Clinical trial NCT05660395: 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)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Diffuse Large B-Cell Lymphoma
High-grade B-cell Lymphoma
Keywords: Loncastuximab Tesirine
Lymphoma
DLBCL
HGBCL
Hepatic Impairment
Lead sponsor: ADC Therapeutics S.A.
Sponsor class: INDUSTRY
First posted: 2022-12-21
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with Moderate or Severe Hepatic Impairment Who Experience a Dose-Limiting Toxicity (DLT)
timeFrame: Day 1 to Day 21 of Cycle 1, where a cycle is 21 days
Secondary outcomes:
measure: Maximum Concentration (Cmax) of Loncastuximab Tesirine and SG3199 in Serum
timeFrame: Day 1 up to 1 year
measure: Time to Cmax (Tmax) of Loncastuximab Tesirine and SG3199 in Serum
timeFrame: Day 1 up to 1 year
measure: Area Under the Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine and SG3199 in Serum
timeFrame: Day 1 up to 1 year
measure: Area Under the Concentration-time Curve from Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine and SG3199 in Serum
timeFrame: Day 1 up to 1 year
measure: Area Under the Concentration-time Curve from Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine and SG3199 in Serum
timeFrame: Day 1 up to 1 year
measure: Apparent Terminal Elimination Half-life (Thalf) of Loncastuximab Tesirine and SG3199 in Serum
timeFrame: Day 1 up to 1 year
measure: Apparent Clearance (CL) of Loncastuximab Tesirine and SG3199 in Serum
timeFrame: Day 1 up to 1 year
measure: Apparent Steady-state Volume of Distribution (Vss) of Loncastuximab Tesirine and SG3199 in Serum
timeFrame: Day 1 up to 1 year
measure: Accumulation Index (AI) of Loncastuximab Tesirine and SG3199 in Serum
timeFrame: Day 1 up to 1 year
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to approximately 3 years
measure: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
timeFrame: Up to approximately 1 year
measure: Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Delay
timeFrame: Up to approximately 1 year
measure: Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Interruption
timeFrame: Up to approximately 1 year
measure: Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Reduction
timeFrame: Up to approximately 1 year
measure: Number of Participants Who Experience a Clinically Significant Change from Baseline in Safety Laboratory Values
timeFrame: Baseline up to approximately 1 year
measure: Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Signs
timeFrame: Baseline up to approximately 1 year
measure: Number of Participants Who Experience a Clinically Significant Change from Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: Baseline up to approximately 1 year
measure: Number of Participants Who Experience a Clinically Significant Change from Baseline in 12-Lead Electrocardiogram (ECG) Measurements
timeFrame: Baseline up to approximately 1 year
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 3 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 3 years
measure: Complete Response (CR) Rate
timeFrame: Up to approximately 3 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 3 years
measure: Relapse-Free Survival (RFS)
timeFrame: Up to approximately 3 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 3 years
measure: Number of Participants With Anti-drug Antibody (ADA) Titers to Loncastuximab Tesirine
timeFrame: Day 1 up to 1 year
Other outcomes:
Locations:
city: Lynwood
country: United States
facility: The Oncology Institute of Hope & Innovation - Lynwood
state: California
city: Brasília
country: Brazil
facility: Hospital Sírio-Libanês - Brasília
city: Porto Alegre
country: Brazil
facility: Hospital Mãe de Deus - Centro Integrado de Oncologia
city: São Paulo
country: Brazil
facility: Hospital Sírio-Libanês - São Paulo
city: São Paulo
country: Brazil
facility: A Beneficência Portuguesa de São Paulo - Unidade Mirant
city: São Paulo
country: Brazil
facility: Hospital 9 de Julho
city: São Paulo
country: Brazil
facility: Albert Einstein Israelite Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
state: Daegu Gwang'yeogsi
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
state: Gyeongsangnam-do
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
state: Seongbuk District
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
state: Seoul Teugbyeolsi
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center
Study officials:
References: