Loncastuximab Tesirine + Rituximab for Lymphoma

(LOTIS 5 Trial)

Recruiting at 147 trial locations

Overseen By ADC Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ADC Therapeutics S.A.

Must not be taking: Antiretrovirals, Antivirals, Immunosuppressants, others

Disqualifiers: Burkitt lymphoma, Active malignancy, Autoimmune, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

440 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy of loncastuximab tesirine (ADCT-402) combined with rituximab compared to standard immunochemotherapy.

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 have had radiotherapy, chemotherapy, or other antineoplastic therapy within 14 days before starting the study drug, and you must not use any other experimental medication within 14 days or 5 half-lives before starting the study drug. It's best to discuss your current medications with the trial team.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not have had radiotherapy, chemotherapy, or other antineoplastic therapy within 14 days before starting the study drug, unless approved by the Sponsor.

What data supports the idea that Loncastuximab Tesirine + Rituximab for Lymphoma is an effective treatment?

The available research shows that Rituximab, when combined with chemotherapy, has significantly improved outcomes for patients with certain types of lymphoma, such as follicular lymphoma and diffuse large B-cell lymphoma. It has been shown to increase the time patients live without the disease getting worse and improve overall survival rates. Although the specific combination of Loncastuximab Tesirine and Rituximab is not directly discussed, Rituximab's effectiveness in combination with other treatments suggests potential benefits. Compared to other treatments, Rituximab is often considered a standard part of therapy for these conditions due to its proven benefits. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination Loncastuximab Tesirine and Rituximab for lymphoma?

Rituximab, one of the drugs in the combination, has been shown to improve survival rates and treatment outcomes in various types of lymphoma, such as follicular lymphoma and diffuse large B-cell lymphoma, when used with chemotherapy. This suggests that Rituximab is effective in treating certain lymphomas, which may support its use in combination with Loncastuximab Tesirine. ^{1 2 3 4 5}

What safety data is available for Loncastuximab Tesirine and Rituximab in lymphoma treatment?

The safety of rituximab and its biosimilars, such as CT-P10 and Zytux™, has been evaluated in various studies. These studies indicate that rituximab biosimilars have comparable safety profiles to the original rituximab (MabThera). Adverse events are common but generally manageable, with serious treatment-related events being less frequent. Switching between rituximab biosimilars does not appear to introduce additional safety risks. Additionally, late-onset neutropenia is a known adverse effect of rituximab therapy. However, specific safety data for Loncastuximab Tesirine in combination with rituximab is not detailed in the provided research. ^{6 7 8 9 10}

Is the combination of Loncastuximab Tesirine and Rituximab generally safe for humans?

Rituximab and its biosimilars have been studied for safety in various conditions, including lymphoma and leukemia. Most patients experience some side effects, but serious reactions are rare. The safety of switching between different rituximab products has also been confirmed, with no new safety concerns identified. ^{6 7 8 9 10}

Is the drug Loncastuximab Tesirine and Rituximab a promising treatment for lymphoma?

Yes, the combination of Loncastuximab Tesirine and Rituximab is promising for treating lymphoma. Rituximab has been shown to improve survival rates and outcomes in various types of lymphoma, including follicular and diffuse large B-cell lymphoma, when used with other treatments. It is considered a valuable and effective therapy in these cases. ^{2 3 8 11 12}

What makes the drug Loncastuximab Tesirine + Rituximab unique for treating lymphoma?

Loncastuximab Tesirine + Rituximab is unique because it combines a targeted therapy (Loncastuximab Tesirine) with Rituximab, a well-established monoclonal antibody, potentially offering a novel approach to treating lymphoma by targeting cancer cells more precisely and effectively than traditional chemotherapy alone. ^{2 3 8 11 12}

Eligibility Criteria

Adults with Diffuse Large B-Cell Lymphoma who have relapsed or didn't respond to previous treatments can join. They must be in good enough health for the trial, not planning a stem cell transplant, and agree to use effective contraception. People can't join if they're pregnant/breastfeeding, recently used experimental drugs/vaccines, had certain recent treatments including loncastuximab tesirine or R-GemOx, have uncontrolled diseases like HIV/HBV/HCV or severe heart conditions.

Inclusion Criteria

Measurable disease as defined by the 2014 Lugano Classification

My diagnosis is DLBCL or high-grade B-cell lymphoma with specific gene rearrangements.

My condition did not improve after receiving a combination of treatments.

Exclusion Criteria

I have been diagnosed with Burkitt lymphoma.

