Tutkimus BI 764532:n eri annosten testaamiseksi potilailla, joilla on pienisoluinen keuhkosyöpä ja muita neuroendokriinisia kasvaimia, jotka ovat positiivisia deltakaltaiselle ligandille 3 (DLL3).
Ensimmäinen ihmisen vaiheen I, ei-satunnaistettu, avoin, monikeskus-annoksen eskalaatiokoe BI 764532:sta annettuna toistuvina suonensisäisinä infuusioina potilaille, joilla on pienisoluinen keuhkosyöpä ja muita neuroendokriinisia kasvaimia, jotka ilmentävät DLL3:a
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.
Tutkimuksen yleiskatsaus
Tila
Interventio / Hoito
Opintotyyppi
Ilmoittautuminen (Todellinen)
Vaihe
- Vaihe 1
Yhteystiedot ja paikat
Opiskelupaikat
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-
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Barcelona, Espanja, 08035
- Hospital Universitari Vall d'Hebron
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Barcelona, Espanja, 08003
- Hospital del Mar
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Pamplona, Espanja, 31008
- Clínica Universidad de Navarra
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Valencia, Espanja, 46010
- Hospital Clinico Universitario de Valencia
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-
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Chiba, Kashiwa, Japani, 277-8577
- National Cancer Center Hospital East
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Cologne, Saksa, 50937
- Universitätsklinikum Köln (AöR)
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Dresden, Saksa, 01307
- Technische Universität Dresden
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Würzburg, Saksa, 97078
- Universitätsklinikum Würzburg AÖR
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-
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Georgia
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Atlanta, Georgia, Yhdysvallat, 30322
- Winship Cancer Institute
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Maryland
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Baltimore, Maryland, Yhdysvallat, 21201
- University of Maryland School of Medicine
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Missouri
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St Louis, Missouri, Yhdysvallat, 63108
- Washington University School of Medicine
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Pennsylvania
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Pittsburgh, Pennsylvania, Yhdysvallat, 15232
- University of Pittsburgh Medical Center
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
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.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Ei satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
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Kokeellinen: Arm 1: Obrixtamig
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Obrixtamig - parenteral 1
Muut nimet:
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Kokeellinen: Arm 2: Obrixtamig
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Obrixtamig - parenteral 2
Muut nimet:
|
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Käsivarsi 1 ja käsi 2: DLT-potilaiden määrä MTD-arviointijakson aikana
Aikaikkuna: jopa 36 kuukautta
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jopa 36 kuukautta
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Arm 1 and Arm 2: Maximum tolerated dose (MTD)
Aikaikkuna: 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
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Käsivarsi 1 ja käsivarsi 2: Analyytin pitoisuus-aikakäyrän alla oleva pinta-ala (AUCτ) tasaisella annosteluvälillä τ
Aikaikkuna: jopa 36 kuukautta
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jopa 36 kuukautta
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Arm 1 and Arm 2: Maximum measured concentration (Cmax) of obrixtamig
Aikaikkuna: 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
Aikaikkuna: 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
|
Yhteistyökumppanit ja tutkijat
Sponsori
Julkaisuja ja hyödyllisiä linkkejä
Hyödyllisiä linkkejä
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Todellinen)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
- 1438-0001
- 2019-000729-31 (Rekisterin tunniste: EudraCT Number)
- 2024-513100-34-00 (Rekisterin tunniste: CTIS)
- 2019 (Yhdysvaltain NIH-apuraha/sopimus)
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
IPD-suunnitelman kuvaus
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-jaon aikakehys
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-jaon käyttöoikeuskriteerit
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-jakamista tukeva tietotyyppi
- STUDY_PROTOCOL
- MAHLA
- CSR
Lääke- ja laitetiedot, tutkimusasiakirjat
Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta
Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta
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