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

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment called loncastuximab tesirine for patients whose B-cell cancers have returned or don't respond to other treatments. The treatment uses a special protein to find cancer cells and deliver a chemotherapy drug directly to them. Patients receive this treatment periodically and are monitored for several years after treatment. Loncastuximab tesirine has been previously tested in an earlier study for similar conditions.

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.

What data supports the effectiveness of the drug Loncastuximab Tesirine for B-Cell Lymphoma?

Loncastuximab Tesirine has been shown to be effective in treating relapsed or refractory diffuse large B-cell lymphoma, with a study showing 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, and ongoing trials are evaluating its safety and effectiveness in other types of non-Hodgkin lymphoma. ^{1 2 3 4 5}

What is known about the safety of Loncastuximab Tesirine for B-Cell Lymphoma?

Loncastuximab Tesirine has been shown to have a tolerable safety profile in clinical trials for B-cell lymphomas, with common side effects including low white blood cell counts (neutropenia), low platelet counts (thrombocytopenia), and elevated liver enzymes. It has been safely used in patients with severe liver dysfunction, although specific dose adjustments are not clearly defined. ^{1 2 3 4 5}

What makes the drug Loncastuximab Tesirine unique for treating B-cell lymphoma?

Loncastuximab Tesirine is unique because it is an antibody-drug conjugate that specifically targets CD19 on B cells, delivering a potent toxin 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 3 5 6}

Research Team

Stephen Smith

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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.

I am 18 years old or older.

Exclusion Criteria

My lymphoma affects my brain or spinal cord.

I have been treated with loncastuximab tesirine before.

Known history of hypersensitivity to loncastuximab tesirine

Timeline

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

Treatment Details

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.

Participant Groups

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+

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 48.3% 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, 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]

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 48.6% 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 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]

References

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

Loncastuximab Tesirine: First Approval. [2021]

2. Spain pubmed.ncbi.nlm.nih.gov

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

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

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

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

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

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]