Loncastuximab Tesirine for Marginal Zone Lymphoma

Recruiting at 3 trial locations

Overseen By Philip Arlen, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Miami

Must be taking: Anti-CD20 antibodies

Must not be taking: Anticancer drugs, Steroids

Disqualifiers: DLBCL, CNS lymphoma, HIV, 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: 6

Duration: 18 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a medication called loncastuximab tesirine in patients with immune cell cancers. The medication works by finding and sticking to cancer cells, then releasing a poison to kill them. Researchers want to see if this treatment is effective and safe for these patients. Loncastuximab tesirine is a recently approved treatment for a type of immune cell cancer that has returned or not responded to previous treatments.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving anticancer therapy or have taken certain anticancer medications or investigational drugs within specific time frames before the trial starts. It's best to discuss your current medications with the trial team.

Is Loncastuximab Tesirine safe for humans?

Loncastuximab Tesirine, also known as Zynlonta, has been shown to have a tolerable safety profile in clinical trials for diffuse large B-cell lymphoma, with common side effects including low white blood cell counts, low platelet counts, and elevated liver enzymes. It has been safely used even in patients with severe liver issues, but always consult with a healthcare provider for personal medical advice. ^{1 2 3 4 5}

What makes the drug Loncastuximab Tesirine unique for treating marginal zone lymphoma?

Loncastuximab Tesirine is unique because it is an antibody-drug conjugate, which means it combines an antibody that specifically targets cancer cells with a powerful chemotherapy drug, allowing for direct delivery to the cancer cells and potentially reducing damage to healthy cells. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Loncastuximab Tesirine for treating Marginal Zone Lymphoma?

Loncastuximab Tesirine has shown effectiveness in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with a response rate of about 48% in clinical trials. While it is not specifically approved for Marginal Zone Lymphoma, its success in similar B-cell lymphomas suggests potential effectiveness. ^{1 2 3 4 11}

Who Is on the Research Team?

Izidore Lossos, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Marginal Zone Lymphoma who've had at least one prior systemic therapy including an anti-CD20 antibody. They should have measurable disease or specific criteria met for non-measurable disease, and be able to undergo biopsies if needed. Key exclusions include recent cancer treatments, other malignancies within the last 3 years, certain heart conditions, liver cirrhosis, autoimmune disorders requiring strong immunosuppression, active infections or HIV/HBV/HCV infection.

Inclusion Criteria

I've had treatment including an anti-CD20 antibody for my condition but it didn't fully work.

I have a conjunctival eye lesion that is at least 1 cm wide or I have multiple lesions.

I meet one of the required criteria to start treatment.

Exclusion Criteria

Pregnancy or breastfeeding

Conditions interfering with study participation or interpretation of data

I am unable to make my own medical decisions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients will be treated with loncastuximab tesirine for a total of 6 cycles on Day 1 (+/-3) of each 21 day (3 week) cycle

18 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Loncastuximab Tesirine

Trial Overview The study tests two doses of Loncastuximab tesirine (150 µg/Kg and 75µg/Kg) in patients with relapsed/refractory Marginal Zone Lymphoma to evaluate its effectiveness and safety. It's an open-label trial meaning everyone knows which treatment they're getting.

How Is the Trial Designed?

Group I: Loncastuximab tesirine Cycles 1-6 Experimental Treatment 2 Interventions

Patients will be treated with loncastuximab tesirine for a total of 6 cycles on Day 1 (+/-3) of each 21 day (3 week) cycle. The total duration of treatment is approximately 18 weeks (4.5 months)

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 Miami

Lead Sponsor

Trials

976

Recruited

423,000+

ADC Therapeutics S.A.

Industry Sponsor

Trials

32

Recruited

2,700+

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, an antibody-drug conjugate targeting CD19, has shown promising efficacy in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with overall response rates of 42.3% in LOTIS-1 and 48.3% in LOTIS-2 trials.

The treatment has an acceptable safety profile, with common side effects including anemia, neutropenia, fatigue, and nausea, making it a viable option for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma. Xu, B.[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 48.6% 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 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, 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]

Novel agents like lenalidomide, bortezomib, and 90yttrium-ibrutumomab tiuxetan have shown efficacy in treating marginal zone lymphoma, based on trials specifically designed for this patient group.

Targeted therapies such as obinutuzumab, ibrutinib, and idelalisib, along with newer drugs like venetoclax and copanlisib, are being explored for their safety and effectiveness, indicating a promising direction for treatment in indolent non-Hodgkin's lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible novel agents in marginal zone lymphoma. Zinzani, PL., Broccoli, A.[2021]

Marginal zone lymphoma (MZL) is often overlooked in clinical trials that focus on other types of indolent lymphomas, highlighting the need for more targeted research.

The study suggests that disease progression within 24 months is linked to worse outcomes in MZL patients, indicating that future research should evaluate the effectiveness of new treatments specifically for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A roadmap for clinical trial design in marginal zone lymphoma. Alderuccio, JP., Habermann, T., Kuker, R., et al.[2023]

In a study of 183 advanced marginal zone lymphoma patients, the combination of rituximab and cladribine (R-2CdA) showed comparable efficacy to the standard treatment of rituximab plus R-CHOP, with overall response rates of 84.6% for R-2CdA and 94.9% for R-CHOP.

R-2CdA was found to be safer than R-CHOP, with significantly lower rates of severe hematological adverse events, suggesting it may be a preferable first-line therapy option for advanced-stage MZL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab plus cladribine versus R-CHOP in frontline management of marginal zone lymphoma in China: a propensity-score matched multicenter study. Wang, Y., Xu, J., Li, J., et al.[2022]

In a study of 175 patients with marginal zone B-cell lymphoma (MZL), rituximab-bendamustine was the most commonly used treatment, showing an overall response rate of 81% across different MZL subtypes.

Five-year progression-free survival rates were 69% for MALT MZL and 66% for non-MALT MZL, indicating that both subtypes respond well to treatment, although non-MALT patients often present with more advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rare lymphomas in routine practice - Treatment and outcome in marginal zone lymphoma in the prospective German Tumour Registry Lymphatic Neoplasms. Knauf, W., Abenhardt, W., Koenigsmann, M., et al.[2021]

Marginal zone lymphoma (MZL) is a diverse group of indolent non-Hodgkin lymphomas with three distinct subtypes, each requiring tailored therapeutic approaches due to their unique biology and clinical presentations.

Recent advancements in treatment options, including novel agents with improved efficacy and safety, highlight the need for more specific clinical trials and the development of prognostic biomarkers to better guide therapy for MZL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Treatments in Marginal Zone Lymphoma. Alderuccio, JP., Kahl, BS.[2022]

Citations

1. Spain pubmed.ncbi.nlm.nih.gov

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

2. Germany pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma. [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. England pubmed.ncbi.nlm.nih.gov

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

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

Loncastuximab Tesirine: First Approval. [2021]

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

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

Possible novel agents in marginal zone lymphoma. [2021]

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

A roadmap for clinical trial design in marginal zone lymphoma. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Rituximab plus cladribine versus R-CHOP in frontline management of marginal zone lymphoma in China: a propensity-score matched multicenter study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Rare lymphomas in routine practice - Treatment and outcome in marginal zone lymphoma in the prospective German Tumour Registry Lymphatic Neoplasms. [2021]

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

Current Treatments in Marginal Zone Lymphoma. [2022]