BI-1808 en tant qu'agent unique et avec pembrolizumab dans le traitement des tumeurs malignes avancées (Keynote-D20)
Phase 1/2a Open-Label, Dose-Escalation, Multicenter, FIH, Consecutive-Cohort, Clinical Trial of BI-1808, a Monoclonal Antibody to TNFR 2 as a Single Agent and in Combination With Pembrolizumab (MK-3475) in Subjects With Malignités avancées (Keynote-D20)
The goal of this first in human clinical trial is to test BI-1808 administered as single agent and in combination with pembrolizumab in subjects with advanced malignancies whose disease has progressed after standard therapy.
The main questions it aims to answer are:
- how safe and tolerable is BI-1808
- what is maximum tolerated or administrated dose
- to determine recommended dose for further clinical trials. Participants will receive infusions of with BI-1808 as a single agent, BI-1808 in combination with pembrolizumab and BI-1808 in combination with pembrolizumab and paclitaxel every 3 weeks.
For the purpose of this study, subjects with advanced malignancies includes subjects with advanced solid tumors and subjects with T-cell lymphoma (TCL),
Aperçu de l'étude
Statut
Les conditions
Description détaillée
This is a Phase 1/2a, dose-escalation, multicenter, first-in-human, consecutive-cohort, open-label study of BI-1808, as a single agent, in combination with pembrolizumab, and in BI-1808 in combination with pembrolizumab and paclitaxel in subjects with advanced malignancies, whose disease has progressed after standard therapy.
The study will consist of 2 phases: a Phase 1 with Parts A and B, and a Phase 2a with Parts A , B and C.
Phase 1 Part A consists of a dose escalation of BI-1808 as a single agent to evaluate safety and tolerability and to determine the RP2D as a single agent (sRP2D) in subjects with advanced malignancies whose disease has progressed after standard therapy.
Phase 1 Part B consists of a dose escalation of BI-1808 in combination with pembrolizumab to evaluate the safety and tolerability of the combination treatment and to allow selection of the RP2D for BI-1808 in combination with pembrolizumab (cRP2D) in subjects with advanced malignancies whose disease has progressed after standard therapy.
Phase 2a will assess BI-1808 administered as a single agent (Part A), in combination with pembrolizumab (Part B), and in combination with pembrolizumab and paclitaxel (Part C) at the respective hypothesized RP2D(s) determined in Phase 1. Phase 2a expansion will be conducted in indication specific signal seeking cohorts and indication specific Dose Optimization Cohorts) of subjects. The Phase 2a study aims to further evaluate the safety and tolerability of BI-1808 as monotherapy (Part A), in combination with pembrolizumab (Part B), and in combination with pembrolizumab and paclitaxel (Part C). Including characterization of the PK and PD profiles of BI-1808, evaluation of preliminary antitumor activity based on ORR, DoR, and progression-free survival (PFS) as assessed by RECIST v1.1 and iRECIST, and determination of the recommended Phase 2 dose (RP2D).
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
- La phase 1
Contacts et emplacements
Coordonnées de l'étude
- Nom: Susanne Gertsson
- Numéro de téléphone: +46462868550
- E-mail: susanne.gertsson@bioinvent.com
Sauvegarde des contacts de l'étude
- Nom: Mona Welschof, PhD
- Numéro de téléphone: +47 97088721
- E-mail: mona.welschof@bioinvent.com
Lieux d'étude
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Copenhagen, Danemark
- Recrutement
- Rigshospitalet
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Chercheur principal:
- Kristoffer Staal Rohrberg
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Herlev, Danemark, 2730
- Recrutement
- Herlev Hospital
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Chercheur principal:
- Rikke Løvendahl Eefsen
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Barcelona, Espagne, 08907
- Pas encore de recrutement
- Institut Catala d'oncologia. Hospital Duran I Reynals
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Madrid, Espagne, 28041
- Recrutement
- Hospital Universitario 12 de Octubre
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Madrid, Espagne, 28040
- Recrutement
- START Madrid - Hospital Universitario Fundación Jiménez Díaz
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Madrid, Espagne, 28007
- Pas encore de recrutement
- Hospital Universitario Puerta de Hierro-Majadahonda, Madrid,
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Budapest, Hongrie, 1134
- Recrutement
- Magyar Honvédség-Egészségügyi Központ
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Chercheur principal:
- Zsuzsanna Pápai
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Budapest, Hongrie, 1077
- Actif, ne recrute pas
- PRA Health Sciences - Hungary
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Debrecen, Hongrie, 4032
- Retiré
- Debreceni Egyetem Klinikai Központ
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Birmingham, Royaume-Uni
- Recrutement
- University Hospital Birmingham
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Contact:
- Julia Scarisbrick, Prof.
