BI-1808 som enkeltmiddel og med Pembrolizumab til behandling af avancerede maligniteter (Keynote-D20)
Fase 1/2a open-label, dosis-eskalering, multicenter, FIH, konsekutiv kohorte, klinisk forsøg med BI-1808, et monoklonalt antistof mod TNFR 2 som enkeltmiddel og i kombination med Pembrolizumab (MK-3475) hos forsøgspersoner med Avancerede maligniteter (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),
Studieoversigt
Status
Detaljeret beskrivelse
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).
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiekontakt
- Navn: Susanne Gertsson
- Telefonnummer: +46462868550
- E-mail: susanne.gertsson@bioinvent.com
Undersøgelse Kontakt Backup
- Navn: Mona Welschof, PhD
- Telefonnummer: +47 97088721
- E-mail: mona.welschof@bioinvent.com
Studiesteder
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Copenhagen, Danmark
- Rekruttering
- Rigshospitalet
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Ledende efterforsker:
- Kristoffer Staal Rohrberg
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Herlev, Danmark, 2730
- Rekruttering
- Herlev Hospital
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Ledende efterforsker:
- Rikke Løvendahl Eefsen
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Birmingham, Det Forenede Kongerige
- Rekruttering
- University Hospital Birmingham
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Kontakt:
- Julia Scarisbrick, Prof.
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Leicester, Det Forenede Kongerige, LE1 5WW
- Rekruttering
- University Hospitals of Leicester NHS Trust
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Ledende efterforsker:
- Harriet Walter
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London, Det Forenede Kongerige, W1G 6AD
- Rekruttering
- Sarah Cannon Research Institute UK
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Ledende efterforsker:
- Anja Williams
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London, Det Forenede Kongerige, SE1 9RT
- Rekruttering
- Guy's and Saint Thomas' NHS Foundation Trust
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Ledende efterforsker:
- Stephen Morris
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London, Det Forenede Kongerige
- Rekruttering
- The Royal Marsden Hospital NHS Foundation Trust
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Ledende efterforsker:
- Juanita Lopez
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Manchester, Det Forenede Kongerige, M20 4BX
- Rekruttering
- The Christie NHS Foundation Trust
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Ledende efterforsker:
- Richard Cowan
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Southampton, Det Forenede Kongerige, SO16 6YD
- Rekruttering
- Southampton General Hospital
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Ledende efterforsker:
- Sean Lim
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California
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Duarte, California, Forenede Stater, 91010
- Rekruttering
- City of Hope National Medical Center
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Ledende efterforsker:
- Christiane Querfeld
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New York
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New York, New York, Forenede Stater, 10021
- Rekruttering
- Memorial Sloan Kettering Cancer Center
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Kontakt:
- Jasmine Zain
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater, 19104
- Rekruttering
- University of Pennsylvania
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Ledende efterforsker:
- Stefan Barta
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Omsk, Rusland, 644013
- Afsluttet
- Byudzhetnoye Uchrezhdeniye Zdravookhraneniya Omskoy Oblasti - Klinicheskiy Onkologicheskiy Dispanser
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Saint Petersburg, Rusland, 197022
- Trukket tilbage
- National Medical Research Center VA Almazov
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Saint Petersburg, Rusland, 197758
- Trukket tilbage
- N.N. Petrov National Medical Research Center of Oncology
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Barcelona, Spanien, 08907
- Ikke rekrutterer endnu
- Institut Catala d'oncologia. Hospital Duran I Reynals
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Madrid, Spanien, 28041
- Rekruttering
- Hospital Universitario 12 de Octubre
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Madrid, Spanien, 28040
- Rekruttering
- START Madrid - Hospital Universitario Fundación Jiménez Díaz
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Madrid, Spanien, 28007
- Ikke rekrutterer endnu
- Hospital Universitario Puerta de Hierro-Majadahonda, Madrid,
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Gothenburg, Sverige, 41345
- Rekruttering
- Sahlgrenska University Hospital
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Ledende efterforsker:
- Edvard Abel
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Lund, Sverige, 223 70
- Rekruttering
- Skanes University Hospital
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Ledende efterforsker:
- Ana Carnerio
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Stockholm, Sverige, 17176
- Rekruttering
- Karolinska University Hospital, Solna
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Ledende efterforsker:
- Jeffrey Yachnin
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Budapest, Ungarn, 1134
- Rekruttering
- Magyar Honvédség-Egészségügyi Központ
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Ledende efterforsker:
- Zsuzsanna Pápai
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Budapest, Ungarn, 1077
- Aktiv, ikke rekrutterende
- PRA Health Sciences - Hungary
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Debrecen, Ungarn, 4032
- Trukket tilbage
- Debreceni Egyetem Klinikai Központ
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: 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 |
|
Eksperimentel: 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. |
|
Eksperimentel: 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 |
|
Eksperimentel: 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. |
|
Eksperimentel: 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. |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Occurrence of adverse events (AEs)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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,
Tidsramme: 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)
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Evaluation of PK parameters for BI-1808. Maximum observed plasma concentration (Cmax)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
|
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Studieleder: Andres McAllister, PhD, BioInvent International AB
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Urogenitale sygdomme
- Genitale sygdomme
- Sygdomme i det endokrine system
- Urogenitale neoplasmer
- Neoplasmer efter sted
- Neoplasmer
- Urogenitale sygdomme hos kvinder
- Kvinders urogenitale sygdomme og graviditetskomplikationer
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Kønssygdomme, kvindelige
- Neoplasmer i endokrine kirtler
- Ovariesygdomme
- Adnexale sygdomme
- Genitale neoplasmer, kvindelige
- Gonadale lidelser
- Hudsygdomme
- Lymfesygdomme
- Lymfoproliferative lidelser
- Immunproliferative lidelser
- Lymfom, Non-Hodgkin
- Neuroektodermale tumorer
- Neoplasmer, kimceller og embryonale
- Neoplasmer, nervevæv
- Lymfom
- Neuroendokrine tumorer
- Nevi og melanomer
- Neoplasmer i huden
- Hud- og bindevævssygdomme
- Hemiske og lymfatiske sygdomme
- Ovariale neoplasmer
- Melanom
- Lymfom, T-celle
- Organiske kemikalier
- Farmaceutiske præparater
- Terapeutik
- Lægemiddeladministrationsruter
- Lægemiddelterapi
- Kulbrinter
- Cycloparaffiner
- Kulbrinter, alicyklisk
- Kulbrinter, cyklisk
- Terpenes
- Taxoider
- Cyclodecanes
- Diterpenes
- Paclitaxel
- Injektioner
- pembrolizumab
- Løsninger
Andre undersøgelses-id-numre
- 19-BI-1808-01
- MK3475-D20 (Anden identifikator: Merck Sharp & Dohme Corp)
- 2023-509847-29-00 (Ctis)
- 2023 (U.S. NIH-bevilling/kontrakt)
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