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)

NCT05660395 | Terminated Phase 1 FDA Drug

• 2 other identifiers: ADCT-402-1072021-005209-29
• Study Type: interventional
• Target: 5
• Locations: 4 countries
• Sites: 14

Brief Summary

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.

Conditions

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

Keywords

Loncastuximab Tesirine; Lymphoma; DLBCL; HGBCL; Hepatic Impairment

Outcome Measures

Primary Outcomes (1)

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

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

Secondary Outcomes (25)

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

  Day 1 up to 1 year

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

  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

  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

  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

  Day 1 up to 1 year

Study Arms (3)

Arm A: Normal Hepatic Function

EXPERIMENTAL

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.

Drug: Loncastuximab Tesirine

Arm B: Moderate Hepatic Impairment

EXPERIMENTAL

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.

Drug: Loncastuximab Tesirine

Arm C: Severe Hepatic Impairment

EXPERIMENTAL

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.

Drug: Loncastuximab Tesirine

Interventions

Loncastuximab Tesirine DRUG

Intravenous (IV) Infusion

Also known as: Zynlonta, ADCT-402

Arm A: Normal Hepatic Function; Arm B: Moderate Hepatic Impairment; Arm C: Severe Hepatic Impairment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• ADC Therapeutics S.A.: lead

Study Sites (14)

The Oncology Institute of Hope & Innovation - Lynwood

Lynwood, California, 90262, United States

Location

Hospital Sírio-Libanês - Brasília

Brasília, 70200-730, Brazil

Location

Hospital Mãe de Deus - Centro Integrado de Oncologia

Porto Alegre, 90110-270, Brazil

Location

Hospital Sírio-Libanês - São Paulo

São Paulo, 01308-050, Brazil

Location

A Beneficência Portuguesa de São Paulo - Unidade Mirant

São Paulo, 01323-030, Brazil

Location

Hospital 9 de Julho

São Paulo, 01409-002, Brazil

Location

Albert Einstein Israelite Hospital

São Paulo, 05652-900, Brazil

Location

Kyungpook National University Chilgok Hospital

Daegu, Daegu Gwang'yeogsi, 41944, South Korea

Location

Dong-A University Hospital

Pusan, Gyeongsangnam-do, 602-812, South Korea

Location

Korea University Anam Hospital

Seoul, Seongbuk District, 02841, South Korea

Location

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], 03080, South Korea

Location

Severance Hospital

Seoul, Seoul Teugbyeolsi, 03722, South Korea

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, Taiwan 112, Taiwan

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma

Interventions

loncastuximab tesirine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2022
• First Posted: December 21, 2022
• Study Start: July 28, 2023
• Primary Completion: June 25, 2026
• Study Completion: June 25, 2026
• Last Updated: July 20, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

BR (6); US (1); TW (2); KR (5)