A Study to Evaluate the Pharmacokinetics and Safety of Loncastuximab Tesirine in Participants With Relapsed or Refractory Diffuse Large B-cell Lymphoma or High-grade B-cell Lymphoma With Hepatic Impairment (LOTIS-10)

NCT ID: NCT05660395

Last Updated: 2025-07-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-08-28

Study Completion Date

2027-04-05

Brief Summary

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The primary objective of this study is to determine the recommended dosing regimen of loncastuximab tesirine in diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL) participants with moderate and severe hepatic impairment.

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Detailed Description

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Conditions

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Diffuse Large B-Cell Lymphoma High-grade B-cell Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Arm A: Normal Hepatic Function

Participants will receive loncastuximab tesirine 0.15 mg/kg once every 3 weeks (Q3W) for two cycles, then 0.075 mg/kg Q3W for subsequent cycles (1 cycle = 21 days).

Participants who have a toxicity meeting the criteria for dose reduction will have subsequent doses reduced by 50%. If the toxicity recurs, subsequent doses must be reduced by an additional 50%. A maximum of 2 dose reductions are allowed. Participants who have a toxicity meeting the criteria for dose reduction following Cycle 2 will receive the protocol-specified dose of 50% of initiate dose for Cycle 3, i.e., they will not have an additional dose reduction for Cycle 3.

Group Type EXPERIMENTAL

Loncastuximab Tesirine

Intervention Type DRUG

Intravenous (IV) Infusion

Arm B: Moderate Hepatic Impairment

Participants will receive loncastuximab tesirine in a standard 3+3 dose-escalation design. Initial dose will be 0.09 mg/kg Q3W for two cycles, then 0.045 mg/kg Q3W for subsequent cycles (1 cycle = 21 days). The highest dose possibly administered will be 0.15 mg/kg Q3W.

Participants who have a toxicity meeting the criteria for dose reduction will have subsequent doses reduced by 50%. If the toxicity recurs, subsequent doses must be reduced by an additional 50%. A maximum of 2 dose reductions are allowed. Participants who have a toxicity meeting the criteria for dose reduction following Cycle 2 will receive the protocol-specified dose of 50% of initiate dose for Cycle 3, i.e., they will not have an additional dose reduction for Cycle 3.

Group Type EXPERIMENTAL

Loncastuximab Tesirine

Intervention Type DRUG

Intravenous (IV) Infusion

Arm C: Severe Hepatic Impairment

Participants will receive loncastuximab tesirine in a standard 3+3 dose-escalation design. Initial dose will be 0.09 mg/kg Q3W for two cycles, then 0.045 mg/kg Q3W for subsequent cycles (1 cycle = 21 days). The highest dose possibly administered will be 0.15 mg/kg Q3W.

Participants who have a toxicity meeting the criteria for dose reduction will have subsequent doses reduced by 50%. If the toxicity recurs, subsequent doses must be reduced by an additional 50%. A maximum of 2 dose reductions are allowed. Participants who have a toxicity meeting the criteria for dose reduction following Cycle 2 will receive the protocol-specified dose of 50% of initiate dose for Cycle 3, i.e., they will not have an additional dose reduction for Cycle 3.

Group Type EXPERIMENTAL

Loncastuximab Tesirine

Intervention Type DRUG

Intravenous (IV) Infusion

Interventions

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Loncastuximab Tesirine

Intravenous (IV) Infusion

Intervention Type DRUG

Other Intervention Names

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Zynlonta ADCT-402

Eligibility Criteria

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Inclusion Criteria

* Male or female participants aged 18 years or older
* Pathologic diagnosis of relapsed (disease that has recurred following a response) or refractory (disease that failed to respond to prior therapy) DLBCL not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma (2016 World Health Organization classification) who have received at least one systemic treatment regimen
* Measurable disease as defined by the 2014 Lugano Classification
* Normal hepatic function or hepatic impairment as defined by the National Cancer Institute Organ Dysfunction Working Group hepatic impairment classification:

* Arm A Normal hepatic function: bilirubin and aspartate aminotransferase (AST) ≤ upper limit of normal (ULN)
* Arm B Moderate hepatic impairment: bilirubin \> 1.5 × to 3 × ULN (any AST)
* Arm C Severe hepatic impairment: bilirubin \> 3 × ULN (any AST)
* ECOG performance status 0 to 2 for participants with normal hepatic function. ECOG 0 to 3 for participants with moderate or severe hepatic impairment
* Adequate organ function
* Women of childbearing potential (WOCBP)\* must agree to use a highly effective method of contraception from the time of giving informed consent until at least 10 months after the last dose of study drug. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of the first dose until at least 7 months after the last dose of study drug.

Exclusion Criteria

* Previous therapy with loncastuximab tesirine
* Allogenic or autologous stem cell transplant within 60 days prior to start of study drug (C1D1)
* Human immunodeficiency virus (HIV) seropositive
* Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load
* Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load
* History of Stevens-Johnson syndrome or toxic epidermal necrolysis
* Lymphoma with active central nervous system involvement at the time of screening, including leptomeningeal disease
* Breastfeeding or pregnant
* Significant medical comorbidities
* Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy, within 14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ADC Therapeutics S.A.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The Oncology Institute of Hope & Innovation - Lynwood

Lynwood, California, United States

Site Status COMPLETED

Hospital Sírio-Libanês - Brasília

Brasília, , Brazil

Site Status RECRUITING

Hospital Mãe de Deus - Centro Integrado de Oncologia

Porto Alegre, , Brazil

Site Status RECRUITING

Hospital Sírio-Libanês - São Paulo

São Paulo, , Brazil

Site Status RECRUITING

A Beneficência Portuguesa de São Paulo - Unidade Mirant

São Paulo, , Brazil

Site Status RECRUITING

Hospital 9 de Julho

São Paulo, , Brazil

Site Status RECRUITING

Albert Einstein Israelite Hospital

São Paulo, , Brazil

Site Status RECRUITING

Kyungpook National University Chilgok Hospital

Daegu, Daegu Gwang'yeogsi, South Korea

Site Status RECRUITING

Dong-A University Hospital

Pusan, Gyeongsangnam-do, South Korea

Site Status RECRUITING

Korea University Anam Hospital

Seoul, Seongbuk District, South Korea

Site Status ACTIVE_NOT_RECRUITING

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], South Korea

Site Status RECRUITING

Severance Hospital

Seoul, Seoul Teugbyeolsi, South Korea

Site Status RECRUITING

National Taiwan University Hospital

Taipei, , Taiwan

Site Status RECRUITING

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, , Taiwan

Site Status RECRUITING

Countries

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United States Brazil South Korea Taiwan

Central Contacts

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ADC Therapeutics

Role: CONTACT

954-903-7994

Other Identifiers

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2021-005209-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ADCT-402-107

Identifier Type: -

Identifier Source: org_study_id

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