A Study to Evaluate the Pharmacokinetics and Safety of Lo... | NCT05660395

NCT05660395

ID	Type	Description	Link
2021-005209-29	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Loncastuximab Tesirine	Drug	Intravenous (IV) Infusion	Arm A: Normal Hepatic Function Arm B: Moderate Hepatic Impairment Arm C: Severe Hepatic Impairment

Measure	Description	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

Measure	Description	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

Eligibility Module

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

ID	Term
D016403	Lymphoma, Large B-Cell, Diffuse
D008223	Lymphoma

ID	Term
D016393	Lymphoma, B-Cell
D008228	Lymphoma, Non-Hodgkin
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases