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)

Phase 1RecruitingNCT05660395

ADC Therapeutics S.A.56 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

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

Interventions

Loncastuximab Tesirine

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (14)

The Oncology Institute of Hope & Innovation - Lynwood

Lynwood, California, United States

COMPLETED

Hospital Sírio-Libanês - Brasília

Brasília, Brazil

RECRUITING

Hospital Mãe de Deus - Centro Integrado de Oncologia

Porto Alegre, Brazil

RECRUITING

Hospital Sírio-Libanês - São Paulo

São Paulo, Brazil

RECRUITING

A Beneficência Portuguesa de São Paulo - Unidade Mirant

São Paulo, Brazil

RECRUITING

Hospital 9 de Julho

São Paulo, Brazil

RECRUITING

Albert Einstein Israelite Hospital

São Paulo, Brazil

RECRUITING

Kyungpook National University Chilgok Hospital

Daegu, Daegu Gwang'yeogsi, South Korea

RECRUITING

Dong-A University Hospital

Pusan, Gyeongsangnam-do, South Korea

RECRUITING

Korea University Anam Hospital

Seoul, Seongbuk District, South Korea

ACTIVE_NOT_RECRUITING

...and 4 more locations

Outcomes

Primary Outcomes

Number of Participants with Moderate or Severe Hepatic Impairment Who Experience a Dose-Limiting Toxicity (DLT)

Time frame: Day 1 to Day 21 of Cycle 1, where a cycle is 21 days

Secondary Outcomes

Maximum Concentration (Cmax) of Loncastuximab Tesirine and SG3199 in Serum

Time frame: Day 1 up to 1 year

Time to Cmax (Tmax) of Loncastuximab Tesirine and SG3199 in Serum

Time frame: Day 1 up to 1 year

Area Under the Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine and SG3199 in Serum

Time frame: Day 1 up to 1 year

Area Under the Concentration-time Curve from Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine and SG3199 in Serum

Time frame: Day 1 up to 1 year

Area Under the Concentration-time Curve from Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine and SG3199 in Serum

Time frame: Day 1 up to 1 year

Apparent Terminal Elimination Half-life (Thalf) of Loncastuximab Tesirine and SG3199 in Serum

Time frame: Day 1 up to 1 year

Apparent Clearance (CL) of Loncastuximab Tesirine and SG3199 in Serum

Time frame: Day 1 up to 1 year

Apparent Steady-state Volume of Distribution (Vss) of Loncastuximab Tesirine and SG3199 in Serum

Time frame: Day 1 up to 1 year

Accumulation Index (AI) of Loncastuximab Tesirine and SG3199 in Serum

Time frame: Day 1 up to 1 year

Number of Participants Who Experience an Adverse Event (AE)

Time frame: Up to approximately 3 years

Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)

Time frame: Up to approximately 1 year

Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Delay

Time frame: Up to approximately 1 year

Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Interruption

Time frame: Up to approximately 1 year

Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Reduction

Time frame: Up to approximately 1 year

Number of Participants Who Experience a Clinically Significant Change from Baseline in Safety Laboratory Values

Time frame: Baseline up to approximately 1 year

Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Signs

Time frame: Baseline up to approximately 1 year

Number of Participants Who Experience a Clinically Significant Change from Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status

Time frame: Baseline up to approximately 1 year

Number of Participants Who Experience a Clinically Significant Change from Baseline in 12-Lead Electrocardiogram (ECG) Measurements

Time frame: Baseline up to approximately 1 year

Overall Response Rate (ORR)

Time frame: Up to approximately 3 years

Duration of Response (DOR)

Time frame: Up to approximately 3 years

Complete Response (CR) Rate

Time frame: Up to approximately 3 years

Progression-Free Survival (PFS)

Time frame: Up to approximately 3 years

Relapse-Free Survival (RFS)

Time frame: Up to approximately 3 years

Overall Survival (OS)

Time frame: Up to approximately 3 years

Number of Participants With Anti-drug Antibody (ADA) Titers to Loncastuximab Tesirine

Time frame: Day 1 up to 1 year

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)

Overview

Conditions

Interventions

Eligibility

Locations (14)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts