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Veiligheid en werkzaamheid van therapieën voor gemetastaseerde castratieresistente prostaatkanker (mCRPC)

4 augustus 2026 bijgewerkt door: Amgen

Een hoofdprotocol ter evaluatie van de veiligheid en werkzaamheid van therapieën voor gemetastaseerde castratieresistente prostaatkanker (mCRPC)

Dit is een hoofdprotocol dat is ontworpen om de veiligheid en werkzaamheid van experimentele therapieën te evalueren bij deelnemers met gemetastaseerde castratieresistente prostaatkanker (mCRPC).

Studie Overzicht

Toestand

Beëindigd

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Dit is een hoofdprotocol dat is ontworpen om de veiligheid, verdraagbaarheid en maximaal getolereerde dosis (MTD) of aanbevolen fase 2-dosis (RP2D) en werkzaamheid van acapatamab, in combinatie met enzalutamide, abiraterone of de PD1-remmer AMG 404, AMG 404 als monotherapie te evalueren , evenals Acapatamab-monotherapie, bij deelnemers met gemetastaseerde castratieresistente prostaatkanker (mCRPC).

Studietype

Ingrijpend

Inschrijving (Werkelijk)

55

Fase

  • Fase 2
  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Australië
    • New South Wales
      • Darlinghurst, New South Wales, Australië, 2010
        • St Vincents Hospital Sydney
  • Denemarken
      • København Ø, Denemarken, 2100
        • Rigshospitalet
  • Spanje
    • Navarre
      • Pamplona, Navarre, Spanje, 31008
        • Clinica Universidad de Navarra
  • Verenigd Koninkrijk
      • Sutton, Verenigd Koninkrijk, SM2 5PT
        • Royal Marsden Hospital
  • Verenigde Staten
    • Alabama
      • Birmingham, Alabama, Verenigde Staten, 35294
        • University of Alabama at Birmingham
    • California
      • Orange, California, Verenigde Staten, 92868
        • University of California at Irvine Medical Center
      • San Francisco, California, Verenigde Staten, 94158
        • University of California San Francisco Mission Bay Campus
    • Illinois
      • Chicago, Illinois, Verenigde Staten, 60637
        • University of Chicago
    • Kentucky
      • Louisville, Kentucky, Verenigde Staten, 40207
        • Norton Cancer Institute
    • Texas
      • Dallas, Texas, Verenigde Staten, 75390
        • University of Texas Southwestern Medical Center
      • Houston, Texas, Verenigde Staten, 77030
        • University of Texas MD Anderson Cancer Center
  • Zweden
      • Lund, Zweden, 221 85
        • Skånes universitetssjukhus
      • Stockholm, Zweden, 171 76
        • Karolinska Universitetssjukhuset Solna
      • Uppsala, Zweden, 75185
        • Akademiska Sjukhuset

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 99 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Beschrijving

Alle delen

Inclusiecriteria:

  • ≥ 18 jaar (of wettelijke volwassen leeftijd in het land)
  • De proefpersoon heeft geïnformeerde toestemming gegeven voorafgaand aan de start van studiespecifieke activiteiten/procedures
  • Proefpersonen met mCRPC met histologisch of cytologisch bevestigd adenocarcinoom van de prostaat
  • Proefpersonen moeten een bilaterale orchidectomie hebben ondergaan of moeten een continue androgeendeprivatietherapie ondergaan met een gonadotropine-releasing hormoon-agonist of -antagonist (testosteron ≤ 50 ng/dl (of 1,7 nmol/l))

Uitsluitingscriteria:

  • Metastasen van het centrale zenuwstelsel (CZS) of leptomeningeale ziekte
  • Geschiedenis of aanwezigheid van klinisch relevante CZS-pathologie
  • Bevestigde geschiedenis of huidige auto-immuunziekte of andere ziekten die permanente immunosuppressieve therapie vereisen
  • Myocardinfarct, ongecontroleerde hypertensie, onstabiele angina, hartritmestoornissen waarvoor medicatie nodig is en/of symptomatisch congestief hartfalen (New York Heart Association > klasse II) binnen 12 maanden
  • Voorafgaande behandeling met een taxaan voor mCRPC
  • Grote operatie en/of bestraling binnen 4 weken

  • Voorgeschiedenis of bewijs van infectie met ernstig acuut respiratoir syndroom coronavirus 2 (SARS-CoV-2), tenzij overeengekomen met medische monitor en als aan de volgende criteria wordt voldaan:

