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)

A Phase 1b Open-Label Study to Evaluate the Pharmacokinetics and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma or High-grade B-cell Lymphoma With Hepatic Impairment (LOTIS-10)

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 Overview

• Status: Recruiting
• Conditions: Diffuse Large B-Cell Lymphoma; High-grade B-cell Lymphoma
• Intervention / Treatment: Drug: Loncastuximab Tesirine

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: ADC Therapeutics; Phone Number: 954-903-7994; Email: clinical.trials@adctherapeutics.com

Study Locations

• Brazil
  • Brasília, Brazil, 70200-730
    • Recruiting
    • Hospital Sírio-Libanês - Brasília
  • Porto Alegre, Brazil, 90110-270
    • Recruiting
    • Hospital Mãe de Deus - Centro Integrado de Oncologia
  • São Paulo, Brazil, 01308-050
    • Recruiting
    • Hospital Sírio-Libanês - São Paulo
  • São Paulo, Brazil, 01323-030
    • Recruiting
    • A Beneficência Portuguesa de São Paulo - Unidade Mirant
  • São Paulo, Brazil, 01409-002
    • Recruiting
    • Hospital 9 de Julho
  • São Paulo, Brazil, 05652-900
    • Recruiting
    • Albert Einstein Israelite Hospital
• Korea, Republic of
  • Daegu Gwang'yeogsi
    • Daegu, Daegu Gwang'yeogsi, Korea, Republic of, 41944
      • Recruiting
      • Kyungpook National University Chilgok Hospital
  • Gyeongsangnam-do
    • Busan, Gyeongsangnam-do, Korea, Republic of, 602-812
      • Recruiting
      • Dong-A University Hospital
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
      • Recruiting
      • Severance Hospital
  • Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
    • Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], Korea, Republic of, 03080
      • Recruiting
      • Seoul National University Hospital
• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
  • Taipei, Taiwan, Taiwan 112
    • Recruiting
    • Koo Foundation Sun Yat-Sen Cancer Center
• United States
  • California
    • Lynwood, California, United States, 90262
      • Recruiting
      • The Oncology Institute of Hope & Innovation - Lynwood

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Loncastuximab Tesirine; Intravenous (IV) Infusion; Other Names: Zynlonta; ADCT-402
Experimental: 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.	Drug: Loncastuximab Tesirine; Intravenous (IV) Infusion; Other Names: Zynlonta; ADCT-402
Experimental: 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.	Drug: Loncastuximab Tesirine; Intravenous (IV) Infusion; Other Names: Zynlonta; ADCT-402

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Apparent Terminal Elimination Half-life (Thalf) of Loncastuximab Tesirine and SG3199 in Serum	Day 1 up to 1 year
Apparent Clearance (CL) of Loncastuximab Tesirine and SG3199 in Serum	Day 1 up to 1 year
Apparent Steady-state Volume of Distribution (Vss) of Loncastuximab Tesirine and SG3199 in Serum	Day 1 up to 1 year
Accumulation Index (AI) of Loncastuximab Tesirine and SG3199 in Serum	Day 1 up to 1 year
Number of Participants Who Experience an Adverse Event (AE)	Up to approximately 3 years
Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)	Up to approximately 1 year
Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Delay	Up to approximately 1 year
Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Interruption	Up to approximately 1 year
Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Reduction	Up to approximately 1 year
Number of Participants Who Experience a Clinically Significant Change from Baseline in Safety Laboratory Values	Baseline up to approximately 1 year
Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Signs	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	Baseline up to approximately 1 year
Number of Participants Who Experience a Clinically Significant Change from Baseline in 12-Lead Electrocardiogram (ECG) Measurements	Baseline up to approximately 1 year
Overall Response Rate (ORR)	Up to approximately 3 years
Duration of Response (DOR)	Up to approximately 3 years
Complete Response (CR) Rate	Up to approximately 3 years
Progression-Free Survival (PFS)	Up to approximately 3 years
Relapse-Free Survival (RFS)	Up to approximately 3 years
Overall Survival (OS)	Up to approximately 3 years
Number of Participants With Anti-drug Antibody (ADA) Titers to Loncastuximab Tesirine	Day 1 up to 1 year

Collaborators and Investigators

• Sponsor: ADC Therapeutics S.A.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): April 5, 2027

Study Registration Dates

• First Submitted: December 13, 2022
• First Submitted That Met QC Criteria: December 13, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: DLBCL; Lymphoma; Hepatic Impairment; Loncastuximab Tesirine; HGBCL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Antineoplastic Agents; Antineoplastic Agents, Immunological; Loncastuximab tesirine
• Other Study ID Numbers: ADCT-402-107; 2021-005209-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No