Any other significant medical illness, abnormality, or condition

History of Stevens-Johnson syndrome or toxic epidermal necrolysis

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Loncastuximab Tesirine combined with Rituximab or standard immunochemotherapy for up to 8 cycles

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Loncastuximab Tesirine
• Rituximab

Trial Overview The study is testing whether combining Loncastuximab Tesirine with Rituximab is more effective than standard immunochemotherapy for treating Diffuse Large B-Cell Lymphoma. Participants will either receive this new combination therapy or the usual treatment involving Gemcitabine and Oxaliplatin.

Participant Groups

Group I: Part 2: Loncastuximab Tesirine + Rituximab (Lonca-R) Experimental Treatment 2 Interventions

Randomized participants will receive Lonca-R on Day 1 of each cycle for up to 8 cycles, where 1 cycle is 3 weeks. Lonca-R will be administered via an intravenous infusion of loncastuximab tesirine 150 µg/kg + rituximab 375 mg/m\^2 every Q3W for 2 cycles, then loncastuximab tesirine 75 µg/kg + rituximab 375 mg/m\^2 Q3W for up to 6 additional cycles.

Group II: Part 1: Loncastuximab Tesirine + Rituximab (Lonca-R) Experimental Treatment 2 Interventions

Part 1 consists of a non-randomized safety run-in period evaluating the study drug for the first 20 participants. Participants will receive Lonca-R on Day 1 of each cycle for up to 8 cycles, where 1 cycle is 3 weeks. Lonca-R will be administered via an intravenous infusion of loncastuximab tesirine 150 µg/kg + rituximab 375 mg/m\^2 Q3W for 2 cycles, then loncastuximab tesirine 75 µg/kg + rituximab 375 mg/m\^2 Q3W for up to 6 additional cycles.

Group III: Part 2: Standard Immunochemotherapy (R-GemOx) Active Control 3 Interventions

Randomized participants will receive R-GemOx consisting of rituximab, gemcitabine and oxaliplatin as a standard immunochemotherapy treatment on Day 1 or Day 2 of each cycle for up to 8 cycles, where 1 Cycle is 2 weeks. R-GemOx will be administered via an intravenous infusion of rituximab 375 mg/m\^2 + gemcitabine 1000 mg/m\^2 + oxaliplatin 100 mg/m\^2 every 2 weeks (Q2W) for up to 8 cycles.

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+

Findings from Research

Rituximab, a monoclonal antibody, has significantly improved survival rates for patients with follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) when used in combination with chemotherapy.

In patients with chronic lymphocytic leukaemia (CLL), rituximab-based chemoimmunotherapy has led to higher complete response and progression-free survival rates, demonstrating its efficacy in both untreated and relapsed cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab for the treatment of non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. Hagemeister, F.[2021]

Rituximab significantly improves progression-free survival in patients with chronic lymphocytic leukemia (CLL) and follicular lymphoma when combined with chemotherapy, based on results from multiple randomized trials involving various treatment regimens.

The drug is generally well tolerated, with infusion reactions being the most common side effect, and it is considered cost-effective for treating certain types of lymphoma, reinforcing its status as a standard care option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on rituximab in chronic lymphocytic leukemia, low-grade or follicular lymphoma, and diffuse large B-cell lymphoma. Keating, GM.[2017]

Rituximab significantly improves progression-free survival in patients with chronic lymphocytic leukaemia (CLL) and follicular lymphoma when combined with chemotherapy, based on results from multiple randomized trials.

The treatment is generally well tolerated, with infusion reactions being the most common side effect, and it is considered cost-effective for various lymphoma types, reinforcing its status as a standard care option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: a review of its use in chronic lymphocytic leukaemia, low-grade or follicular lymphoma and diffuse large B-cell lymphoma. Keating, GM.[2021]

The review analyzed 56 studies on anti-CD20 monoclonal antibodies combined with chemotherapy for treating relapsed or refractory B-cell malignancies, including chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL), highlighting a significant focus on rituximab due to the larger amount of available data.

Despite the promising potential of these combination regimens, the evidence remains inconclusive regarding the efficacy differences among the anti-CD20 agents, underscoring the need for more direct comparative studies to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Evidence-based Review of Anti-CD20 Antibody-containing Regimens for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Diffuse Large B-cell Lymphoma, or Follicular Lymphoma. Falchi, L., Ferrajoli, A., Jacobs, I., et al.[2019]

In a phase II study involving 54 patients with aggressive B-cell lymphomas, rituximab demonstrated significant clinical activity, achieving an overall response rate of 31%, with complete responses in 9% and partial responses in 22% of patients.

The treatment was well-tolerated, with mild adverse events primarily related to infusion syndrome, indicating that rituximab could be a safe option for patients with diffuse large B-cell lymphoma (DLCL) and mantle cell lymphoma (MCL).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Coiffier, B., Haioun, C., Ketterer, N., et al.[2022]

In a study of 83 patients with Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia, switching between the reference rituximab and its biosimilars (TRUXIMA and RIXATHON) did not lead to any new safety concerns, with adverse events being similar to those reported in existing literature.

