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)

ADC Therapeutics

Status and phase: Enrolling; Phase 1

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

Treatments: Drug: Loncastuximab Tesirine

Study type: Interventional

Funder types: Industry

Identifiers

NCT05660395

ADCT-402-107

2021-005209-29 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 56 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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56 participants in 3 patient groups

Arm A: Normal Hepatic Function

Experimental group

Description:

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.

Treatment:

Drug: Loncastuximab Tesirine

Arm B: Moderate Hepatic Impairment

Experimental group

Description:

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.

Treatment:

Drug: Loncastuximab Tesirine

Arm C: Severe Hepatic Impairment

Experimental group

Description:

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.

Treatment:

Drug: Loncastuximab Tesirine