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)

Diffuse Large B-Cell Lymphoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05660395
• Other study ID #: ADCT-402-107
• Secondary ID: 2021-005209-29
• Status: Recruiting
• Phase: Phase 1
• Start date: August 28, 2023
• Est. completion date: April 5, 2027

Study information

• Verified date: February 2024
• Source: ADC Therapeutics S.A.
• Contact: ADC Therapeutics
• Phone: 954-903-7994
• Email: clinical.trials[@]adctherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: April 5, 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Loncastuximab Tesirine
Intravenous (IV) Infusion

Locations

Country	Name	City	State
Brazil	Hospital Sírio-Libanês - Brasília	Brasília
Brazil	Hospital Mãe de Deus - Centro Integrado de Oncologia	Porto Alegre
Brazil	A Beneficência Portuguesa de São Paulo - Unidade Mirant	São Paulo
Brazil	Albert Einstein Israelite Hospital	São Paulo
Brazil	Hospital 9 de Julho	São Paulo
Brazil	Hospital Sírio-Libanês - São Paulo	São Paulo
Korea, Republic of	Dong-A University Hospital	Busan	Gyeongsangnam-do
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu	Daegu Gwang'yeogsi
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Korea, Republic of	Severance Hospital	Seoul	Seoul Teugbyeolsi
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center	Taipei
Taiwan	National Taiwan University Hospital	Taipei
United States	The Oncology Institute of Hope & Innovation - Lynwood	Lynwood	California

Sponsors (1)

Lead Sponsor	Collaborator
ADC Therapeutics S.A.

Countries where clinical trial is conducted

United States,  Brazil,  Korea, Republic of,  Taiwan, 

Outcome

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