Loncastuximab Tesirine for Lymphoma

Recruiting at 13 trial locations

Overseen By ADC Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ADC Therapeutics S.A.

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

56 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that major treatments like surgery, radiotherapy, or chemotherapy should not have been done within 14 days before starting the study drug, unless approved by the Sponsor.

What data supports the effectiveness of the drug Loncastuximab Tesirine for treating lymphoma?

Loncastuximab Tesirine has been shown to be effective in treating relapsed or refractory diffuse large B-cell lymphoma, with a study reporting an overall response rate of 48.3% and a complete response rate of 24.1%. It has been approved by the US FDA for this use, based on its demonstrated safety and efficacy in clinical trials. ^{1 2 3 4 5}

Is Loncastuximab Tesirine safe for humans?

Loncastuximab Tesirine, also known as Zynlonta, has been tested in clinical trials for certain types of lymphoma and has shown a tolerable safety profile. Common side effects include low blood cell counts, liver enzyme changes, and fluid buildup, but it is generally considered safe enough for further study and use in specific lymphoma cases. ^{1 2 4 5 6}

How is the drug Loncastuximab Tesirine different from other treatments for lymphoma?

Loncastuximab Tesirine is unique because it is an antibody-drug conjugate that specifically targets CD19 on B cells, delivering a powerful cancer-killing agent directly to the cancer cells. This targeted approach helps to minimize damage to healthy cells, making it a novel option for patients with relapsed or refractory diffuse large B-cell lymphoma who have not responded to other treatments. ^{1 2 4 5 7}

What is the purpose of this trial?

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

This trial is for adults with relapsed or refractory diffuse large B-cell lymphoma or high-grade B-cell lymphoma, who've had at least one treatment. It's specifically for those with liver issues: normal function, moderate impairment (bilirubin >1.5-3x normal), or severe impairment (bilirubin >3x). Participants must be able to perform daily activities with little to some difficulty and agree to use effective contraception.

Inclusion Criteria

My liver function ranges from normal to severely impaired.

My organs are functioning well.

Measurable disease as defined by the 2014 Lugano Classification

Exclusion Criteria

I haven't had major cancer treatments in the last 14 days.

I have chronic hepatitis B and cannot or will not take standard antiviral treatments.

I have hepatitis C and have not completed treatment or still have a detectable viral load.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive loncastuximab tesirine in a dose-escalation design based on hepatic function, with cycles every 3 weeks

6 weeks

2 visits (in-person) per cycle

Dose Adjustment

Participants may have dose reductions based on toxicity, with a maximum of 2 dose reductions allowed

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Loncastuximab Tesirine

Trial Overview The study tests the drug Loncastuximab Tesirine in patients with certain types of lymphoma and varying levels of liver health. The goal is to find the safest and most effective dose for those with moderate to severe liver problems.

Participant Groups

Group I: Arm C: Severe Hepatic Impairment Experimental Treatment 1 Intervention

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.

Group II: Arm B: Moderate Hepatic Impairment Experimental Treatment 1 Intervention

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.

Group III: Arm A: Normal Hepatic Function Experimental Treatment 1 Intervention

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.

Loncastuximab Tesirine is already approved in United States, European Union for the following indications:

Approved in United States as Zynlonta for:

• Diffuse large B-cell lymphoma (DLBCL)
• DLBCL arising from low-grade lymphoma
• High-grade B-cell lymphoma

Approved in European Union as Zynlonta for:

• Diffuse large B-cell lymphoma (DLBCL)
• DLBCL arising from low-grade lymphoma
• High-grade B-cell lymphoma

Who Is Running the Clinical Trial?

ADC Therapeutics S.A.

Lead Sponsor

Trials

32

Recruited

2,700+

Findings from Research

Loncastuximab tesirine is an antibody-drug conjugate that targets B cell lymphomas, specifically approved for relapsed/refractory diffuse large B cell lymphoma (DLBCL) after two or more lines of treatment.

The drug works by using an anti-CD19 antibody to deliver a DNA-alkylating agent directly to B cells, enhancing its efficacy in targeting cancer cells while minimizing damage to healthy cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab Tesirine: First Approval. Lee, A.[2021]

Loncastuximab tesirine-lpyl, an anti-CD19 antibody-drug conjugate, has shown a 48.6% overall response rate in patients with relapsed, refractory diffuse large B-cell lymphoma, indicating its efficacy as a treatment option.

The drug has a tolerable safety profile, with common side effects including neutropenia and thrombocytopenia, leading to its recent FDA approval for treating this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma: a review of clinical data. Furqan, F., Hamadani, M.[2022]

In a phase 2 trial involving 145 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), loncastuximab tesirine demonstrated a significant overall response rate of 48.3%, indicating its effectiveness as a treatment option for this challenging patient population.

The treatment was associated with an acceptable safety profile, with serious adverse events occurring in 39% of patients, but none were directly linked to loncastuximab tesirine, suggesting it may be a safe option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Caimi, PF., Ai, W., Alderuccio, JP., et al.[2021]

Loncastuximab tesirine-lpyl, an anti-CD19 antibody drug, has been safely administered at full doses to patients with relapsed/refractory DLBCL despite their severe hepatic dysfunction, suggesting potential efficacy in this challenging patient population.

The cases presented highlight the need for further investigation into the safety and dosing guidelines of loncastuximab tesirine-lpyl in patients with moderate to severe liver impairment, as current guidance from the manufacturer is unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of loncastuximab tesirine-lpyl in diffuse large B-cell lymphoma with severe hepatic dysfunction. Baek, GT., Huang, IJ., Gopal, AK.[2023]

Loncastuximab tesirine-lpyl, an anti-CD19 antibody-drug conjugate, has shown a 48.3% overall response rate in patients with relapsed, refractory diffuse large B-cell lymphoma during the phase II LOTIS-2 trial, indicating its efficacy as a treatment option.

The drug demonstrated a tolerable safety profile with common side effects including neutropenia and thrombocytopenia, and no new safety concerns were identified in the phase II trial, suggesting it is safe for further testing in various non-Hodgkin lymphoma subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine for diffuse large B-cell lymphoma. Zurko, J., Hamadani, M.[2021]

In a phase 1 study involving 183 patients with relapsed or refractory B-cell non-Hodgkin lymphoma, loncastuximab tesirine demonstrated a promising overall response rate of 45.6%, with 26.7% achieving complete responses, indicating its potential as an effective treatment option.

The study established a recommended dose of 150 µg/kg for phase 2 trials, with an acceptable safety profile characterized by manageable hematologic toxicities, suggesting that loncastuximab tesirine could be a viable alternative to current therapies for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Hamadani, M., Radford, J., Carlo-Stella, C., et al.[2022]

In a phase II study involving 145 patients with relapsed or refractory diffuse large B-cell lymphoma, loncastuximab tesirine demonstrated significant improvements in health-related quality of life, with a notable increase in overall health scores over treatment cycles.

The treatment was well-tolerated, with over 60% of patients reporting minimal bother from side effects, indicating a favorable safety profile alongside its antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life, Symptoms, and Tolerability of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Spira, A., Zhou, X., Chen, L., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Loncastuximab Tesirine: First Approval. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma: a review of clinical data. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Safety of loncastuximab tesirine-lpyl in diffuse large B-cell lymphoma with severe hepatic dysfunction. [2023]

5. Spain pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine for diffuse large B-cell lymphoma. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life, Symptoms, and Tolerability of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [2022]