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Leicester, Royaume-Uni, LE1 5WW
- Recrutement
- University Hospitals of Leicester NHS Trust
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Chercheur principal:
- Harriet Walter
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London, Royaume-Uni, W1G 6AD
- Recrutement
- Sarah Cannon Research Institute UK
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Chercheur principal:
- Anja Williams
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London, Royaume-Uni, SE1 9RT
- Recrutement
- Guy's and Saint Thomas' NHS Foundation Trust
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Chercheur principal:
- Stephen Morris
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London, Royaume-Uni
- Recrutement
- The Royal Marsden Hospital NHS Foundation Trust
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Chercheur principal:
- Juanita Lopez
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Manchester, Royaume-Uni, M20 4BX
- Recrutement
- The Christie NHS Foundation Trust
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Chercheur principal:
- Richard Cowan
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Southampton, Royaume-Uni, SO16 6YD
- Recrutement
- Southampton General Hospital
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Chercheur principal:
- Sean Lim
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Omsk, Russie, 644013
- Résilié
- Byudzhetnoye Uchrezhdeniye Zdravookhraneniya Omskoy Oblasti - Klinicheskiy Onkologicheskiy Dispanser
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Saint Petersburg, Russie, 197022
- Retiré
- National Medical Research Center VA Almazov
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Saint Petersburg, Russie, 197758
- Retiré
- N.N. Petrov National Medical Research Center of Oncology
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Gothenburg, Suède, 41345
- Recrutement
- Sahlgrenska University Hospital
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Chercheur principal:
- Edvard Abel
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Lund, Suède, 223 70
- Recrutement
- Skanes University Hospital
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Chercheur principal:
- Ana Carnerio
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Stockholm, Suède, 17176
- Recrutement
- Karolinska University Hospital, Solna
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Chercheur principal:
- Jeffrey Yachnin
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California
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Duarte, California, États-Unis, 91010
- Recrutement
- City of Hope National Medical Center
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Chercheur principal:
- Christiane Querfeld
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New York
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New York, New York, États-Unis, 10021
- Recrutement
- Memorial Sloan Kettering Cancer Center
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Contact:
- Jasmine Zain
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Pennsylvania
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Philadelphia, Pennsylvania, États-Unis, 19104
- Recrutement
- University of Pennsylvania
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Chercheur principal:
- Stefan Barta
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Able and willing to provide written informed consent.
- Aged 18 years or older.
- Histologically confirmed advanced or metastatic malignancy eligible for an enrolling study cohort.
- Disease progression following, intolerance of, ineligibility for, or refusal of applicable standard therapy.
- At least one measurable lesion according to the response criteria specified in the protocol.
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- Life expectancy of at least 12 weeks.
- Adequate organ function.
- Willing and medically suitable to provide required tumor or skin biopsies.
- Meets the disease-specific and treatment-history requirements of the applicable Phase 2a cohort.
- For Phase 2a Part C: Histologically confirmed platinum-resistant high-grade serous or clear-cell ovarian carcinoma, prior platinum-based treatment as specified in the protocol, and suitability for paclitaxel treatment.
Exclusion Criteria:
1. Active central nervous system metastases or carcinomatous meningitis.
- Active or clinically significant autoimmune disease, immunodeficiency, or use of prohibited immunosuppressive treatment.
- Prior treatment-related toxicity not recovered to the level specified in the protocol.
- Prior anticancer therapy, radiotherapy, immunotherapy, investigational treatment, or live vaccine within the protocol-defined washout period.
- History of clinically significant immune-mediated toxicity, including pneumonitis, associated with previous immune-checkpoint inhibitor treatment.
- Uncontrolled or clinically significant cardiovascular disease, serious infection, or another condition that could compromise safety or study participation.
- Major surgery without adequate recovery.
- Prior allogeneic tissue or solid-organ transplantation or active graft-versus-host disease.
- Pregnancy or breastfeeding, or unwillingness to comply with protocol-defined contraceptive requirements.
- Known hypersensitivity to a study treatment or its components.
- Another active malignancy, except for protocol-defined permitted malignancies.
- Participation in another interventional clinical trial that conflicts with this study.
- Unable or unlikely to comply with study procedures and requirements.
- For Phase 2a Part C: Receipt of prohibited colony-stimulating factors within the protocol-defined period before treatment.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation séquentielle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Phase I, Part A - Dose escalation and safety of BI-1808 as single agent
Dose escalation of BI-1808 administrated a single agent |
BI-1808 administered as a flat-dose IV infusion once every 3 weeks |
|
Expérimental: Phase I, Part B - Dose escalation and Safety of BI-1808 in combination with pembrolizumab
Dose escalation of BI-1808 in combination with pembrolizumab. |
BI-1808 administered as a flat-dose IV infusion once every 3 weeks Pembrolizumab administered as a flat-dose IV infusion once every 3 weeks. |
|
Expérimental: Phase 2a - Part A dose expansion of BI-1808 as a single agent
BI-1808 administered as a single agent at the hypothesized recommended phase 2 dose determined in Phase 1 |
BI-1808 administered as a flat-dose IV infusion once every 3 weeks |
|
Expérimental: Phase 2a, Part B - Dose expansion of BI-1808 in combination with pembrolizumab
BI-1808 administered in combination with pembrolizumab at the respective hypothesized recommended phase 2 doses determined in Phase 1 |
BI-1808 administered as a flat-dose IV infusion once every 3 weeks Pembrolizumab administered as a flat-dose IV infusion once every 3 weeks. |
|
Expérimental: Phase 2a, Part C - Dose expansion of BI-1808 in combination with pembrolizumab and paclitaxel
BI-1808 administered in combination with pembrolizumab and paclitaxel at the respective hypothesized recommended phase 2 doses determined in Phase 1. |
BI-1808 administered as a flat-dose IV infusion once every 3 weeks Pembrolizumab administered as a flat-dose IV infusion once every 3 weeks. Paclitaxel administered as a flat-dose IV infusion weekly. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Occurrence of adverse events (AEs)
Délai: From the start of the study treatment for up to 2 years and 90 days.