    • Negatieve test op SARS-CoV-2 RNA door real-time polymerasekettingreactie (RT-PCR) binnen 72 uur na de eerste dosis Acapatamab (of AMG 404 in deel 3)
    • Geen acute symptomen van de ziekte van COVID-19 binnen 10 dagen voorafgaand aan de eerste dosis Acapatamab (of AMG 404 in deel 3) (geteld vanaf de dag van positieve test voor asymptomatische proefpersonen)

Eerdere/gelijktijdige klinische studie-ervaring

  • Wordt momenteel behandeld in een ander onderzoeksapparaat of geneesmiddelonderzoek, of minder dan 4 weken sinds het beëindigen van de behandeling met een ander onderzoekshulpmiddel of geneesmiddelonderzoek. Andere onderzoeksprocedures tijdens deelname aan dit onderzoek zijn uitgesloten met uitzondering van onderzoeksscans.

Alleen subprotocol A:

Inclusiecriteria

• Proefpersonen die voor het eerst enzalutamide willen krijgen voor mCRPC

Uitsluitingscriteria

  • Gebruik van sterke CYP2C8-remmers of sterke CYP3A4-inductoren
  • Gebruik van geneesmiddelen met een smalle therapeutische index die substraten zijn van CYP3A4, CYP2C9 of CYP2C19

Alleen subprotocol B:

Inclusiecriteria

  • Proefpersonen die van plan zijn om voor het eerst abirateron te krijgen voor mCRPC-uitsluitingscriteria
  • Baseline matige en ernstige leverfunctiestoornis (Child-Pugh klasse B en C)
  • Aanwezigheid van ongecontroleerde hypertensie, hypokaliëmie of vochtretentie
  • Geschiedenis of aanwezigheid van bijnierschorsinsufficiëntie
  • Gebruik van gelijktijdige medicatie die gevoelige substraten zijn voor CYP2D6 met een smalle therapeutische index
  • Gebruik van sterke CYP3A4-inductoren

Alleen subprotocol C:

Inclusiecriteria

  • Proefpersonen die ongevoelig zijn voor een nieuwe antiandrogeentherapie. Proefpersonen moeten niet in aanmerking komen voor taxaantherapie of deze weigeren.
  • Bewijs van progressieve ziekte, gedefinieerd als 1 of meer PCWG3-criteria: PSA-waarde >/=1 ng/ml die is toegenomen bij ten minste 2 opeenvolgende gelegenheden met een tussenpoos van ten minste 1 week, nodale of viscerale progressie zoals gedefinieerd door RECIST 1.1 met PCGW3-modificaties, en/of verschijnen van 2 of meer nieuwe laesies in botscan Uitsluitingscriteria
  • Geschiedenis of bewijs van interstitiële longziekte of actieve, niet-infectieuze pneumonitis
  • Proefpersonen op een eerdere PD-1- of PD-L1-remmer die vóór de eerste dag van de dosis een immuungerelateerde bijwerking van graad 3 of hoger ondervonden

Alleen subprotocol D:

Inclusiecriteria

  • Proefpersonen hebben mogelijk nieuwe hormonale therapieën gehad (NHT; bijv. Abirateron, enzalutamide, apalutamide of darolutamide) voor prostaatkanker, maar niet meer dan 1 NHT voor gemetastaseerde prostaatkanker
  • Komt niet in aanmerking voor taxaantherapie of weigert taxaantherapie

