Loncastuximab Tesirine for B-Cell Lymphoma

Overseen By Stephen Smith

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Disqualifiers: Active malignancy, Hepatitis B/C, Pregnancy, CNS involvement, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 18 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new treatment, loncastuximab tesirine, can shrink tumors in individuals with certain B-cell lymphomas (a type of blood cancer) that have returned or are difficult to treat. As a targeted therapy, it attaches to specific parts of the cancer cell and delivers a drug to kill it. The trial seeks participants whose B-cell lymphoma has returned or is unresponsive to other treatments, including those who have already tried therapies like CAR T-cell therapy or undergone a transplant. Individuals whose cancer fits these criteria and have tried at least one other treatment might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that you should not have major surgery, radiotherapy, chemotherapy, or other anti-cancer treatments within 14 days before starting the study drug, and you should not use any experimental medication within 14 days prior to starting the study.

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

Research has shown that loncastuximab tesirine has a good safety record from earlier studies. For people with hard-to-treat B-cell lymphomas, this treatment was tested and found to be safe.

Most patients experienced manageable side effects. A small number had serious side effects, such as fever with low white blood cells, pneumonia, swelling, fluid around the lungs, and infections. These serious side effects occurred in 2% or more of patients.

Overall, loncastuximab tesirine was well-tolerated by patients in previous studies. It has shown promise in treating certain types of lymphoma while keeping side effects under control. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Loncastuximab tesirine is unique because it combines an antibody with a potent chemotherapy drug, specifically targeting B-cell lymphoma cells. This targeted approach helps deliver the chemotherapy directly to the cancer cells, potentially reducing damage to healthy cells and minimizing side effects compared to traditional chemotherapy. Researchers are excited about this treatment because it offers a more precise attack on cancer cells, which could improve effectiveness and reduce the overall treatment burden for patients.

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

Research has shown that loncastuximab tesirine, the treatment under study in this trial, effectively treats B-cell lymphoma that has returned or is unresponsive to other treatments. Studies have found that it can shrink tumors in patients who have already tried several other treatments. Specifically, the LOTIS-2 study demonstrated strong results in patients with diffuse large B-cell lymphoma (DLBCL) who had few other options. This treatment targets CD19 receptors on cancer cells and delivers a chemotherapy drug directly to them, aiding in the destruction of cancer cells. Overall, evidence suggests that loncastuximab tesirine is a promising option for those with difficult-to-treat B-cell lymphoma. ^{1 2 4 6 7}

Who Is on the Research Team?

Stephen Smith

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Adults with certain B-cell malignancies that have returned or are treatment-resistant can join this trial. They must be over 18, in fairly good health (ECOG PS 0-2), and have normal-ish liver/blood tests. Specific groups include those with CD19+ lymphoma post-transplant, relapsed/refractory non-Hodgkin's excluding some types, or after CAR T-cell therapy/allogeneic transplant. Women/men of childbearing potential must agree to contraception.

Inclusion Criteria

Total bilirubin =< 1.5 x ULN (patients with known Gilbert's syndrome may have a total bilirubin up to =< 3 x ULN)

My white blood cell count is within the required range.

Negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test within 7 days prior to start of study drug (cycle 1 day 1 [C1D1]) for women of childbearing potential

Exclusion Criteria

My lymphoma affects my brain or spinal cord.

Known history of hypersensitivity to loncastuximab tesirine

I have been treated with loncastuximab tesirine before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive loncastuximab tesirine IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Loncastuximab Tesirine

Trial Overview The trial is testing Loncastuximab Tesirine for shrinking tumors in patients with B-cell malignancies that haven't responded to other treatments. It's a monoclonal antibody targeting CD19 receptors on cancer cells combined with a chemo drug to kill them.

How Is the Trial Designed?

Group I: Treatment (loncastuximab tesirine) Experimental Treatment 1 Intervention

Patients receive loncastuximab tesirine IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

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?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Published Research Related to This Trial

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]

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]

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 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]

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]

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 Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: long-term efficacy and safety from the phase II LOTIS-2 study.

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

long-term efficacy and safety from the phase II LOTIS-2 study Lonca demonstrated single-agent antitumor activity and had an acceptable safety profile in heavily pretreated patients with R/R DLBCL with an overall response ...

3. 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 ...

4. ashpublications.org ashpublications.org/blood/article/140/4/303/485279/The-antibody-drug-conjugate-loncastuximab-tesirine

The antibody-drug conjugate loncastuximab tesirine for the ... The efficacy of loncastuximab tesirine in this scenario has been validated in a small cohort of patients within the Loncastuximab Tesirine in ...

5. zynlontahcp.com zynlontahcp.com/efficacy

Efficacy | ZYNLONTA® (loncastuximab tesirine-lpyl) HCP Site Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: long-term efficacy and safety from the phase 2 LOTIS-2 study.

6. ir.adctherapeutics.com ir.adctherapeutics.com/press-releases/press-release-details/2025/ADC-Therapeutics-Announces-Updated-ZYNLONTA-Investigator-Initiated-Trial-Data-in-RR-Marginal-Zone-Lymphoma-Presented-at-18th-International-Conference-on-Malignant-Lymphoma-ICML/default.aspx

Press Release Details Updated Phase 2 data evaluating ZYNLONTA as a monotherapy demonstrate overall response rate (ORR) of 85% and complete response (CR) rate of 69%.

7. 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.