Een studie om verschillende doses BI 764532 te testen bij patiënten met kleincellige longkanker en andere neuro-endocriene tumoren die positief zijn voor Delta-Like Ligand 3 (DLL3).
Een first-in humane fase I, niet-gerandomiseerde, open-label, multi-center dosisescalatiestudie van BI 764532 toegediend door herhaalde intraveneuze infusies bij patiënten met kleincellig longcarcinoom en andere neuro-endocriene neoplasmata die DLL3 tot expressie brengen
This study is open to adults with small cell lung cancer and other neuroendocrine cancers that are positive for the tumour marker delta-like 3 (DLL3). The study is in people with advanced cancer for whom previous treatment was not successful or no standard treatment exists.
The purpose of this study is to find out the highest dose of obrixtamig and the best treatment schedule that people can tolerate. Obrixtamig is an antibody-like molecule (DLL3/CD3 bispecific) that may help the immune system fight cancer. In this study, obrixtamig is given to people for the first time. Interim clinical data are available for obrixtamig.
Participants get obrixtamig either weekly or once every 3 weeks. If there is benefit for the participants and if they can tolerate it, the treatment is given for a maximum of 3 years. During this time, participants visit the study site about 20 times depending on the response to the treatment. Doctors record any unwanted effects and regularly check the general health of the participants.
Studie Overzicht
Toestand
Interventie / Behandeling
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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Cologne, Duitsland, 50937
- Universitätsklinikum Köln (AöR)
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Dresden, Duitsland, 01307
- Technische Universität Dresden
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Würzburg, Duitsland, 97078
- Universitätsklinikum Würzburg AÖR
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Chiba, Kashiwa, Japan, 277-8577
- National Cancer Center Hospital East
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Barcelona, Spanje, 08035
- Hospital Universitari Vall d'Hebron
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Barcelona, Spanje, 08003
- Hospital del Mar
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Pamplona, Spanje, 31008
- Clínica Universidad de Navarra
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Valencia, Spanje, 46010
- Hospital Clinico Universitario de Valencia
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Georgia
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Atlanta, Georgia, Verenigde Staten, 30322
- Winship Cancer Institute
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Maryland
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Baltimore, Maryland, Verenigde Staten, 21201
- University of Maryland School of Medicine
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Missouri
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St Louis, Missouri, Verenigde Staten, 63108
- Washington University School of Medicine
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Pennsylvania
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Pittsburgh, Pennsylvania, Verenigde Staten, 15232
- University of Pittsburgh Medical Center
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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:
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Signed and dated, written informed consent form (ICF2, ICF3 or ICF4) in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) - Good Clinical Practice (GCP) and local legislation prior to any trial-specific procedures, sampling, or analyses.
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Locally advanced or metastatic cancer not amenable to curative treatment; of following histologies:
- Small cell lung carcinoma (SCLC)
- Large cells neuroendocrine lung carcinoma (LCNEC)
- Neuroendocrine carcinoma (NEC) or small cell carcinoma of any other origin
- Tumours must be positive for DLL3 expression (on archived tissue or instudy fresh biopsy) according to central pathology review in order to start obrixtamig
- Patients with tumours with mixed histologies for any above type are eligible only if neuroendocrine carcinoma/small tumor cells component is predominant and represent at least 50% of the overall tumour tissue.
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For back-fill cohorts only: patient has agreed to and signed an IC to provide mandatory pre-treatment and on-treatment fresh tumor biopsy.
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Patient has failed or is not eligible for available standard therapies according to local guidelines. Standard therapies should include at least one line of chemotherapy that should include platinum for patients with small cells carcinoma tumors histologies.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
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At least one evaluable lesion outside of CNS as defined per modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
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Subjects with brain metastases are eligible provided they meet the following criteria:
- Radiotherapy or surgery for brain metastases was completed at least 2 weeks prior to the first administration of obrixtamig
- Patient is off steroids for at least 7 days (physiologic doses of steroids are permitted), and the patient is off anti-epileptic drugs for at least 7 days or on stable doses of anti-epileptic drugs for malignant Central Nervous System (CNS) disease.
