BI-1808 come agente singolo e con pembrolizumab nel trattamento dei tumori maligni avanzati (Keynote-D20)
Studio clinico di fase 1/2a in aperto, aumento della dose, multicentrico, FIH, coorte consecutiva di BI-1808, un anticorpo monoclonale contro TNFR 2 come agente singolo e in combinazione con pembrolizumab (MK-3475) in soggetti con Neoplasie avanzate (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),
Panoramica dello studio
Stato
Descrizione dettagliata
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).
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Contatto studio
- Nome: Susanne Gertsson
- Numero di telefono: +46462868550
- Email: susanne.gertsson@bioinvent.com
Backup dei contatti dello studio
- Nome: Mona Welschof, PhD
- Numero di telefono: +47 97088721
- Email: mona.welschof@bioinvent.com
Luoghi di studio
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Copenhagen, Danimarca
- Reclutamento
- Rigshospitalet
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Investigatore principale:
- Kristoffer Staal Rohrberg
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Herlev, Danimarca, 2730
- Reclutamento
- Herlev Hospital
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Investigatore principale:
- Rikke Løvendahl Eefsen
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Birmingham, Regno Unito
- Reclutamento
- University Hospital Birmingham
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Contatto:
- Julia Scarisbrick, Prof.
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Leicester, Regno Unito, LE1 5WW
- Reclutamento
- University Hospitals of Leicester NHS Trust
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Investigatore principale:
- Harriet Walter
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London, Regno Unito, W1G 6AD
- Reclutamento
- Sarah Cannon Research Institute UK
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Investigatore principale:
- Anja Williams
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London, Regno Unito, SE1 9RT
- Reclutamento
- Guy's and Saint Thomas' NHS Foundation Trust
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Investigatore principale:
- Stephen Morris
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London, Regno Unito
- Reclutamento
- The Royal Marsden Hospital NHS Foundation Trust
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Investigatore principale:
- Juanita Lopez
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Manchester, Regno Unito, M20 4BX
- Reclutamento
- The Christie NHS Foundation Trust
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Investigatore principale:
- Richard Cowan
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Southampton, Regno Unito, SO16 6YD
- Reclutamento
- Southampton General Hospital
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Investigatore principale:
- Sean Lim
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Omsk, Russia, 644013
- Terminato
- Byudzhetnoye Uchrezhdeniye Zdravookhraneniya Omskoy Oblasti - Klinicheskiy Onkologicheskiy Dispanser
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Saint Petersburg, Russia, 197022
- Ritirato
- National Medical Research Center VA Almazov
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Saint Petersburg, Russia, 197758
- Ritirato
- N.N. Petrov National Medical Research Center of Oncology
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Barcelona, Spagna, 08907
- Non ancora reclutamento
- Institut Catala d'oncologia. Hospital Duran I Reynals
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Madrid, Spagna, 28041
- Reclutamento
- Hospital Universitario 12 de Octubre
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Madrid, Spagna, 28040
- Reclutamento
- START Madrid - Hospital Universitario Fundación Jiménez Díaz
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Madrid, Spagna, 28007
- Non ancora reclutamento
- Hospital Universitario Puerta de Hierro-Majadahonda, Madrid,
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California
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Duarte, California, Stati Uniti, 91010
- Reclutamento
- City of Hope National Medical Center
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Investigatore principale:
- Christiane Querfeld
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New York
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New York, New York, Stati Uniti, 10021
- Reclutamento
- Memorial Sloan Kettering Cancer Center
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Contatto:
- Jasmine Zain
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Pennsylvania
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Philadelphia, Pennsylvania, Stati Uniti, 19104
- Reclutamento
- University of Pennsylvania
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Investigatore principale:
- Stefan Barta
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Gothenburg, Svezia, 41345
- Reclutamento
- Sahlgrenska University Hospital
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Investigatore principale:
- Edvard Abel
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Lund, Svezia, 223 70
- Reclutamento
- Skanes University Hospital
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Investigatore principale:
- Ana Carnerio
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Stockholm, Svezia, 17176
- Reclutamento
- Karolinska University Hospital, Solna
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Investigatore principale:
- Jeffrey Yachnin
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Budapest, Ungheria, 1134
- Reclutamento
- Magyar Honvédség-Egészségügyi Központ
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Investigatore principale:
- Zsuzsanna Pápai
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Budapest, Ungheria, 1077
- Attivo, non reclutante
- PRA Health Sciences - Hungary
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Debrecen, Ungheria, 4032
- Ritirato
- Debreceni Egyetem Klinikai Központ
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione sequenziale
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: 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 |
|
Sperimentale: 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. |
|
Sperimentale: 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 |
|
Sperimentale: 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. |
|
Sperimentale: 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. |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Occurrence of adverse events (AEs)
Lasso di tempo: From the start of the study treatment for up to 2 years and 90 days.
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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)
Lasso di tempo: Up to 104 weeks (2 years)
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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)
Lasso di tempo: 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,
Lasso di tempo: 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)
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Evaluation of PK parameters for BI-1808. Maximum observed plasma concentration (Cmax)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: Up to 104 weeks (2 years)
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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)
|
Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Direttore dello studio: Andres McAllister, PhD, BioInvent International AB
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie urogenitali
- Malattie genitali
- Malattie del sistema endocrino
- Neoplasie urogenitali
- Neoplasie per sede
- Neoplasie
- Malattie urogenitali femminili
- Malattie urogenitali femminili e complicanze della gravidanza
- Malattie del sistema immunitario
- Neoplasie per tipo istologico
- Malattie genitali, femmina
- Neoplasie delle ghiandole endocrine
- Malattie ovariche
- Malattie annessiali
- Neoplasie genitali, femmina
- Disturbi gonadici
- Malattie della pelle
- Malattie linfatiche
- Malattie linfoproliferative
- Disturbi immunoproliferativi
- Linfoma non Hodgkin
- Tumori neuroectodermici
- Neoplasie, cellule germinali ed embrionali
- Neoplasie, tessuto nervoso
- Linfoma
- Tumori neuroendocrini
- Nevi e melanomi
- Neoplasie cutanee
- Malattie della pelle e del tessuto connettivo
- Malattie emiche e linfatiche
- Neoplasie ovariche
- Melanoma
- Linfoma, cellule T
- Prodotti chimici organici
- Preparati farmaceutici
- Terapie
- Rotte della somministrazione di droga
- Terapia farmacologica
- Idrocarburi
- Cicloparaffins
- Idrocarburi, aliciclici
- Idrocarburi, ciclici
- Terpeni
- Taxoidi
- Ciclodecani
- Diterpenes
- Paclitaxel
- Iniezioni
- pembrolizumab
- Soluzioni
Altri numeri di identificazione dello studio
- 19-BI-1808-01
- MK3475-D20 (Altro identificatore: Merck Sharp & Dohme Corp)
- 2023-509847-29-00 (Ctis)
- 2023 (Sovvenzione/contratto NIH degli Stati Uniti)
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Informazioni su farmaci e dispositivi, documenti di studio
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