forente stater, 92868
- University of California at Irvine Medical Center
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San Francisco, California, Forente stater, 94158
- University of California San Francisco Mission Bay Campus
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Illinois
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Chicago, Illinois, Forente stater, 60637
- University of Chicago
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Kentucky
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Louisville, Kentucky, Forente stater, 40207
- Norton Cancer Institute
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Texas
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Dallas, Texas, Forente stater, 75390
- University of Texas Southwestern Medical Center
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Houston, Texas, Forente stater, 77030
- University of Texas MD Anderson Cancer Center
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Navarre
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Pamplona, Navarre, Spania, 31008
- Clinica Universidad de Navarra
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Sutton, Storbritannia, SM2 5PT
- Royal Marsden Hospital
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Lund, Sverige, 221 85
- Skånes universitetssjukhus
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Stockholm, Sverige, 171 76
- Karolinska Universitetssjukhuset Solna
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Uppsala, Sverige, 75185
- Akademiska Sjukhuset
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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 til 99 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Beskrivelse
Alle deler
Inklusjonskriterier:
- ≥ 18 år (eller lovlig voksen alder i landet)
- Forsøkspersonen har gitt informert samtykke før oppstart av studiespesifikke aktiviteter/prosedyrer
- Personer med mCRPC med histologisk eller cytologisk bekreftet adenokarsinom i prostata
- Forsøkspersonene bør ha gjennomgått bilateral orkiektomi eller bør være på kontinuerlig behandling med androgen deprivasjon med en gonadotropinfrigjørende hormonagonist eller -antagonist (testosteron ≤ 50 ng/dL (eller 1,7 nmol/L))
Ekskluderingskriterier:
- Metastaser i sentralnervesystemet (CNS) eller leptomeningeal sykdom
- Anamnese eller tilstedeværelse av klinisk relevant CNS-patologi
- Bekreftet anamnese eller nåværende autoimmun sykdom eller andre sykdommer som krever permanent immunsuppressiv behandling
- Hjerteinfarkt, ukontrollert hypertensjon, ustabil angina, hjertearytmi som krever medisinering og/eller symptomatisk kongestiv hjertesvikt (New York Heart Association > klasse II) innen 12 måneder
- Tidligere behandling med en taxan for mCRPC
- Større operasjon og/eller stråling innen 4 uker
Anamnese eller bevis på alvorlig akutt respiratorisk syndrom coronavirus 2 (SARS-CoV-2) infeksjon med mindre det er avtalt med medisinsk monitor og oppfyller følgende kriterier:
- Negativ test for SARS-CoV-2 RNA ved sanntids polymerasekjedereaksjon (RT-PCR) innen 72 timer etter første dose av Acapatamab (eller AMG 404 i del 3)
- Ingen akutte symptomer på COVID-19-sykdom innen 10 dager før første dose av Acapatamab (eller AMG 404 i del 3) (regnet fra dagen med positiv test for asymptomatiske personer)
Tidligere/samtidig klinisk studieerfaring
- Mottar for øyeblikket behandling i en annen undersøkelsesenhet eller medikamentstudie, eller mindre enn 4 uker siden avsluttet behandling på en annen undersøkelsesenhet eller medikamentstudie(r). Andre undersøkelsesprosedyrer mens du deltar i denne studien er ekskludert med unntak av undersøkelsesskanninger.
Kun underprotokoll A:
Inklusjonskriterier
• Personer som planlegger å få enzalutamid for første gang for mCRPC
Eksklusjonskriterier
- Bruk av sterke CYP2C8-hemmere eller sterke CYP3A4-induktorer
- Bruk av legemidler med smal terapeutisk indeks som er substrater for CYP3A4, CYP2C9 eller CYP2C19
Kun underprotokoll B:
Inklusjonskriterier
- Personer som planlegger å motta abirateron for første gang for mCRPC-eksklusjonskriterier
- Baseline moderat og alvorlig nedsatt leverfunksjon (Child-Pugh klasse B og C)
- Tilstedeværelse av ukontrollert hypertensjon, hypokalemi eller væskeretensjon
- Anamnese eller tilstedeværelse av binyrebarksvikt
- Bruk av samtidig medisiner som er sensitive substrater for CYP2D6 med en smal terapeutisk indeks
- Bruk av sterke CYP3A4-induktorer
Kun underprotokoll C:
Inklusjonskriterier
- Personer som er refraktære mot en ny antiandrogen terapi. Forsøkspersonene må ikke være kvalifisert for eller nekte taksanbehandling.
