Studie TNB-486 u subjektů s relapsem nebo refrakterním B-buněčným non-Hodgkinovým lymfomem
Multicentrická, fáze 1, otevřená studie s eskalací dávky a expanzí TNB-486, bispecifické protilátky zacílené na CD19 u subjektů s relapsem nebo refrakterním B-buněčným non-Hodgkinovým lymfomem
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).
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
This dose escalation and optimization study, is evaluating the safety, tolerability, PK, PD and clinical activity of AZD0486 monotherapy.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 1
Kontakty a umístění
Studijní místa
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Heidelberg, Austrálie, 3084
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Hobart, Austrálie, 7000
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Melbourne, Austrálie, 3004
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Chūōku, Japonsko, 104-0045
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Kōtoku, Japonsko, 135-8550
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Nagoya, Japonsko, 460-0001
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Yamagata, Japonsko, 990-9585
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Seoul, Jižní Korea, 03080
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Seoul, Jižní Korea, 05505
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Seoul, Jižní Korea, 06351
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Seoul, Jižní Korea, 06591
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Seoul, Jižní Korea, 120-752
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Florida
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Tampa, Florida, Spojené státy, 33612
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Kentucky
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Louisville, Kentucky, Spojené státy, 40207
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New Jersey
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New Brunswick, New Jersey, Spojené státy, 08901
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North Carolina
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Charlotte, North Carolina, Spojené státy, 28204
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Ohio
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Columbus, Ohio, Spojené státy, 43210
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Pennsylvania
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Pittsburgh, Pennsylvania, Spojené státy, 15237
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Texas
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Austin, Texas, Spojené státy, 78704
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Houston, Texas, Spojené státy, 77030
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Wisconsin
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Milwaukee, Wisconsin, Spojené státy, 53226
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Kaohsiung City, Tchaj-wan, 833401
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Kweishan, Tchaj-wan, 333
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Tainan, Tchaj-wan, 704
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Taipei, Tchaj-wan, 10002
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Sekvenční přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: 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 |
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
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Incidence of subjects with Dose-limiting toxicities (DLT)
Časové okno: 28 days
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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
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Incidence of subjects with adverse events (AEs) and/or serious adverse events (SAEs)
Časové okno: From screening until 90 Days after end of treatment
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The incidence, timing, seriousness, and relationship to study treatment of adverse events will be evaluated. |
From screening until 90 Days after end of treatment
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Maximum Observed Serum Concentration of AZD0486 (Cmax)
Časové okno: 4 Weeks
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The maximum observed serum concentration on a concentration time curve. |
4 Weeks
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Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast)
Časové okno: 4 Weeks
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Area under the serum concentration-time curve from time zero to time of last measurable concentration. |
4 Weeks
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Apparent terminal half-life (t1/2) of AZD0486
Časové okno: From screening until 90 Days after end of treatment
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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
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Anti-Lymphoma Activity by Objective Response Rate (ORR)
Časové okno: 48 months
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Objective response rate is defined as the proportion of subjects with a confirmed partial or complete response to treatment |
48 months
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Anti-Lymphoma Activity by Progression-Free Survival (PFS)
Časové okno: 48 months
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Progression-free survival time is defined as the time from the first dose of AZD0486 to progression or death, whichever occurs first |
48 months
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Anti-Lymphoma Activity by Duration of Objective Response (DOR)
Časové okno: 48 months
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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
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Anti-Lymphoma Activity by Clinical Benefit Rate
Časové okno: 48 months
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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
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Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Ředitel studie: David Sermer, MD, AstraZeneca
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- D7400C00006
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
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
Časový rámec sdílení IPD
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:
Kritéria přístupu pro sdílení IPD
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.
Informace o lécích a zařízeních, studijní dokumenty
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Studuje produkt zařízení regulovaný americkým úřadem FDA
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