Loncastuximab Tesirine for Lymphoma

Recruiting at 17 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of loncastuximab tesirine (also known as Zynlonta or Loncastuximab Tesirine-lpyl) for individuals with certain types of lymphoma, such as diffuse large B-cell lymphoma (DLBCL), who also have liver problems. The trial examines different groups based on liver function, including normal, moderate, and severe impairment. Eligible participants have lymphoma that did not respond to treatment or recurred after treatment, along with liver issues affecting their daily lives. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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.

Is there any evidence suggesting that loncastuximab tesirine is likely to be safe for humans?

Research has shown that patients with certain types of lymphoma, specifically diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBCL), have received loncastuximab tesirine. In a safety study involving 215 people, the most common side effects included lower blood platelet levels and other lab result changes. More serious side effects, occurring in at least 2% of patients, included fever with a low white blood cell count, lung infections like pneumonia, fluid buildup in the body, and blood infections such as sepsis.

Notably, some patients with severe liver problems safely received full doses of loncastuximab tesirine. This suggests it can be used even in those with serious liver issues, although monitoring for side effects remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Loncastuximab tesirine is unique because it combines a monoclonal antibody with a cytotoxic agent to specifically target and kill cancer cells in lymphoma. Most treatments for lymphoma, like chemotherapy, attack both healthy and cancerous cells, leading to more side effects. Unlike these traditional treatments, loncastuximab tesirine aims to minimize damage to healthy cells by precisely targeting the CD19 protein on lymphoma cells. This targeted approach has the potential to improve effectiveness and reduce side effects, which is why researchers are excited about its potential.

What evidence suggests that loncastuximab tesirine might be an effective treatment for lymphoma?

Research has shown that loncastuximab tesirine, also known as ZYNLONTA®, offers promising results for treating diffuse large B-cell lymphoma (DLBCL). In one study, it proved effective for many patients who had already tried other treatments. Specifically, 48.3% of the patients responded well to the treatment. Some experienced long-lasting benefits, with effects lasting over a year. Most side effects were manageable, meaning they weren't too severe for most people. This trial will evaluate loncastuximab tesirine across different treatment arms based on hepatic function, suggesting it could be a valuable option for those with difficult-to-treat lymphoma. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37646659/

long-term efficacy and safety from the phase II LOTIS-2 study Lonca continued to demonstrate durable, long-term responses with manageable safety and tolerability in patients with CR.

2. zynlonta.com zynlonta.com/study-results/

Study Results | ZYNLONTA® (loncastuximab tesirine-lpyl ... ZYNLONTA® was effective for many people who had past R/R DLBCL therapies. The ZYNLONTA® clinical trial included people who had already received a variety of ...

3. haematologica.org haematologica.org/article/view/haematol.2023.283459

long-term efficacy and safety from the phase II LOTIS-2 study Durable responses to Lonca were observed, with a median duration of response (DOR) of 13.4 months and a median DOR in patients with CR not ...

4. ir.adctherapeutics.com ir.adctherapeutics.com/press-releases/press-release-details/2025/ADC-Therapeutics-Announces-Updated-Data-from-LOTIS-7-Clinical-Trial-Presented-at-the-European-Hematology-Association-2025-Congress/default.aspx

ADC Therapeutics Announces Updated Data from LOTIS-7 ... The presentation highlights updated data as of April 14, 2025, in which r/r LBCL patients received dose levels of 120 µg/kg or 150 µg/kg of ...

5. ashpublications.org ashpublications.org/bloodadvances/article/8/1/93/498392/Clinical-outcomes-of-older-and-younger-patients

Clinical outcomes of older and younger patients treated with ... The pivotal LOTIS-2 study demonstrated an overall response rate (ORR) of 48.3% with durable responses in a heavily pretreated, difficult-to- ...

6. zynlontahcp.com zynlontahcp.com/safety

Safety Profile - loncastuximab tesirine-lpyl (ZYNLONTA The most common serious adverse reactions that occurred in ≥2% of patients were febrile neutropenia, pneumonia, edema, pleural effusion, and sepsis.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/761196s000lbl.pdf

loncastuximab tesirine-lpyl - accessdata.fda.gov In this pooled safety population of 215 patients, the most common (>20%) adverse reactions, including laboratory abnormalities, were thrombocytopenia, increased ...

8. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.34816

Safety of loncastuximab tesirine‐lpyl in diffuse large B‐cell ... The authors present two cases of r/r DLBCL safely treated with full-dose loncastuximab tesirine-lpyl in the setting of severe hepatic dysfunction.

9. ncoda.org ncoda.org/wp-content/uploads/2025/03/Loncastuximab-tesirine-lpyl-Zynlonta-in-Relapsed-Refractory-Large-B-Cell-Lymphoma_PQI_NCODA.pdf

Loncastuximab tesirine-lpyl (Zynlonta®) in Relapsed/ ... PQI Process: Use of loncastuximab tesirine-lpyl should include the following safety considerations. • Verification of dosage, schedule, and ...

10. mayoclinic.org mayoclinic.org/drugs-supplements/loncastuximab-tesirine-lpyl-intravenous-route/description/drg-20514884

Loncastuximab tesirine-lpyl (intravenous route) Loncastuximab tesirine-lpyl injection is to treat large B-cell lymphoma ... Safety and efficacy have not been established. Geriatric.