- Bevis på progressiv sykdom, definert som 1 eller flere PCWG3-kriterier: PSA-nivå >/=1 ng/mL som har økt ved minst 2 påfølgende anledninger med minst 1 ukes mellomrom, nodal eller visceral progresjon som definert av RECIST 1.1 med PCGW3-modifikasjoner, og/eller utseende av 2 eller flere nye lesjoner i benskanning Eksklusjonskriterier
- Anamnese eller bevis på interstitiell lungesykdom eller aktiv, ikke-infeksiøs pneumonitt
- Personer på en tidligere PD-1- eller PD-L1-hemmer som opplevde en grad 3 eller høyere immunrelatert bivirkning før første dosedag
Kun underprotokoll D:
Inklusjonskriterier
- Forsøkspersonene kan ha hatt nye hormonelle terapier (NHT; f.eks. abirateron, enzalutamid, apalutamid eller darolutamid) for prostatakreft, men ikke mer enn 1 NHT for metastatisk prostatakreft
- Ikke kvalifisert for eller avslå taksanbehandling
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: Randomisert
- Intervensjonsmodell: Sekvensiell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: Acapatamab og Enzalutamid: Doseundersøkelse
Doseutforskningsdelen av studien vil estimere MTD/anbefalt fase 2-dose (RP2D) av Acapatamab i kombinasjon med enzalutamid.
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Acapatamab vil bli administrert som en intravenøs (IV) infusjon.
Andre navn:
Enzalutamid vil bli administrert oralt.
Andre navn:
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Eksperimentell: Acapatamab og Enzalutamid: Doseutvidelse
Etter doseutforskning vil doseutvidelse utføres for å bekrefte sikkerheten og toleransen til den valgte dosen og for ytterligere å evaluere effekten av Acapatamab i kombinasjon med enzalutamid.
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Acapatamab vil bli administrert som en intravenøs (IV) infusjon.
Andre navn:
Enzalutamid vil bli administrert oralt.
Andre navn:
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Eksperimentell: Acapatamab og Abiraterone: Doseundersøkelse
Doseutforskningsdelen av studien vil estimere MTD/anbefalt fase 2-dose (RP2D) av Acapatamab i kombinasjon med abirateron.
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Acapatamab vil bli administrert som en intravenøs (IV) infusjon.
Andre navn:
Abirateron vil bli administrert oralt.
Andre navn:
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Eksperimentell: Acapatamab og Abiraterone: Doseutvidelse
Etter doseutforskning vil doseutvidelse utføres for å bekrefte sikkerheten og toleransen til den valgte dosen og for ytterligere å evaluere effekten av Acapatamab i kombinasjon med abirateron.
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Acapatamab vil bli administrert som en intravenøs (IV) infusjon.
Andre navn:
Abirateron vil bli administrert oralt.
Andre navn:
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Eksperimentell: Acapatamab og AMG 404: Doseundersøkelse
Doseutforskningsdelen av studien vil estimere MTD/RP2D for Acapatamab i kombinasjon med AMG 404.
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Acapatamab vil bli administrert som en intravenøs (IV) infusjon.
Andre navn:
AMG 404 vil bli administrert som en intravenøs (IV) infusjon.
Andre navn:
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Eksperimentell: Acapatamab og AMG 404: Doseutvidelse
Etter doseutforskning vil doseutvidelse utføres for å bekrefte sikkerheten og toleransen til den valgte dosen og for å ytterligere evaluere effekten av Acapatamab i kombinasjon med AMG 404.
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Acapatamab vil bli administrert som en intravenøs (IV) infusjon.
Andre navn:
AMG 404 vil bli administrert som en intravenøs (IV) infusjon.
Andre navn:
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Aktiv komparator: AMG 404 monoterapi
AMG 404 monoterapi blir utført for å evaluere den foreløpige antitumoraktiviteten til PD-1-hemming i mCRPC-populasjonen.
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AMG 404 vil bli administrert som en intravenøs (IV) infusjon.