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Adequate liver, bone marrow and renal organ function. Further inclusion criteria apply.
Exclusion Criteria:
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Previous treatment with T cell Engager (TcE) or cell therapies targeting DLL3. Other DLL3 targeting agents (like Rovalpituzumab tesirine (RovaT)) are allowed only if DLL3 positivity is documented after completion of treatment with DLL3 targeting agent in post-treatment biopsy.
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Anticoagulant treatment that cannot be safely interrupted based on opinion of the investigator if medically needed (e.g. biopsy).
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Persistent toxicity from previous treatments that has not resolved to = Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (except for alopecia, CTCAE Grade 2 neuropathy, asthenia/fatigue or grade 2 endocrinopathies controlled by replacement therapy).
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Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of obrixtamig. Physiological replacement of steroids is allowed.
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Prior anti-cancer therapy:
- Patients who have been treated with any other anti-cancer drug within 3 weeks or within 5 half-life periods (whichever is shorter) prior to first administration of obrixtamig.
- Patients who have been treated with extensive field radiotherapy including whole brain irradiation within 2 weeks prior to first administration of obrixtamig.
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Other active malignancy that could interfere with the prognosis and treatment of the disease of the study.
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Major surgery within 28 days of first dose obrixtamig.
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Women who are pregnant (including those who are considered to be possibly pregnant based on the investigator's clinical judgement), nursing/breast feeding or who plan to become pregnant or nurse while in the trial or within 60 days after the last dose of study treatment.
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Presence of any infection requiring systemic antimicrobial treatment within 7 days prior to first dose of trial medication. Patients who have any clinical signs of infection within 48 h prior to first dose of trial medication are not eligible.
Further exclusion criteria apply.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: Arm 1: Obrixtamig
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Obrixtamig - parenteral 1
Andere namen:
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Experimenteel: Arm 2: Obrixtamig
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Obrixtamig - parenteral 2
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Arm 1 en Arm 2: Aantal patiënten met DLT's in de MTD-evaluatieperiode
Tijdsspanne: tot 36 maanden
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tot 36 maanden
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Arm 1 and Arm 2: Maximum tolerated dose (MTD)
Tijdsspanne: up to 36 months
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Maximum tolerated dose (MTD) in any studied regimen defined as the highest dose with less than 25% risk of the true Dose Limiting Toxicity (DLT) rate being equal or above 33% during the MTD evaluation period. Separate MTDs will be determined for each Regimen. |
up to 36 months
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Arm 1 en Arm 2: Gebied onder de concentratie-tijdcurve (AUCτ) van de analyt over een uniform doseringsinterval τ
Tijdsspanne: tot 36 maanden
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tot 36 maanden
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Arm 1 and Arm 2: Maximum measured concentration (Cmax) of obrixtamig
Tijdsspanne: up to 36 months
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up to 36 months
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Arm 1 and Arm 2: Objective response based on RECIST 1.1 criteria in patients with measurable disease
Tijdsspanne: up to 36 months
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Objective response based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in patients with measurable disease |
up to 36 months
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Medewerkers en onderzoekers
Sponsor
Publicaties en nuttige links
Nuttige links
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
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
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 1438-0001
- 2019-000729-31 (Register-ID: EudraCT Number)
- 2024-513100-34-00 (Register-ID: CTIS)
- 2019 (Subsidie/contract van de Amerikaanse NIH)
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
Once the criteria in section 'time frame' are fulfilled, researchers can use the following link https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
IPD-tijdsbestek voor delen
One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
IPD-toegangscriteria voor delen
For study documents -upon signing of a 'Document Sharing Agreement'.For study data -1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
IPD delen Ondersteunend informatietype
- LEERPROTOCOOL
- SAP
- MVO
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .