- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT04631601
Innocuité et efficacité des thérapies pour le cancer de la prostate métastatique résistant à la castration (mCRPC)
Un protocole principal évaluant l'innocuité et l'efficacité des thérapies pour le cancer de la prostate métastatique résistant à la castration (mCRPC)
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
Type d'étude
Inscription (Réel)
Phase
- Phase 2
- La phase 1
Contacts et emplacements
Lieux d'étude
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New South Wales
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Darlinghurst, New South Wales, Australie, 2010
- St Vincents Hospital Sydney
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København Ø, Danemark, 2100
- Rigshospitalet
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Navarre
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Pamplona, Navarre, Espagne, 31008
- Clinica Universidad de Navarra
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Sutton, Royaume-Uni, SM2 5PT
- Royal Marsden Hospital
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Lund, Suède, 221 85
- Skånes universitetssjukhus
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Stockholm, Suède, 171 76
- Karolinska Universitetssjukhuset Solna
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Uppsala, Suède, 75185
- Akademiska Sjukhuset
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Alabama
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Birmingham, Alabama, États-Unis, 35294
- University of Alabama at Birmingham
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California
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Orange, California, États-Unis, 92868
- University of California at Irvine Medical Center
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San Francisco, California, États-Unis, 94158
- University of California San Francisco Mission Bay Campus
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Illinois
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Chicago, Illinois, États-Unis, 60637
- University of Chicago
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Kentucky
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Louisville, Kentucky, États-Unis, 40207
- Norton Cancer Institute
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Texas
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Dallas, Texas, États-Unis, 75390
- University of Texas Southwestern Medical Center
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Houston, Texas, États-Unis, 77030
- University of Texas MD Anderson Cancer Center
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
La description
Toutes les parties
Critère d'intégration:
- ≥ 18 ans (ou l'âge adulte légal dans le pays)
- Le sujet a fourni son consentement éclairé avant le début de toute activité / procédure spécifique à l'étude
- Sujets atteints de mCRPC avec un adénocarcinome de la prostate confirmé histologiquement ou cytologiquement
- Les sujets doivent avoir subi une orchidectomie bilatérale ou doivent suivre un traitement continu de privation androgénique avec un agoniste ou un antagoniste de l'hormone de libération des gonadotrophines (testostérone ≤ 50 ng/dL (ou 1,7 nmol/L))
Critère d'exclusion:
- Métastases du système nerveux central (SNC) ou maladie leptoméningée
- Antécédents ou présence d'une pathologie du SNC cliniquement pertinente
- Antécédents confirmés ou maladie auto-immune actuelle ou autres maladies nécessitant un traitement immunosuppresseur permanent
- Infarctus du myocarde, hypertension non contrôlée, angor instable, arythmie cardiaque nécessitant des médicaments et/ou insuffisance cardiaque congestive symptomatique (New York Heart Association > classe II) dans les 12 mois
- Traitement préalable avec un taxane pour mCRPC
- Chirurgie majeure et/ou radiothérapie dans les 4 semaines
Antécédents ou preuve d'infection par le coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2), sauf accord avec le moniteur médical et répondant aux critères suivants :
- Test négatif pour l'ARN du SRAS-CoV-2 par réaction en chaîne par polymérase en temps réel (RT-PCR) dans les 72 heures suivant la première dose d'Acapatamab (ou AMG 404 dans la partie 3)
- Aucun symptôme aigu de la maladie COVID-19 dans les 10 jours précédant la première dose d'Acapatamab (ou AMG 404 dans la partie 3) (compté à partir du jour du test positif pour les sujets asymptomatiques)
Expérience d'étude clinique antérieure / simultanée
- Reçoit actuellement un traitement dans un autre dispositif expérimental ou étude de médicament, ou moins de 4 semaines depuis la fin du traitement sur un autre dispositif expérimental ou étude(s) de médicament. Les autres procédures d'investigation lors de la participation à cette étude sont exclues à l'exception des scanners d'investigation.
Sous-protocole A uniquement :
Critère d'intégration
• Sujets prévoyant de recevoir de l'enzalutamide pour la première fois pour un CPRCm
Critère d'exclusion
- Utilisation d'inhibiteurs puissants du CYP2C8 ou d'inducteurs puissants du CYP3A4
- Utilisation de médicaments à index thérapeutique étroit qui sont des substrats du CYP3A4, du CYP2C9 ou du CYP2C19
Sous-protocole B uniquement :
Critère d'intégration
- Sujets prévoyant de recevoir de l'abiratérone pour la première fois pour le mCRPC Critères d'exclusion
- Insuffisance hépatique modérée et sévère de base (Child-Pugh Classe B et C)
- Présence d'hypertension non contrôlée, d'hypokaliémie ou de rétention d'eau
- Antécédents ou présence d'insuffisance corticosurrénalienne
- Utilisation concomitante de médicaments qui sont des substrats sensibles du CYP2D6 avec un index thérapeutique étroit
- Utilisation d'inducteurs puissants du CYP3A4
Sous-protocole C uniquement :
Critère d'intégration
- Sujets réfractaires à une nouvelle thérapie anti-androgène. Les sujets doivent être inéligibles ou refuser la thérapie aux taxanes.
- Preuve d'une maladie évolutive, définie par 1 ou plusieurs critères PCWG3 : taux de PSA >/= 1 ng/mL qui a augmenté à au moins 2 occasions successives à au moins 1 semaine d'intervalle, progression nodale ou viscérale telle que définie par RECIST 1.1 avec modifications PCGW3, et/ou apparition d'au moins 2 nouvelles lésions à la scintigraphie osseuse Critères d'exclusion
- Antécédents ou signes de maladie pulmonaire interstitielle ou de pneumonie active non infectieuse
- Sujets sous inhibiteur PD-1 ou PD-L1 antérieur qui ont subi un événement indésirable lié au système immunitaire de grade 3 ou plus avant le premier jour de la dose
Sous-protocole D uniquement :
Critère d'intégration
- Les sujets peuvent avoir reçu de nouveaux traitements hormonaux (NHT ; par exemple, l'abiratérone, l'enzalutamide, l'apalutamide ou le darolutamide) pour le cancer de la prostate, mais pas plus de 1 NHT pour le cancer de la prostate métastatique
- Inadmissible ou refusant la thérapie aux taxanes
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation séquentielle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: Acapatamab et Enzalutamide : exploration de la dose
La partie d'exploration de dose de l'étude permettra d'estimer la DMT/la dose de phase 2 recommandée (RP2D) d'Acapatamab en association avec l'enzalutamide.
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L'acapatamab sera administré en perfusion intraveineuse (IV).
Autres noms:
L'enzalutamide sera administré par voie orale.
Autres noms:
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Expérimental: Acapatamab et Enzalutamide : extension de la dose
Suite à l'exploration de la dose, une extension de la dose sera effectuée pour confirmer l'innocuité et la tolérabilité de la dose sélectionnée et pour évaluer plus avant l'efficacité de l'acapatamab en association avec l'enzalutamide.
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L'acapatamab sera administré en perfusion intraveineuse (IV).
Autres noms:
L'enzalutamide sera administré par voie orale.
Autres noms:
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Expérimental: Acapatamab et Abiratérone : Exploration des doses
La partie exploration de la dose de l'étude permettra d'estimer la DMT/la dose de phase 2 recommandée (RP2D) d'Acapatamab en association avec l'abiratérone.
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L'acapatamab sera administré en perfusion intraveineuse (IV).
Autres noms:
L'abiratérone sera administrée par voie orale.
Autres noms:
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Expérimental: Acapatamab et Abiratérone : extension de la dose
Suite à l'exploration de la dose, une extension de la dose sera effectuée pour confirmer l'innocuité et la tolérabilité de la dose sélectionnée et pour évaluer plus avant l'efficacité de l'acapatamab en association avec l'abiratérone.
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L'acapatamab sera administré en perfusion intraveineuse (IV).
Autres noms:
L'abiratérone sera administrée par voie orale.
Autres noms:
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Expérimental: Acapatamab et AMG 404 : Exploration des doses
La partie d'exploration de dose de l'étude estimera le MTD/RP2D de l'Acapatamab en association avec l'AMG 404.
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L'acapatamab sera administré en perfusion intraveineuse (IV).
Autres noms:
L'AMG 404 sera administré en perfusion intraveineuse (IV).
Autres noms:
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Expérimental: Acapatamab et AMG 404 : extension de dose
Après l'exploration de la dose, une extension de la dose sera effectuée pour confirmer l'innocuité et la tolérabilité de la dose sélectionnée et pour évaluer plus avant l'efficacité de l'acapatamab en association avec l'AMG 404.
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L'acapatamab sera administré en perfusion intraveineuse (IV).
Autres noms:
L'AMG 404 sera administré en perfusion intraveineuse (IV).
Autres noms:
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Comparateur actif: AMG 404 Monothérapie
La monothérapie AMG 404 est en cours pour évaluer l'activité anti-tumorale préliminaire de l'inhibition de PD-1 dans la population mCRPC.
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L'AMG 404 sera administré en perfusion intraveineuse (IV).
Autres noms:
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Expérimental: Acapatamab et Enzalutamide : Cohorte d'expansion de la dose en Asie
Suite à l'exploration de la dose, l'expansion de la dose sera menée dans la cohorte asiatique à la combinaison MTD/RP2D déterminée lors de l'exploration de la dose pour confirmer l'innocuité, la tolérabilité et la pharmacocinétique de l'acapatamab en association avec l'enzalutamide pour les sujets en Asie.
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L'acapatamab sera administré en perfusion intraveineuse (IV).
Autres noms:
L'enzalutamide sera administré par voie orale.