Andre navn:
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Eksperimentell: Acapatamab og Enzalutamid: Doseutvidelse Asia-kohort
Etter doseutforskning vil doseutvidelse utføres i Asia-kohorten ved kombinasjonen MTD/RP2D bestemt i doseutforskning for å bekrefte sikkerheten, toleransen og PK av Acapatamab i kombinasjon med enzalutamid for forsøkspersoner i Asia.
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Acapatamab vil bli administrert som en intravenøs (IV) infusjon.
Andre navn:
Enzalutamid vil bli administrert oralt.
Andre navn:
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Eksperimentell: Acapatamab og Abiraterone: Doseutvidelse Asia-kohort
Etter doseutforskning vil doseutvidelse bli utført i Asia-kohorten ved kombinasjonen MTD/RP2D bestemt i doseutforskning for å bekrefte sikkerheten, tolerabiliteten og PK av Acapatamab i kombinasjon med abirateron for forsøkspersoner i Asia.
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Acapatamab vil bli administrert som en intravenøs (IV) infusjon.
Andre navn:
Abirateron vil bli administrert oralt.
Andre navn:
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Eksperimentell: Acapatamab og AMG 404: Doseutvidelse Asia-kohort
Etter doseutforskning vil doseutvidelse bli utført i Asia-kohorten ved kombinasjonen MTD/RP2D bestemt i doseutforskning for å bekrefte sikkerheten, toleransen og PK av Acapatamab i kombinasjon med AMG 404 for forsøkspersoner i Asia.
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Acapatamab vil bli administrert som en intravenøs (IV) infusjon.
Andre navn:
AMG 404 vil bli administrert som en intravenøs (IV) infusjon.
Andre navn:
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Eksperimentell: Acapatamab monoterapi
Acapatamab monoterapi blir utført for å evaluere sikkerhet, tolerabilitet, farmakokinetikk (PK), farmakodynamikk og effekt av Acapatamab hos personer med mCRPC.
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Acapatamab vil bli administrert som en intravenøs (IV) infusjon.
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
Tidsramme: Cycle 1: Day 1 to Day 28 (28-day cycle)
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DLTs were defined as any adverse event (AE) (per Common Terminology Criteria for Adverse Events (CTCAE) v5: Grade 5=Death, Grade 4=Life-threatening, Grade 3=Moderate) occurring within 28 days of the first AMG 160 dose, possibly related to the treatment, including:
The complete list of DLTs are described in the protocol |
Cycle 1: Day 1 to Day 28 (28-day cycle)
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Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and Treatment-related AEs
Tidsramme: From first dose of acapatamab/AMG 404 to the first of 30 days after last dose of acapatamab/AMG404, end of trial date or the initiation of a new anticancer therapy; median (min, max) duration was 4.665 (0.33, 25.17) months
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A TEAE was defined as any untoward medical occurrence in a clinical trial participant irrespective of a causal relationship with the trial treatment that started on or after first dose of investigational product (AMG 160 or AMG 404 for Part 1 and 2; AMG 404 for Part 3). A treatment-related TEAE was defined as a TEAE that had a reasonable possibility of being caused by acapatamab, or AMG 404 (subprotocol C, parts 1 and 2 only). Clinically significant changes from baseline in vital signs and clinical laboratory tests were also recorded as TEAEs. |
From first dose of acapatamab/AMG 404 to the first of 30 days after last dose of acapatamab/AMG404, end of trial date or the initiation of a new anticancer therapy; median (min, max) duration was 4.665 (0.33, 25.17) months
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Subprotocol D: Number of Participants Who Experienced TEAEs and Treatment-related AEs
Tidsramme: From first dose of acapatamab to the first of 30 days after last dose of acapatamab, end of trial date or the initiation of a new anticancer therapy, whichever is earlier; median (min, max) duration was 4.665 (0.33, 25.17) months
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A TEAE was defined as any untoward medical occurrence in a clinical trial participant irrespective of a causal relationship with the trial treatment that started after the first dose of acapatamab. A treatment-related TEAE was defined as a TEAE that had a reasonable possibility of being caused by acapatamab. Clinically significant changes from baseline in vital signs and clinical laboratory tests were also recorded as TEAEs. |
From first dose of acapatamab to the first of 30 days after last dose of acapatamab, end of trial date or the initiation of a new anticancer therapy, whichever is earlier; median (min, max) duration was 4.665 (0.33, 25.17) months
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Subprotocol C, Part 3: Objective Response Rate (ORR)
Tidsramme: From Cycle 1 Day 1 until progression, start of new anticancer therapy, or end of trial median (min, max) duration was 6.14 (0.14, 105.14) weeks
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Objective Response is defined as a complete response (CR) or partial response (PR) per RECIST 1.1, confirmed by a repeat assessment at least 4 weeks later.
