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Eine Studie zu TNB-486 bei Patienten mit rezidiviertem oder refraktärem B-Zell-Non-Hodgkin-Lymphom

24. September 2026 aktualisiert von: AstraZeneca

Eine multizentrische Phase-1-Open-Label-Studie zur Dosiseskalation und Expansion von TNB-486, einem bispezifischen Antikörper, der auf CD19 bei Patienten mit rezidiviertem oder refraktärem B-Zell-Non-Hodgkin-Lymphom abzielt

This phase 1 study will investigate the safety, tolerability, pharmacokinetic, pharmacodynamic, and clinical activity of AZD0486, a CD19 x CD3 T-cell engaging bispecific antibody, in subjects with B-cell non-Hodgkin lymphoma (B-NHL).

Studienübersicht

Status

Aktiv, nicht rekrutierend

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

This dose escalation and optimization study, is evaluating the safety, tolerability, PK, PD and clinical activity of AZD0486 monotherapy.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

226

Phase

  • Phase 1

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

  • Australien
      • Heidelberg, Australien, 3084
        • Research Site
      • Hobart, Australien, 7000
        • Research Site
      • Melbourne, Australien, 3004
        • Research Site
  • Japan
      • Chūōku, Japan, 104-0045
        • Research Site
      • Kōtoku, Japan, 135-8550
        • Research Site
      • Nagoya, Japan, 460-0001
        • Research Site
      • Yamagata, Japan, 990-9585
        • Research Site
  • Südkorea
      • Seoul, Südkorea, 03080
        • Research Site
      • Seoul, Südkorea, 05505
        • Research Site
      • Seoul, Südkorea, 06351
        • Research Site
      • Seoul, Südkorea, 06591
        • Research Site
      • Seoul, Südkorea, 120-752
        • Research Site
  • Taiwan
      • Kaohsiung City, Taiwan, 833401
        • Research Site
      • Kweishan, Taiwan, 333
        • Research Site
      • Tainan, Taiwan, 704
        • Research Site
      • Taipei, Taiwan, 10002
        • Research Site
  • Vereinigte Staaten
    • Florida
      • Tampa, Florida, Vereinigte Staaten, 33612
        • Research Site
    • Kentucky
      • Louisville, Kentucky, Vereinigte Staaten, 40207
        • Research Site
    • New Jersey
      • New Brunswick, New Jersey, Vereinigte Staaten, 08901
        • Research Site
    • North Carolina
      • Charlotte, North Carolina, Vereinigte Staaten, 28204
        • Research Site
    • Ohio
      • Columbus, Ohio, Vereinigte Staaten, 43210
        • Research Site
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Vereinigte Staaten, 15237
        • Research Site
    • Texas
      • Austin, Texas, Vereinigte Staaten, 78704
        • Research Site
      • Houston, Texas, Vereinigte Staaten, 77030
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, Vereinigte Staaten, 53226
        • Research Site

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre bis 130 Jahre (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

Inclusion Criteria:

  • Biopsy proven B-NHL, including DLBCL, HGBL, or FL.
  • Relapsed/refractory cohorts:

In order to be eligible subjects must have received at least 2 prior lines of therapy and not be candidates for treatment regimens known to provide clinical benefit in B-NHL. CAR T-naive subjects are allowed if they have declined, are considered ineligible for, or do not have timely access to CAR T cell therapies.

  • 1L FL cohorts: Subject has biopsy-proven FL Grade 1-3a per WHO 2016 classification, Stage II-IV, FL International Prognostic Index 2-5 that has not been treated with prior systemic lymphoma-directed therapy and requires initiation of treatment based on GELF criteria. Radiation to localized disease prior to study entry is allowed if >14 days from first dose.
  • All Cohorts:

Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

  • Subject must have adequate liver, bone marrow and kidney function (eGFR ≥ 50 mL/min).
  • Subject must have locally confirmed CD19 positivity (must be documented after time of progression from last CD19-targeted therapy, if received)
  • Subject must have at least 1 measurable disease site
  • Subject must have ANC >/= 1000/mm3, platelets >/= 50,000 mm3, hemoglobin >/= 8.0 g/dL. Transfusion and/or growth factor are allowed but counts must be stable for at least 72 hours afterwards prior to screening
  • Subject must have a total bilirubin <1.5x ULN, AST/ALT < 3xULN

Exclusion Criteria:

