BI-1808 als een enkele agent en met pembrolizumab bij de behandeling van geavanceerde maligniteiten (Keynote-D20)
Fase 1/2a Open-label, dosis-escalatie, multicenter, FIH, opeenvolgende cohort, klinische studie van BI-1808, een monoklonaal antilichaam tegen TNFR 2 als enkelvoudige stof en in combinatie met pembrolizumab (MK-3475) bij proefpersonen met Geavanceerde maligniteiten (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),
Studie Overzicht
Toestand
Gedetailleerde beschrijving
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).
Studietype
Inschrijving (Geschat)
Fase
- Fase 2
- Fase 1
Contacten en locaties
Studiecontact
- Naam: Susanne Gertsson
- Telefoonnummer: +46462868550
- E-mail: susanne.gertsson@bioinvent.com
Studie Contact Back-up
- Naam: Mona Welschof, PhD
- Telefoonnummer: +47 97088721
- E-mail: mona.welschof@bioinvent.com
Studie Locaties
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Copenhagen, Denemarken
- Werving
- Rigshospitalet
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Hoofdonderzoeker:
- Kristoffer Staal Rohrberg
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Herlev, Denemarken, 2730
- Werving
- Herlev Hospital
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Hoofdonderzoeker:
- Rikke Løvendahl Eefsen
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Budapest, Hongarije, 1134
- Werving
- Magyar Honvédség-Egészségügyi Központ
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Hoofdonderzoeker:
- Zsuzsanna Pápai
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Budapest, Hongarije, 1077
- Actief, niet wervend
- PRA Health Sciences - Hungary
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Debrecen, Hongarije, 4032
- Ingetrokken
- Debreceni Egyetem Klinikai Központ
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Omsk, Rusland, 644013
- Beëindigd
- Byudzhetnoye Uchrezhdeniye Zdravookhraneniya Omskoy Oblasti - Klinicheskiy Onkologicheskiy Dispanser
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Saint Petersburg, Rusland, 197022
- Ingetrokken
- National Medical Research Center VA Almazov
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Saint Petersburg, Rusland, 197758
- Ingetrokken
- N.N. Petrov National Medical Research Center of Oncology
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Barcelona, Spanje, 08907
- Nog niet aan het werven
- Institut Catala d'oncologia. Hospital Duran I Reynals
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Madrid, Spanje, 28041
- Werving
- Hospital Universitario 12 de Octubre
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Madrid, Spanje, 28040
- Werving
- START Madrid - Hospital Universitario Fundación Jiménez Díaz
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Madrid, Spanje, 28007
- Nog niet aan het werven
- Hospital Universitario Puerta de Hierro-Majadahonda, Madrid,
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Birmingham, Verenigd Koninkrijk
- Werving
- University Hospital Birmingham
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Contact:
- Julia Scarisbrick, Prof.
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Leicester, Verenigd Koninkrijk, LE1 5WW
- Werving
- University Hospitals of Leicester NHS Trust
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Hoofdonderzoeker:
- Harriet Walter
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London, Verenigd Koninkrijk, W1G 6AD
- Werving
- Sarah Cannon Research Institute UK
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Hoofdonderzoeker:
- Anja Williams
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London, Verenigd Koninkrijk, SE1 9RT
- Werving
- Guy's and Saint Thomas' NHS Foundation Trust
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Hoofdonderzoeker:
- Stephen Morris
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London, Verenigd Koninkrijk
- Werving
- The Royal Marsden Hospital NHS Foundation Trust
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Hoofdonderzoeker:
- Juanita Lopez
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Manchester, Verenigd Koninkrijk, M20 4BX
- Werving
- The Christie NHS Foundation Trust
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Hoofdonderzoeker:
- Richard Cowan
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Southampton, Verenigd Koninkrijk, SO16 6YD
- Werving
- Southampton General Hospital
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Hoofdonderzoeker:
- Sean Lim
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California
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Duarte, California, Verenigde Staten, 91010
- Werving
- City of Hope National Medical Center
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Hoofdonderzoeker:
- Christiane Querfeld
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New York
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New York, New York, Verenigde Staten, 10021
- Werving
- Memorial Sloan Kettering Cancer Center
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Contact:
- Jasmine Zain
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Pennsylvania
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Philadelphia, Pennsylvania, Verenigde Staten, 19104
- Werving
- University of Pennsylvania
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Hoofdonderzoeker:
- Stefan Barta
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Gothenburg, Zweden, 41345
- Werving
- Sahlgrenska University Hospital
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Hoofdonderzoeker:
- Edvard Abel
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Lund, Zweden, 223 70
- Werving
- Skanes University Hospital
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Hoofdonderzoeker:
- Ana Carnerio
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Stockholm, Zweden, 17176
- Werving
- Karolinska University Hospital, Solna
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Hoofdonderzoeker:
- Jeffrey Yachnin
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Sequentiële toewijzing
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: 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 |
|
Experimenteel: 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. |
|
Experimenteel: 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 |
|
Experimenteel: 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. |
|
Experimenteel: 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. |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Occurrence of adverse events (AEs)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: Up to 104 weeks (2 years)
|
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,
Tijdsspanne: 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)
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Evaluation of PK parameters for BI-1808. Maximum observed plasma concentration (Cmax)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)
|
Medewerkers en onderzoekers
Sponsor
Medewerkers
Onderzoekers
- Studie directeur: Andres McAllister, PhD, BioInvent International AB
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Urogenitale ziekten
- Genitale ziekten
- Endocriene systeemziekten
- Urogenitale neoplasmata
- Neoplasmata per site
- Neoplasmata
- Vrouwelijke urogenitale ziekten
- Vrouwelijke urogenitale ziekten en zwangerschapscomplicaties
- Ziekten van het immuunsysteem
- Neoplasmata per histologisch type
- Genitale ziekten, vrouw
- Endocriene klierneoplasmata
- Ovariële ziekten
- Adnexale ziekten
- Genitale neoplasmata, vrouwelijk
- Gonadale aandoeningen
- Huidziektes
- Lymfatische ziekten
- Lymfoproliferatieve aandoeningen
- Immunoproliferatieve aandoeningen
- Lymfoom, non-Hodgkin
- Neuro-ectodermale tumoren
- Neoplasmata, kiemcellen en embryonaal
- Neoplasmata, zenuwweefsel
- Lymfoom
- Neuro-endocriene tumoren
- Nevi en melanomen
- Huidneoplasmata
- Huid- en bindweefselaandoeningen
- Hemische en lymfatische ziekten
- Ovariumneoplasmata
- Melanoma
- Lymfoom, T-cel
- Organische chemicaliën
- Farmaceutische voorbereidingen
- Therapeutica
- Routes voor het toedienen van geneesmiddelen
- Drugstherapie
- Koolwaterstoffen
- Cycloparaffins
- Koolwaterstoffen, alicyclisch
- Koolwaterstoffen, cyclisch
- Terpenen
- Taxoids
- Cyclodecanes
- Diterpenen
- Paclitaxel
- Injecties
- pembrolizumab
- Oplossingen
Andere studie-ID-nummers
- 19-BI-1808-01
- MK3475-D20 (Andere identificatie: Merck Sharp & Dohme Corp)
- 2023-509847-29-00 (Ctis)
- 2023 (Subsidie/contract van de Amerikaanse NIH)
Plan Individuele Deelnemersgegevens (IPD)
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