Participants who did not experience a confirmed CR or PR, or did not have any follow-up tumor assessments were regarded as non-responders.
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From Cycle 1 Day 1 until progression, start of new anticancer therapy, or end of trial median (min, max) duration was 6.14 (0.14, 105.14) weeks
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Subprotocol C, Part 3: Percentage of Participants Who Experienced a Circulating Tumor Cell 0 (CTC0) Response
Tidsramme: Cycle 1 Day 1 to 14 days post-last dose of AMG 404 (each cycle was 28 days, maximum duration of AMG 404 treatment was 105.1 weeks)
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CTC0 response was defined as CTC0 (reduction of CTCs > 0 to 0 at any post-baseline measurement).
The baseline was defined as the last non-missing value on or prior to the pre-dose of AMG 404 assessments on Cycle 1 Day 1.
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Cycle 1 Day 1 to 14 days post-last dose of AMG 404 (each cycle was 28 days, maximum duration of AMG 404 treatment was 105.1 weeks)
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Subprotocol C, Part 3: Percentage of Participants Who Experienced a CTC Conversion Response
Tidsramme: Cycle 1 Day 1 to 14 days post-last dose of AMG 404 (each cycle was 28 days, maximum duration of AMG 404 treatment was 105.1 weeks)
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CTC conversion response was defined as ≥ 5 CTCs/7.5 mL blood at baseline that converted to ≤ 4 CTCs/7.5 mL blood at any post-baseline measurement.
The baseline was defined as the last non-missing value on or prior to the pre-dose assessments of AMG 404 on Cycle 1 Day 1.
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Cycle 1 Day 1 to 14 days post-last dose of AMG 404 (each cycle was 28 days, maximum duration of AMG 404 treatment was 105.1 weeks)
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Subprotocol C, Part 3: Percentage of Participants Who Experienced a Prostate Specific Antigen (PSA) Response
Tidsramme: Cycle 1 Day 1 to 5 months post-last dose of AMG 404 (each cycle was 28 days, maximum duration of AMG 404 treatment was 105.1 weeks)
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A PSA response was defined as the below and must have been confirmed by a second consecutive value 3 weeks later:
The baseline was defined as the last non-missing value on or prior to the pre-dose of AMG 404 assessments on Cycle 1 Day 1. |
Cycle 1 Day 1 to 5 months post-last dose of AMG 404 (each cycle was 28 days, maximum duration of AMG 404 treatment was 105.1 weeks)
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Subprotocols A. B, C (Parts 1 and 2) and D: ORR
Tidsramme: From Cycle 1 Day 1 until progression, start of new anticancer therapy, or until end of trial (each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Objective Response is defined as a CR or PR per RECIST 1.1, confirmed by a repeat assessment at least 4 weeks later.
Participants who did not experience a confirmed CR or PR, or did not have any follow-up tumor assessments were regarded as non-responders.
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From Cycle 1 Day 1 until progression, start of new anticancer therapy, or until end of trial (each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Subprotocols A, B, C (Parts 1 and 2) and D: Percentage of Participants Who Experienced a CTC0 Response
Tidsramme: From Cycle 1 Day 1 until progression, start of new anticancer therapy, or until end of trial (each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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CTC0 response was defined as CTC0 (reduction of CTCs > 0 to 0 at any post-baseline measurement).
The baseline was defined as the last non-missing value on or prior to the pre-dose of acapatamab assessments on Cycle 1 Day 1 > 0.