Out of 465 rituximab infusions, 84.5% of patients experienced at least one adverse event, but only 5.9% had serious grade 3-4 events, indicating that the biosimilars are as safe as the reference product when switching is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of switching between rituximab biosimilars in onco-hematology. Urru, SAM., Spila Alegiani, S., Guella, A., et al.[2021]

Rituximab significantly reduces the annualized relapse rates in patients with relapsing-remitting multiple sclerosis, with a decrease of 0.80 relapses per year based on a meta-analysis of 15 studies involving 946 patients.

The treatment is well tolerated, with only mild-to-moderate adverse events occurring in 29.6% of patients and no severe adverse events reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab for relapsing-remitting multiple sclerosis: A systematic review and meta-analysis. Hu, Y., Nie, H., Yu, HH., et al.[2019]

A phase 3 trial involving 140 adults with advanced-stage follicular lymphoma showed that the rituximab biosimilar CT-P10 has comparable efficacy to rituximab, with similar progression-free survival rates (61% for CT-P10 vs. 55% for rituximab) after 4 years.

Both CT-P10 and rituximab had similar long-term safety profiles, with 90% of CT-P10 patients and 86% of rituximab patients experiencing treatment-emergent adverse events, indicating that CT-P10 is a safe alternative for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of CT-P10 or rituximab in untreated advanced follicular lymphoma: a randomized phase 3 study. Buske, C., Jurczak, W., Sancho, JM., et al.[2021]

In a study of 20 newly diagnosed patients with Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL), Zytux™ showed an overall response rate of 85%, with 35% achieving a complete response and 50% a partial response, indicating its efficacy in treating these conditions.

Zytux™ demonstrated a safety profile comparable to the reference drug MabThera®, suggesting it may be a viable alternative with similar or improved safety and efficacy for patients with NHL and CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of biosimilar rituximab (ZytuxTM) in newly diagnosed patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia. Alwan, AF., Abdulsahib, MA., Abbas, DD., et al.[2020]

In a study of 183 non-Hodgkin lymphoma patients treated with rituximab, the incidence of late-onset neutropenia (LON) was found to be 6%, with a median onset time of 75 days after treatment.

While most cases of LON were asymptomatic and resolved within 100 days, there were instances of serious complications, including infections, highlighting the need for careful monitoring of patients undergoing rituximab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late-Onset Neutropenia After Rituximab-Containing Therapy for Non-Hodgkin Lymphoma. Aguiar-Bujanda, D., Blanco-Sánchez, MJ., Hernández-Sosa, M., et al.[2015]

Rituximab was the first monoclonal antibody approved for cancer therapy and has significantly improved survival rates in patients with diffuse large cell lymphoma when combined with CHOP chemotherapy.

Initially approved in 1997 for relapsed or refractory low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma, rituximab is also being researched for other B-cell malignancies and nonmalignant diseases like autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. King, KM., Younes, A.[2015]

Rituximab is a highly effective monoclonal antibody for treating various B-cell lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, demonstrating a strong activity with low toxicity.

The combination of rituximab with chemotherapy (R-CHOP) has shown the highest efficacy reported for any chemotherapy regimen in treating diffuse large B-cell lymphoma and follicular lymphoma, although some patients may still be resistant to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab therapy in malignant lymphoma. Coiffier, B.[2022]

References

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

Rituximab for the treatment of non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. [2021]

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

Spotlight on rituximab in chronic lymphocytic leukemia, low-grade or follicular lymphoma, and diffuse large B-cell lymphoma. [2017]

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

Rituximab: a review of its use in chronic lymphocytic leukaemia, low-grade or follicular lymphoma and diffuse large B-cell lymphoma. [2021]

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

An Evidence-based Review of Anti-CD20 Antibody-containing Regimens for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Diffuse Large B-cell Lymphoma, or Follicular Lymphoma. [2019]

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

Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety of switching between rituximab biosimilars in onco-hematology. [2021]

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

Efficacy and safety of rituximab for relapsing-remitting multiple sclerosis: A systematic review and meta-analysis. [2019]

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

Long-term efficacy and safety of CT-P10 or rituximab in untreated advanced follicular lymphoma: a randomized phase 3 study. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of biosimilar rituximab (ZytuxTM) in newly diagnosed patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia. [2020]

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

Late-Onset Neutropenia After Rituximab-Containing Therapy for Non-Hodgkin Lymphoma. [2015]

11. England pubmed.ncbi.nlm.nih.gov

Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. [2015]

12. England pubmed.ncbi.nlm.nih.gov

Rituximab therapy in malignant lymphoma. [2022]