Autres noms:
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Expérimental: Acapatamab et Abiratérone : Cohorte d'expansion de la dose en Asie
Après l'exploration de la dose, l'expansion de la dose sera menée dans la cohorte asiatique à la combinaison MTD/RP2D déterminée lors de l'exploration de la dose pour confirmer l'innocuité, la tolérabilité et la pharmacocinétique de l'acapatamab en association avec l'abiratérone pour les sujets en Asie.
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L'acapatamab sera administré en perfusion intraveineuse (IV).
Autres noms:
L'abiratérone sera administrée par voie orale.
Autres noms:
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Expérimental: Acapatamab et AMG 404 : Cohorte d'expansion de la dose en Asie
Après l'exploration de la dose, l'expansion de la dose sera menée dans la cohorte asiatique à la combinaison MTD/RP2D déterminée lors de l'exploration de la dose pour confirmer l'innocuité, la tolérabilité et la pharmacocinétique de l'Acapatamab en association avec l'AMG 404 pour les sujets en Asie.
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L'acapatamab sera administré en perfusion intraveineuse (IV).
Autres noms:
L'AMG 404 sera administré en perfusion intraveineuse (IV).
Autres noms:
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Expérimental: Acapatamab en monothérapie
La monothérapie à l'acapatamab est menée pour évaluer l'innocuité, la tolérabilité, la pharmacocinétique (PK), la pharmacodynamique et l'efficacité de l'acapatamab chez les sujets atteints de CPRCm.
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L'acapatamab sera administré en perfusion intraveineuse (IV).
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
Délai: 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
Délai: 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
Délai: 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)
Délai: 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
Délai: 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
Délai: 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
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Subprotocols A. B, C (Parts 1 and 2) and D: ORR
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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)
Délai: 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)
Délai: 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
Délai: 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.
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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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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Clinical PFS
Délai: 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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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.
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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
Délai: 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)
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Time to PSA Progression
Délai: 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)
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Time to Subsequent Therapy
Délai: 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)
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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)
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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
Délai: 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
Délai: 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)
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Total Alkaline Phosphatase Levels
Délai: 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.
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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).
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Bone Specific Alkaline Phosphatase Levels
Délai: 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.
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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).
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Lactate Dehydrogenase Levels
Délai: 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).
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Hemoglobin Levels
Délai: 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.
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Neutrophil-to-lymphocyte Ratio
Délai: 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.
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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.
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Subprotocols A, B, C (Parts 1, 2 and 3) and D: Urine N-telopeptide Levels
Délai: 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.
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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).
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Subprotocol A, B and C (Parts 1 and 2) and D: Maximum Serum Concentration (Cmax) of Acapatamab
Délai: Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days)
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Serum concentrations of acapatamab were determined using a validated assay.
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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: Area Under the Curve Over the Dosing Interval (AUCtau)
Délai: Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days)
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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
Délai: Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days)
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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
Délai: Cycle 2: Days 1 to 14 (each cycle was 28 days)
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Serum concentrations of acapatamab were determined using a validated assay.
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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
Délai: 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
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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 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
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Termes liés à cette étude
Mots clés
- CPRCm
- Acapatamab
- DEMI-VIE PROLONGÉE (HLE) BITE
- Cancer de la prostate métastatique résistant à la castration
- 68
- Gallium (68Ga)-membrane spécifique de la prostate
- antigène (PSMA)-11 émission de positrons
- tomographie (TEP)/tomodensitométrie (CT)
- et
- 18
- F-fluorodésoxyglucose (FDG) TEP/TDM
- évaluation de réponse basée
- Engager bispécifique des lymphocytes T
- MORDRE
Termes MeSH pertinents supplémentaires
- Blessures et Blessures
- Troubles induits chimiquement
- Empoisonnement
- Morsures et piqûres
- Agents antinéoplasiques immunologiques
- Agents antinéoplasiques
- Effets physiologiques des drogues
- Mécanismes moléculaires d'action pharmacologique
- Hormones, substituts hormonaux et antagonistes hormonaux
- Antagonistes hormonaux
- Antagonistes des androgènes
- Acides aminés, peptides et protéines
- Protéines
- Actions pharmacologiques
- Actions et utilisations chimiques
- Utilisations thérapeutiques
- Enzymes
- Enzymes et coenzymes
- Oxydoréductases
- Cytochromes
- Oxygénases à fonction mixte
- Oxygénases
- Héprotéines
- Inhibiteurs de point de contrôle immunitaire
- Antagonistes des récepteurs androgènes
- abiraterone
- enzalutamide
- Système d'enzyme Cytochrome P-450
Autres numéros d'identification d'étude
- 20190505
- 2020-001305-23 (Numéro EudraCT)
Plan pour les données individuelles des participants (IPD)
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Description du régime IPD
Délai de partage IPD
Critères d'accès au partage IPD
Type d'informations de prise en charge du partage d'IPD
- PROTOCOLE D'ÉTUDE
- SÈVE
- CIF
- RSE
Informations sur les médicaments et les dispositifs, documents d'étude
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