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From Cycle 1 Day 1 until progression, start of new anticancer therapy, or until end of trial (each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Subprotocols A, B, C (Parts 1 and 2) and D: Percentage of Participants Who Experienced a CTC Conversion Response
Tidsramme: From Cycle 1 Day 1 until progression, start of new anticancer therapy, or until end of trial (each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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CTC conversion response was defined as ≥ 5 CTCs/7.5 mL blood at baseline that converted to ≤ 4 CTCs/7.5 mL blood at any post-baseline measurement.
The baseline was defined as the last non-missing value on or prior to the pre-dose of acapatamab assessments on Cycle 1 Day 1.
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From Cycle 1 Day 1 until progression, start of new anticancer therapy, or until end of trial (each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Subprotocols A, B, C (Parts 1 and 2) and D: Percentage of Participants Who Experienced a PSA Response
Tidsramme: Cycle 1 Day 1 to 5 months post-last dose of acapatamab/AMG 404 (each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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A PSA response was defined as the below and must have been confirmed by a second consecutive value 3 weeks later:
The baseline was defined as the last non-missing value on or prior to the pre-dose of acapatamab assessments on Cycle 1 Day 1. |
Cycle 1 Day 1 to 5 months post-last dose of acapatamab/AMG 404 (each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Duration of CTC0 Response
Tidsramme: From date of initial CTC0 response to the earlier of CTC0 progression or death (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Duration of CTC0 response was defined as the time from the date of initial CTC0 response to the earlier of CTC0 progression or death.
Participants who had not ended their response at the time of analysis had duration of CTC0 response censored on the date of their last CTC0 or CTC conversion assessment.
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From date of initial CTC0 response to the earlier of CTC0 progression or death (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Duration of CTC Conversion Response
Tidsramme: From the date of an initial CTC conversion response to the earlier of CTC conversion progression or death (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Duration of CTC conversion response was defined as the time from the date of an initial CTC conversion response to the earlier of CTC conversion progression or death.
Participants who had not ended their response at the time of analysis had duration of CTC response censored on the date of their last CTC0 or CTC conversion assessment.
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From the date of an initial CTC conversion response to the earlier of CTC conversion progression or death (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Duration of PSA Response
Tidsramme: From date of an initial PSA response (PSA 50) to the earlier of PSA progression or death (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Duration of PSA response was defined as the time of an initial PSA response (PSA 50) to the earlier of PSA progression or death.
Participants who had not ended their response at the time of analysis had duration of PSA response censored on the date of their last PSA measurement.
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From date of an initial PSA response (PSA 50) to the earlier of PSA progression or death (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Duration of Response Per RECIST 1.1
Tidsramme: From date of an initial objective response per RECIST 1.1 to the earlier of soft-tissue progression per RECIST 1.1 or death (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Duration of response per RECIST 1.1 was defined as the time from the date of an initial objective response (CR/PR) per RECIST 1.1 to the earlier of soft-tissue progression per RECIST 1.1 or death.
CR/PR must have been confirmed at least 4 weeks later.
Participants who had not ended their response at the time of analysis had duration of response censored at their last evaluable tumor assessment by computed tomography (CT)/magnetic resonance imaging (MRI) scan.
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From date of an initial objective response per RECIST 1.1 to the earlier of soft-tissue progression per RECIST 1.1 or death (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Overall Survival (OS)
Tidsramme: From the date of study Day 1 until death due to any cause (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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OS was defined as the time from the date of trial Day 1 until death due to any cause.
OS time (months) = (date of death - trial Day 1 + 1) x 12/365.25.
Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was alive.
The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Kalbfleisch and Prentice.
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From the date of study Day 1 until death due to any cause (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Radiographic Progression Free Survival (rPFS)
Tidsramme: From trial Day 1 to the earlier of a radiographic progression or death from any cause (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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rPFS was defined as the time from trial Day 1 to radiographic progression.
If a participant had no evaluable post-baseline and on-trial disease assessment and was on trial without disease progression (PD) or death recorded, rPFS was censored on the date of the first dose of the investigational product (IP).
rPFS was censored at the last evaluable radiographic tumor assessment date for participants who had no PD, death or new anti-cancer therapy reported, started a new anti-cancer therapy prior to PD or death, if death recorded without new anti-cancer therapy and without PD, if death or PD immediately after more than one consecutively missed tumor assessment occurred.
The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley.