|
AEs will be assessed by the investigators by severity and will be graded according to the NCI CTCAE v5.0 or higher and causality between AEs and the exposure to the study treatment. |
From the start of the study treatment for up to 2 years and 90 days.
|
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Identify DLTs, determine the maximum tolerated dose and select a recommended Phase 2 dose (RP2D) of BI-1808, given via intravenous (IV) infusion, as a single agent (Phase 1, Part A), and in combination with pembrolizumab (Phase 1, Part B)
Délai: Up to 104 weeks (2 years)
|
Determine the hypothesized RP2D dose for BI-1808 Phase 2a according to mTPI-2 design |
Up to 104 weeks (2 years)
|
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Occurrence of serious adverse events (SAEs)
Délai: Up to 104 weeks (2 years)
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SAEs will be assessed by the investigators by severity and will be graded according to the NCI CTCAE v5.0 or higher and causality between SAEs and the exposure to the study treatment |
Up to 104 weeks (2 years)
|
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To identify the recommended Phase 2 dose (RP2D) of BI-1808,
Délai: up to 104 weeks (2 years)
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Select the RP2D dose for BI-1808 derived from the totality of PK, PD, clinical response, safety,and tolerability observed in signal seeking and dose optimization cohorts. |
up to 104 weeks (2 years)
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Evaluation of PK parameters for BI-1808. Maximum observed plasma concentration (Cmax)
Délai: Up to 104 weeks (2 years)
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Study the PK profile of BI-1808 according to a non-compartmental analysis using a validated software |
Up to 104 weeks (2 years)
|
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Evaluation of ADA response to BI-1808 in serum with validated method
Délai: Up to 104 weeks (2 years)
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The detection and characterization of antibodies to BI-1808 will be performed using a validated method and will be evaluated for BI-1808 serum concentration to enable interpretation of the antibody data |
Up to 104 weeks (2 years)
|
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Measurement of TNFR2 receptor occupancy on CD14+ and/CD16+ cells in serum with validated method
Délai: Up to 104 weeks (2 years)
|
evaluate the receptor occupancy of BI-1808 as a single agent and in combination with pembrolizumab or pembrolizumab and paclitaxel on T-cells expressing TNFR2 in absolute value |
Up to 104 weeks (2 years)
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Directeur d'études: Andres McAllister, PhD, BioInvent International AB
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies urogénitales
- Maladies génitales
- Maladies du système endocrinien
- Tumeurs urogénitales
- Tumeurs par site
- Tumeurs
- Maladies urogénitales féminines
- Maladies urogénitales féminines et complications de la grossesse
- Maladies du système immunitaire
- Tumeurs par type histologique
- Maladies génitales, femme
- Tumeurs des glandes endocrines
- Maladies ovariennes
- Maladies annexielles
- Tumeurs génitales, femme
- Troubles gonadiques
- Maladies de la peau
- Maladies lymphatiques
- Troubles lymphoprolifératifs
- Troubles immunoprolifératifs
- Lymphome non hodgkinien
- Tumeurs neuroectodermiques
- Tumeurs, cellules germinales et embryonnaires
- Tumeurs, tissu nerveux
- Lymphome
- Tumeurs neuroendocrines
- Nevi et mélanomes
- Tumeurs cutanées
- Maladies de la peau et du tissu conjonctif
- Maladies hémiques et lymphatiques
- Tumeurs ovariennes
- Mélanome
- Lymphome à cellules T
- Produits chimiques organiques
- Préparations pharmaceutiques
- Thérapeutique
- Voies d'administration du médicament
- Pharmacothérapie
- Hydrocarbures
- Cycloparaffines
- Hydrocarbures, alicyclique
- Hydrocarbures, cyclique
- Terpènes
- Taxes
- Cyclodécanes
- Diterpènes
- Paclitaxel
- Injections
- pembrolizumab
- Solutions
Autres numéros d'identification d'étude
- 19-BI-1808-01
- MK3475-D20 (Autre identifiant: Merck Sharp & Dohme Corp)
- 2023-509847-29-00 (Ctis)
- 2023 (Subvention/contrat des NIH des États-Unis)
Plan pour les données individuelles des participants (IPD)
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Informations sur les médicaments et les dispositifs, documents d'étude
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