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Sequentiële toewijzing
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Acapatamab en Enzalutamide: dosisonderzoek
Het dosis-exploratiegedeelte van de studie zal de MTD/aanbevolen fase 2-dosis (RP2D) van acapatamab in combinatie met enzalutamide schatten.
Geneesmiddel: Acapatamab
Acapatamab zal worden toegediend als een intraveneuze (IV) infusie.
Andere namen:
  • PSMA gerichte therapie
Geneesmiddel: Enzalutamide
Enzalutamide zal oraal worden toegediend.
Andere namen:
  • Androgeenreceptorremmer
Experimenteel: Acapatamab en Enzalutamide: dosisuitbreiding
Na dosisonderzoek zal dosisexpansie worden uitgevoerd om de veiligheid en verdraagbaarheid van de geselecteerde dosis te bevestigen en om de werkzaamheid van Acapatamab in combinatie met enzalutamide verder te evalueren.
Geneesmiddel: Acapatamab
Acapatamab zal worden toegediend als een intraveneuze (IV) infusie.
Andere namen:
  • PSMA gerichte therapie
Geneesmiddel: Enzalutamide
Enzalutamide zal oraal worden toegediend.
Andere namen:
  • Androgeenreceptorremmer
Experimenteel: Acapatamab en Abiraterone: dosisonderzoek
Het dosisonderzoeksgedeelte van het onderzoek zal de MTD/aanbevolen fase 2-dosis (RP2D) van acapatamab in combinatie met abirateron schatten.
Geneesmiddel: Acapatamab
Acapatamab zal worden toegediend als een intraveneuze (IV) infusie.
Andere namen:
  • PSMA gerichte therapie
Geneesmiddel: Abirateron
Abiraterone zal oraal worden toegediend.
Andere namen:
  • Cytochroom P450 (CYP)17-remmer
Experimenteel: Acapatamab en Abiraterone: dosisuitbreiding
Na dosisonderzoek zal dosisexpansie worden uitgevoerd om de veiligheid en verdraagbaarheid van de geselecteerde dosis te bevestigen en om de werkzaamheid van acapatamab in combinatie met abirateron verder te evalueren.
Geneesmiddel: Acapatamab
Acapatamab zal worden toegediend als een intraveneuze (IV) infusie.
Andere namen:
  • PSMA gerichte therapie
Geneesmiddel: Abirateron
Abiraterone zal oraal worden toegediend.
Andere namen:
  • Cytochroom P450 (CYP)17-remmer
Experimenteel: Acapatamab en AMG 404: dosisonderzoek
Het dosis-exploratiegedeelte van de studie zal de MTD/RP2D van Acapatamab in combinatie met AMG 404 schatten.
Geneesmiddel: Acapatamab
Acapatamab zal worden toegediend als een intraveneuze (IV) infusie.
Andere namen:
  • PSMA gerichte therapie
Geneesmiddel: AMG 404
AMG 404 zal worden toegediend als een intraveneuze (IV) infusie.
Andere namen:
  • PD-1-remmer
Experimenteel: Acapatamab en AMG 404: dosisuitbreiding
Na dosisonderzoek zal dosisuitbreiding worden uitgevoerd om de veiligheid en verdraagbaarheid van de geselecteerde dosis te bevestigen en om de werkzaamheid van Acapatamab in combinatie met AMG 404 verder te evalueren.
Geneesmiddel: Acapatamab
Acapatamab zal worden toegediend als een intraveneuze (IV) infusie.
Andere namen:
  • PSMA gerichte therapie
Geneesmiddel: AMG 404
AMG 404 zal worden toegediend als een intraveneuze (IV) infusie.
Andere namen:
  • PD-1-remmer
Actieve vergelijker: AMG 404 Monotherapie
AMG 404-monotherapie wordt uitgevoerd om de voorlopige antitumoractiviteit van PD-1-remming in de mCRPC-populatie te evalueren.
Geneesmiddel: AMG 404
AMG 404 zal worden toegediend als een intraveneuze (IV) infusie.
Andere namen:
  • PD-1-remmer
Experimenteel: Acapatamab en Enzalutamide: dosisuitbreiding Azië-cohort
Na dosisonderzoek zal dosisexpansie worden uitgevoerd in het Azië-cohort bij de combinatie MTD/RP2D bepaald in dosisonderzoek om de veiligheid, verdraagbaarheid en farmacokinetiek van acapatamab in combinatie met enzalutamide voor proefpersonen in Azië te bevestigen.
Geneesmiddel: Acapatamab
Acapatamab zal worden toegediend als een intraveneuze (IV) infusie.
Andere namen:
  • PSMA gerichte therapie
Geneesmiddel: Enzalutamide
Enzalutamide zal oraal worden toegediend.
Andere namen:
  • Androgeenreceptorremmer
Experimenteel: Acapatamab en Abiraterone: dosisuitbreiding Azië-cohort
Na dosisonderzoek zal dosisexpansie worden uitgevoerd in het Azië-cohort bij de combinatie MTD/RP2D bepaald in dosisonderzoek om de veiligheid, verdraagbaarheid en farmacokinetiek van acapatamab in combinatie met abirateron voor proefpersonen in Azië te bevestigen.
Geneesmiddel: Acapatamab
Acapatamab zal worden toegediend als een intraveneuze (IV) infusie.
Andere namen:
  • PSMA gerichte therapie
Geneesmiddel: Abirateron
Abiraterone zal oraal worden toegediend.
Andere namen:
  • Cytochroom P450 (CYP)17-remmer
Experimenteel: Acapatamab en AMG 404: dosisuitbreiding Azië-cohort
Na dosisonderzoek zal dosisuitbreiding worden uitgevoerd in het Azië-cohort bij de combinatie MTD/RP2D bepaald in dosisonderzoek om de veiligheid, verdraagbaarheid en farmacokinetiek van Acapatamab in combinatie met AMG 404 voor proefpersonen in Azië te bevestigen.
Geneesmiddel: Acapatamab
Acapatamab zal worden toegediend als een intraveneuze (IV) infusie.
Andere namen:
  • PSMA gerichte therapie
Geneesmiddel: AMG 404
AMG 404 zal worden toegediend als een intraveneuze (IV) infusie.
Andere namen:
  • PD-1-remmer
Experimenteel: Monotherapie met Acapatamab
Monotherapie met acapatamab wordt uitgevoerd om de veiligheid, verdraagbaarheid, farmacokinetiek (PK), farmacodynamiek en werkzaamheid van acapatamab bij proefpersonen met mCRPC te evalueren.
Geneesmiddel: Acapatamab
Acapatamab zal worden toegediend als een intraveneuze (IV) infusie.
Andere namen:
  • PSMA gerichte therapie

