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 tests a treatment called loncastuximab tesirine (an antibody-drug conjugate) to determine its effects on people with marginal zone lymphoma, a type of immune cell cancer. The trial aims to identify both the positive and negative effects of this treatment. Participants will receive the treatment for about 4.5 months, with doses administered every three weeks. Suitable candidates for this trial have marginal zone lymphoma that has not responded to previous treatments and exhibit symptoms such as large lymph node swelling, weight loss, or night sweats related to their condition. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

Research has shown that loncastuximab tesirine has been tested in patients with immune cell cancers, yielding promising results. In one study, 85% of patients experienced some improvement in their condition. The safety of this treatment remains manageable.

The most common serious side effects, affecting more than 2% of patients, include fever with a low white blood cell count, pneumonia, swelling, fluid around the lungs, and severe infection. Despite these side effects, patients generally tolerate the treatment well. Previous patients have experienced long-term positive responses, suggesting that the benefits might outweigh the risks for many. ^{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 powerful chemotherapy agent, specifically targeting and attacking cancer cells in marginal zone lymphoma. Unlike traditional treatments like rituximab or chemotherapy alone, which may affect healthy cells, this drug delivers its cytotoxic payload directly to the cancer cells, potentially reducing side effects. Researchers are excited about this approach as it offers a targeted attack on lymphoma cells, which could lead to more effective treatments with fewer unwanted side effects.

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

Research shows that loncastuximab tesirine, which participants in this trial will receive, looks promising for treating marginal zone lymphoma. In earlier studies, this treatment achieved an overall response rate of 85%, with most patients experiencing cancer shrinkage or disappearance. Impressively, 69% of patients had a complete response, with no detectable cancer after treatment. The treatment has also demonstrated lasting effects, with benefits continuing over time. These findings suggest that loncastuximab tesirine could be an effective option for people with this type of lymphoma. ^{1 2 4 5 6}

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

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]

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]

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 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 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]

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]

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]

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]

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]

Citations

1. 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%.

2. onclive.com onclive.com/view/loncastuximab-tesirine-elicits-responses-in-r-r-marginal-zone-lymphoma

Loncastuximab Tesirine Elicits Responses in R/R Marginal ... Treatment with loncastuximab tesirine yielded high response rates in patients with relapsed or refractory marginal zone lymphoma.

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. 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.

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2021/761196Orig1s000MultidisciplineR.pdf

761196Orig1s000 - accessdata.fda.gov ... trial to verify and describe the clinical benefit of loncastuximab tesirine‐lpyl in patients with relapsed or refractory large B‐cell lymphoma. The trial ...

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.