  • Subject has been diagnosed with or treated for another malignancy whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen.
  • Subject has active central nervous system (CNS) involvement by their B-NHL. --Subjects may be eligible with a distant history of CNS involvement that has been adequately treated with no evidence of recurrence within last 6 months from screening.
  • Subject has a history of leukemic presentation of their B-NHL (>5,000 circulating lymphoma cells/uL in the peripheral blood).
  • Subject has history or presence of clinically significant CNS pathology
  • Subject has CNS involvement from active or history of autoimmune disease.
  • Subject received CD19 CAR T therapy within 3 months prior to first dose.
  • Subject experienced Grade ≥ 3 cytokine release syndrome (CRS) following prior T-cell engager (TCE) or CAR T-cell therapy.
  • Subject experienced Grade ≥ 2 neurotoxicity/immune effector cell-associated neurotoxicity syndrome (ICANS) following prior TCE or CAR T-cell therapy.
  • Subject has received a peripheral autologous stem cell transplant (SCT) within 12 weeks, or an allogeneic SCT within 1 year of the first dose of study drug treatment or has received an SCT and requires ongoing immunosuppressive therapy.
  • Subjects with human immunodeficiency virus (HIV) infection, or subjects with chronic or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Subjects with chronic HBV may be enrolled if the HBV viral load is undetectable on suppressive therapy, or if the subject has a documented cure. Subjects with HCV who have a documented cure may be enrolled.
  • Subject has a history of major cardiac abnormalities.
  • If female, subject must not be pregnant or breastfeeding.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: N / A
  • Interventionsmodell: Sequenzielle Zuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: AZD0486 Monotherapy Dose Escalation in Subjects with B-NHL

AZD0486 monotherapy will be administered intravenously on day 1 and 15 of 28 day cycles for a maximum of 2 years or until discontinuation criteria are met. Depending on cohort, subjects may receive priming or step-up dosing administered weekly during cycle 1 before reaching the target dose. Additional cohorts may be opened where subjects receive weekly dosing during Cycles 1-2. While on study, subjects will be monitored for safety and efficacy with periodic disease assessment with PET/CT. If subject achieves two consecutive CRs after completing C6, then they may be eligible for monthly dosing
Arzneimittel: AZD0486 IV

AZD0486 is a bispecific antibody targeting CD19 on tumor cells and CD3 on T-cells leading to T cell-mediated cytotoxicity of malignant B cells

Andere Namen:
  • TNB-486

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Incidence of subjects with Dose-limiting toxicities (DLT)
Zeitfenster: 28 days

A DLT is defined as a TEAE that is not unequivocally due to the subject's underlying malignancy or other extraneous cause. DLT evaluable subjects are defined as those subjects who receive either the target dose of AZD0486 or priming dose(s) in any step-up dose schedule and are assessed for toxicities for the 28-day evaluation period.

The NCI-CTCAE version 5.0 will be used (except for CRS and NT). A DLT will be evaluated as Non-hematologic, Hematologic, Cytokine Release Syndrome (CRS), or neurotoxicity.
28 days
Incidence of subjects with adverse events (AEs) and/or serious adverse events (SAEs)
Zeitfenster: From screening until 90 Days after end of treatment

The incidence, timing, seriousness, and relationship to study treatment of adverse events will be evaluated.
From screening until 90 Days after end of treatment
Maximum Observed Serum Concentration of AZD0486 (Cmax)
Zeitfenster: 4 Weeks

The maximum observed serum concentration on a concentration time curve.
4 Weeks
Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast)
Zeitfenster: 4 Weeks

Area under the serum concentration-time curve from time zero to time of last measurable concentration.
4 Weeks
Apparent terminal half-life (t1/2) of AZD0486
Zeitfenster: From screening until 90 Days after end of treatment

Terminal half-life (t1/2,) will be determined after infusion in Cycle 1 using non-compartmental methods.
From screening until 90 Days after end of treatment

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Anti-Lymphoma Activity by Objective Response Rate (ORR)
Zeitfenster: 48 months

Objective response rate is defined as the proportion of subjects with a confirmed partial or complete response to treatment
48 months
Anti-Lymphoma Activity by Progression-Free Survival (PFS)
Zeitfenster: 48 months

Progression-free survival time is defined as the time from the first dose of AZD0486 to progression or death, whichever occurs first
48 months
Anti-Lymphoma Activity by Duration of Objective Response (DOR)
Zeitfenster: 48 months

The duration of objective response for a subject is defined as the time from the initial objective response to disease progression or death, whichever occurs first
48 months
Anti-Lymphoma Activity by Clinical Benefit Rate
Zeitfenster: 48 months

Clinical benefit rate is defined as the proportion of subjects with a confirmed complete response, partial response or minor response, or stable disease for at least 24 weeks after responding to treatment
48 months

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

AstraZeneca

Ermittler

  • Studienleiter: David Sermer, MD, AstraZeneca

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

2. März 2021

Primärer Abschluss (Geschätzt)

19. Juni 2028

Studienabschluss (Geschätzt)

19. Juni 2028

Studienanmeldedaten

Zuerst eingereicht

13. Oktober 2020

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

13. Oktober 2020

Zuerst gepostet (Tatsächlich)

20. Oktober 2020

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

25. September 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

24. September 2026

Zuletzt verifiziert

1. September 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • D7400C00006

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

JA

Beschreibung des IPD-Plans

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

Supporting

IPD-Sharing-Zeitrahmen

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Access Criteria:

IPD-Sharing-Zugriffskriterien

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Ja

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

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