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
Tijdsspanne: Cycle 1: Day 1 to Day 28 (28-day cycle)

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:

  • Grade 5 toxicity
  • Grade 4 thrombocytopenia
  • Grade 3 thrombocytopenia with significant hemorrhage
  • Grade 4 neutropenia > 5 days
  • Febrile neutropenia
  • Grade 3 anemia requiring transfusion
  • Grade ≥3 non-hematologic toxicity (with exceptions per protocol)
  • Aspartate transaminase/alanine transaminase >3x upper limit of normal (ULN) with serum total bilirubin >2x ULN without cholestasis or another clear cause
  • Grade ≥3 non-hematological toxicity delaying treatment > 2 weeks or resulting in <75% dose administration.

The complete list of DLTs are described in the protocol
Cycle 1: Day 1 to Day 28 (28-day cycle)
Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and Treatment-related AEs
Tijdsspanne: 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

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
Subprotocol D: Number of Participants Who Experienced TEAEs and Treatment-related AEs
Tijdsspanne: 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

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
Subprotocol C, Part 3: Objective Response Rate (ORR)
Tijdsspanne: 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
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.
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
Subprotocol C, Part 3: Percentage of Participants Who Experienced a Circulating Tumor Cell 0 (CTC0) Response
Tijdsspanne: 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)
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.
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)
Subprotocol C, Part 3: Percentage of Participants Who Experienced a CTC Conversion Response
Tijdsspanne: 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)
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.
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)
Subprotocol C, Part 3: Percentage of Participants Who Experienced a Prostate Specific Antigen (PSA) Response
Tijdsspanne: 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)

A PSA response was defined as the below and must have been confirmed by a second consecutive value 3 weeks later:

  • PSA 30 response: ≥ 30% reduction from the baseline PSA.
  • PSA 50 response: ≥ 50% reduction from the baseline PSA.
  • PSA 70 response: ≥ 70% reduction from the baseline PSA.
  • PSA 90 response: ≥ 90% reduction from the baseline PSA.

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)

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Subprotocols A. B, C (Parts 1 and 2) and D: ORR
Tijdsspanne: 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)
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.
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)
Subprotocols A, B, C (Parts 1 and 2) and D: Percentage of Participants Who Experienced a CTC0 Response
Tijdsspanne: 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)
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.
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)
Subprotocols A, B, C (Parts 1 and 2) and D: Percentage of Participants Who Experienced a CTC Conversion Response
Tijdsspanne: 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)
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.
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)
Subprotocols A, B, C (Parts 1 and 2) and D: Percentage of Participants Who Experienced a PSA Response
Tijdsspanne: 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)

A PSA response was defined as the below and must have been confirmed by a second consecutive value 3 weeks later:

  • PSA 30 response: ≥ 30% reduction from the baseline PSA.
  • PSA 50 response: ≥ 50% reduction from the baseline PSA.
  • PSA 70 response: ≥ 70% reduction from the baseline PSA.
  • PSA 90 response: ≥ 90% reduction from the baseline PSA.