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From trial Day 1 to the earlier of a radiographic progression or death from any cause (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: PSA PFS
Tidsramme: From trial Day 1 to the earlier of a PSA progression or death from any cause (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
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PSA PFS was defined as the interval from trial Day 1 to the earlier of a PSA progression or death from any cause; otherwise, PSA PFS was censored on the date of the last PSA measurement.
If a participant had no baseline or post-baseline PSA measurement and a vital status of alive or known, PSA PFS was censored at trial Day 1.
The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley.
|
From trial Day 1 to the earlier of a PSA progression or death from any cause (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
|
|
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Clinical PFS
Tidsramme: From first dose of acapatamab or AMG 404 (subprotocol C only) to clinical disease progression or death from any cause (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
|
Clinical PFS was defined as the time from the first dose to clinical disease progression or death from any cause.
If a participant had no evaluable post-baseline or on-trial disease assessment or was on trial without PD or death recorded, clinical PFS was censored on the date of the first dose of the IP.
Otherwise, clinical PFS was censored on the date of last assessment.
The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley.
|
From first dose of acapatamab or AMG 404 (subprotocol C only) to clinical disease progression or death from any cause (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
|
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Time to Radiographic Progression
Tidsramme: From trial Day 1 to radiographic progression in the absence of subsequent anticancer therapy (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
|
Time to radiographic progression was defined as the interval from Day 1 to radiographic progression in the absence of subsequent anticancer therapy. If a participant had no evaluable post-baseline and on-trial disease assessment and was on trial without PD or death recorded, time to radiographic progression was censored on the date of the first dose of the IP. Time to radiographic progression was censored on the date of last evaluable radiographic tumor assessment for participants who:
The median was estimated using the Kaplan-Meier method and the 95% CI was estimated using the method by Brookmeyer and Crowley. |
From trial Day 1 to radiographic progression in the absence of subsequent anticancer therapy (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
|
|
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Time to PSA Progression
Tidsramme: From trial Day 1 to PSA progression (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
|
Time to PSA progression was defined as the interval from trial Day 1 to PSA progression.
If a participant had no evaluable post-baseline or on-trial PSA assessment, time to PSA progression was censored on the date of the first dose of the IP.
Otherwise, time to PSA progression was censored on the date of the last PSA assessment.
The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley.
|
From trial Day 1 to PSA progression (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
|
|
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Time to Subsequent Therapy
Tidsramme: From trial Day 1 to the time a participant starts/receives the subsequent cancer therapy/subsequent therapy (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
|
Time to subsequent therapy was defined as the interval from trial Day 1 to the time a participant starts/receives the subsequent cancer therapy/subsequent therapy; otherwise, time to subsequent therapy was censored at the last known date of any of the trial assessments prior to initiating the subsequent cancer therapy/subsequent therapy.
The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley.
|
From trial Day 1 to the time a participant starts/receives the subsequent cancer therapy/subsequent therapy (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
|
|
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Percentage of Participants Who Experienced a Gallium Prostate-specific Membrane Antigen-11 (PSMA-11) Response
Tidsramme: Cycle 1 Day 1 to 14 days post-last dose of acapatamab or AMG 404 (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
|
A Gallium PSMA-11 response was defined as a ≥ 50% reduction from baseline in the maximum standardized update value (SUV) using 68Gallium (68Ga)-PSMA-11 positron emission tomography (PET)/CT.
PSMA-11 response percentages were based on the number of participants with a baseline PSMA assessment (defined as the last non-missing value on or prior to the pre-dose of acapatamab/AMG 404 assessments) on Cycle 1 Day 1.
The 95% confidence interval was calculated based on the Clopper-Pearson method.
|
Cycle 1 Day 1 to 14 days post-last dose of acapatamab or AMG 404 (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
|
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Time to Symptomatic Skeletal Events
Tidsramme: From trial Day 1 to the first symptomatic skeletal event (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
|
Time to symptomatic skeletal events was defined as time from trial Day 1 to the first symptomatic skeletal event, otherwise time to symptomatic skeletal event was censored at the last dose of acapatamab/AMG 404 or end of safety follow-up date, whichever was later.
Symptomatic skeletal events included fracture, spinal cord compression and radiation or surgery to bone.
The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley.
|
From trial Day 1 to the first symptomatic skeletal event (maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.14 weeks)
|
|
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Total Alkaline Phosphatase Levels
Tidsramme: Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.1 weeks).
|
Alkaline phosphatase levels were collected locally and centrally.
|
Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.1 weeks).
|
|
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Bone Specific Alkaline Phosphatase Levels
Tidsramme: Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.1 weeks).
|
Bone specific alkaline phosphatase levels were collected locally and centrally.
|
Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.1 weeks).
|
|
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Lactate Dehydrogenase Levels
Tidsramme: Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.1 weeks).
|
Lactate dehydrogenase levels were collected locally and centrally.
|
Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.1 weeks).
|
|
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Hemoglobin Levels
Tidsramme: Baseline, safety follow-up visit (up to 30 days post-last dose of acapatamab/AMG 404), safety follow-up 2 (subprotocol C only, up to 5 months post-dose). Each cycle = 28 days, max acapatamab duration = 98.43 weeks, max AMG 404 duration = 105.1 weeks.
|
Hemoglobin levels were collected locally.
|
Baseline, safety follow-up visit (up to 30 days post-last dose of acapatamab/AMG 404), safety follow-up 2 (subprotocol C only, up to 5 months post-dose). Each cycle = 28 days, max acapatamab duration = 98.43 weeks, max AMG 404 duration = 105.1 weeks.
|
|
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Neutrophil-to-lymphocyte Ratio
Tidsramme: Baseline, safety follow-up visit (up to 30 days post-last dose of acapatamab/AMG 404), safety follow-up 2 (subprotocol C only, up to 5 months post-dose). Each cycle = 28 days, max acapatamab duration = 98.43 weeks, max AMG 404 duration = 105.1 weeks.
|
Data for the neutrophil-to-lymphocyte ratio were collected locally.
Neutrophil-to-lymphocyte ratio was calculated by dividing the number of absolute neutrophils by the number of lymphocytes.
|
Baseline, safety follow-up visit (up to 30 days post-last dose of acapatamab/AMG 404), safety follow-up 2 (subprotocol C only, up to 5 months post-dose). Each cycle = 28 days, max acapatamab duration = 98.43 weeks, max AMG 404 duration = 105.1 weeks.
|
|
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Urine N-telopeptide Levels
Tidsramme: Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.1 weeks).
|
Urine N-telopeptide levels were collected centrally.
|
Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.43 weeks/AMG 404 treatment was 105.1 weeks).
|
|
Subprotocol A, B and C (Parts 1 and 2) and D: Maximum Serum Concentration (Cmax) of Acapatamab
Tidsramme: Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days)
|
Serum concentrations of acapatamab were determined using a validated assay.
|
Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days)
|
|
Subprotocol A, B and C (Parts 1 and 2) and D: Area Under the Curve Over the Dosing Interval (AUCtau)
Tidsramme: Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days)
|
Serum concentrations of acapatamab were determined using a validated assay.
|
Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days)
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Subprotocol A, B and C (Parts 1 and 2) and D: Time to Reach Cmax (Tmax) of Acapatamab
Tidsramme: Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days)
|
Serum concentrations of acapatamab were determined using a validated assay.
|
Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days)
|
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Subprotocol A, B and C (Parts 1 and 2) and D: Terminal Half-life (t1/2z) of Acapatamab
Tidsramme: Cycle 2: Days 1 to 14 (each cycle was 28 days)
|
Serum concentrations of acapatamab were determined using a validated assay.
|
Cycle 2: Days 1 to 14 (each cycle was 28 days)
|
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Subprotocol C, Part 3: Number of Participants Who Experienced TEAEs and Treatment-related AEs
Tidsramme: From first dose of AMG 404 to the first of 30 days after last dose of acapatamab, end of trial date or the initiation of a new anticancer therapy; median (min, max) duration was 6.14 (0.14, 105.14) weeks
|
A TEAE was defined as any untoward medical occurrence in a clinical trial participant irrespective of a causal relationship with the trial treatment that started after the first dose of acapatamab. A treatment-related TEAE was defined as a TEAE that had a reasonable possibility of being caused by acapatamab. Clinically significant changes from baseline in vital signs and clinical laboratory tests were also recorded as TEAEs. |
From first dose of AMG 404 to the first of 30 days after last dose of acapatamab, end of trial date or the initiation of a new anticancer therapy; median (min, max) duration was 6.14 (0.14, 105.14) weeks
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Studieleder: MD, Amgen
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.
Hjelpsomme linker
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)
15. januar 2021
Primær fullføring (Faktiske)
23. oktober 2023
Studiet fullført (Faktiske)
23. oktober 2023
Datoer for studieregistrering
Først innsendt
13. november 2020
Først innsendt som oppfylte QC-kriteriene
13. november 2020
Først lagt ut (Faktiske)
17. november 2020
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
26. august 2026
Siste oppdatering sendt inn som oppfylte QC-kriteriene
4. august 2026
Sist bekreftet
1. juli 2026
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
- mCRPC
- Acapatamab
- HALF-LIFE UTVIDET (HLE) BITT
- Metastatisk kastrasjonsresistent prostatakreft
- 68
- Gallium (68Ga)-prostataspesifikk membran
- antigen (PSMA)-11 positronemisjon
- tomografi (PET)/computertomografi (CT)
- og
- 18
- F-fluordeoksyglukose (FDG) PET/CT
- basert responsevaluering
- Bispesifikk T-celle-engager
- BITE
Ytterligere relevante MeSH-vilkår
- Sår og skader
- Kjemisk-induserte lidelser
- Forgiftning
- Biter og stikk
- Antineoplastiske midler, immunologiske
- Antineoplastiske midler
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Hormoner, hormonsubstitutter og hormonantagonister
- Hormonantagonister
- Androgenantagonister
- Aminosyrer, peptider og proteiner
- Proteiner
- Farmakologiske handlinger
- Kjemiske handlinger og bruk
- Terapeutisk bruk
- Enzymer
- Enzymer og koenzymer
- Oksidoreduktaser
- Cytokromer
- Blandede funksjoner oksygenaser
- Oksygenaser
- Hemeproteiner
- Immune Checkpoint-hemmere
- Androgenreseptorantagonister
- abirateron
- Enzalutamid
- Cytochrome P-450 enzymsystem
Andre studie-ID-numre
- 20190505
- 2020-001305-23 (EudraCT-nummer)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
JA
IPD-planbeskrivelse
Avidentifiserte individuelle pasientdata for variabler som er nødvendige for å løse det spesifikke forskningsspørsmålet i en godkjent forespørsel om datadeling.
IPD-delingstidsramme
Forespørsler om datadeling knyttet til denne studien vil bli vurdert med start 18 måneder etter at studien er avsluttet og enten 1) produktet og indikasjonen har fått markedsføringstillatelse i både USA og Europa eller 2) klinisk utvikling for produktet og/eller indikasjonen avbrytes og dataene vil ikke bli sendt til regulerende myndigheter.
Det er ingen sluttdato for kvalifisering til å sende inn en forespørsel om datadeling for denne studien.
Tilgangskriterier for IPD-deling
Kvalifiserte forskere kan sende inn en forespørsel som inneholder forskningsmålene, Amgen-produktet(e) og Amgen-studien/studiene i omfang, endepunkter/resultater av interesse, statistisk analyseplan, datakrav, publiseringsplan og kvalifikasjonene til forskeren(e).
Generelt innvilger ikke Amgen eksterne forespørsler om individuelle pasientdata med det formål å revurdere sikkerhets- og effektspørsmål som allerede er behandlet i produktmerkingen.
Forespørsler vurderes av en komité med interne rådgivere.
Hvis den ikke blir godkjent, vil et uavhengig granskningspanel for datadeling dømme og ta den endelige avgjørelsen.
Ved godkjenning vil informasjon som er nødvendig for å løse forskningsspørsmålet, gis i henhold til vilkårene i en datadelingsavtale.
Dette kan inkludere anonymiserte individuelle pasientdata og/eller tilgjengelige støttedokumenter, som inneholder fragmenter av analysekode der det er gitt i analysespesifikasjonene.
Ytterligere detaljer er tilgjengelig på URL-en nedenfor.
IPD-deling Støtteinformasjonstype
- STUDY_PROTOCOL
- SEVJE
- ICF
- CSR
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Ja
Studerer et amerikansk FDA-regulert enhetsprodukt
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. .