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)
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Duration of CTC0 Response
Tijdsspanne: 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)
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.
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)
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Duration of CTC Conversion Response
Tijdsspanne: 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)
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.
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)
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Duration of PSA Response
Tijdsspanne: 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)
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.
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)
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Duration of Response Per RECIST 1.1
Tijdsspanne: 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)
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.
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)
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Overall Survival (OS)
Tijdsspanne: 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)
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.
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)
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Radiographic Progression Free Survival (rPFS)
Tijdsspanne: 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)
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.
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)
Subprotocols A, B, C (Parts 1, 2 and 3) and D: PSA PFS
Tijdsspanne: 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)
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
Tijdsspanne: 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)
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Time to Radiographic Progression
Tijdsspanne: 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:

  • had no PD but death recorded without new anti-cancer therapy;
  • had no PD, death, or new anti-cancer therapy;
  • had PD or death immediately after more than one consecutively missed tumor assessment;
  • started new anti-cancer therapy prior to PD or death, or prior to any other disease assessment if there is no PD or death.

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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)
Subprotocols A, B, C (Parts 1, 2 and 3) and D: Time to Symptomatic Skeletal Events
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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: Time to Reach Cmax (Tmax) of Acapatamab
Tijdsspanne: 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: Terminal Half-life (t1/2z) of Acapatamab
Tijdsspanne: 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)
Subprotocol C, Part 3: Number of Participants Who Experienced TEAEs and Treatment-related AEs
Tijdsspanne: 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

Medewerkers en onderzoekers

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Sponsor

Amgen

Onderzoekers

  • Studie directeur: MD, Amgen

Publicaties en nuttige links

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Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

15 januari 2021

Primaire voltooiing (Werkelijk)

23 oktober 2023

Studie voltooiing (Werkelijk)

23 oktober 2023

Studieregistratiedata

Eerst ingediend

13 november 2020

Eerst ingediend dat voldeed aan de QC-criteria

13 november 2020

Eerst geplaatst (Werkelijk)

17 november 2020

Updates van studierecords

Laatste update geplaatst (Werkelijk)

26 augustus 2026

Laatste update ingediend die voldeed aan QC-criteria

4 augustus 2026

Laatst geverifieerd

1 juli 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 20190505
  • 2020-001305-23 (EudraCT-nummer)

Plan Individuele Deelnemersgegevens (IPD)

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Beschrijving IPD-plan

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IPD-tijdsbestek voor delen

Verzoeken tot het delen van gegevens met betrekking tot deze studie worden overwogen vanaf 18 maanden nadat de studie is beëindigd en ofwel 1) voor het product en de indicatie een vergunning voor het in de handel brengen is verleend in zowel de VS als Europa, of 2) de klinische ontwikkeling van het product en/of de indicatie wordt stopgezet en de gegevens zullen niet worden ingediend bij regelgevende instanties. Er is geen einddatum voor het in aanmerking komen voor het indienen van een verzoek om gegevensuitwisseling voor dit onderzoek.

IPD-toegangscriteria voor delen

Gekwalificeerde onderzoekers kunnen een verzoek indienen met daarin de onderzoeksdoelstellingen, het/de Amgen-product(en) en de Amgen-studie(s) in de reikwijdte, eindpunten/uitkomsten van belang, plan voor statistische analyse, gegevensvereisten, publicatieplan en kwalificaties van de onderzoeker(s). Over het algemeen willigt Amgen geen externe verzoeken in voor individuele patiëntgegevens met als doel veiligheids- en werkzaamheidskwesties die al in de productetikettering aan bod zijn gekomen, opnieuw te evalueren. Verzoeken worden beoordeeld door een commissie van interne adviseurs. Indien niet goedgekeurd, zal een onafhankelijk beoordelingspanel voor gegevensuitwisseling arbitreren en de uiteindelijke beslissing nemen. Na goedkeuring wordt de informatie die nodig is om de onderzoeksvraag te beantwoorden verstrekt onder de voorwaarden van een overeenkomst voor het delen van gegevens. Dit kunnen geanonimiseerde individuele patiëntgegevens en/of beschikbare ondersteunende documenten zijn, die fragmenten van de analysecode bevatten, indien voorzien in de analysespecificaties. Verdere details zijn beschikbaar op de onderstaande URL.

IPD delen Ondersteunend informatietype

  • LEERPROTOCOOL
  • SAP
  • ICF
  • MVO

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

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