Epcoritamab + Rituximab for Follicular Lymphoma

Recruiting at 3 trial locations

Overseen By Heather A Walker, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Reid Merryman, MD

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Heart failure, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 9-10 months

35 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine how effective and safe the combination of rituximab and epcoritamab is in treating patients with Follicular Lymphoma (FL) and who have not received other treatments for their lymphoma. The names of the study drugs involved in this study are: * Rituximab (a type of monoclonal antibody therapy) * Epcoritamab (a T-cell bispecific antibody)

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressive therapy or taking more than 10 mg of prednisone daily, you may not be eligible to participate.

What data supports the effectiveness of the drug combination Epcoritamab and Rituximab for treating follicular lymphoma?

Rituximab, a key component of the treatment, has been shown to improve survival rates and increase the time patients live without their disease getting worse when combined with chemotherapy for follicular lymphoma. This suggests that combining Rituximab with other drugs, like Epcoritamab, could potentially enhance treatment effectiveness. ^{1 2 3 4 5}

Is the combination of Epcoritamab and Rituximab safe for treating follicular lymphoma?

Rituximab has been used for many years in treating follicular lymphoma and is generally considered safe, though it can cause mild side effects like fever and chills, especially during the first infusion. Serious side effects are rare, but new safety alerts can arise, so it's important for doctors to monitor patients closely. ^{6 7 8 9 10}

What makes the drug combination of Epcoritamab and Rituximab unique for treating follicular lymphoma?

The combination of Epcoritamab and Rituximab is unique because it pairs a novel bispecific antibody (Epcoritamab) that targets both CD3 and CD20 proteins on immune cells, with Rituximab, a well-established anti-CD20 antibody. This dual-targeting approach may enhance the immune system's ability to attack lymphoma cells more effectively than traditional treatments. ^{3 5 11 12 13}

Research Team

Reid W Merryman, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults with untreated Follicular Lymphoma (FL) who are not in urgent need of chemotherapy can join this trial. They must have good organ function, no prior systemic therapy for FL except radiation or short steroids, and agree to use effective contraception. Exclusions include recent major surgery, active infections like hepatitis B/C or HIV, severe medical conditions affecting study participation, certain heart issues within the last 6 months, pregnancy, breastfeeding intentions during the study period.

Inclusion Criteria

Examples of contraceptive methods with a failure rate of <1% per year.

I have not had any drug treatments for follicular lymphoma, but I may have had radiation or steroids.

Willingness to remain abstinent or to use two effective contraceptive methods.

Exclusion Criteria

I have severe heart failure or my heart pumps less blood than normal.

I have not had major surgery or significant injury in the last 4 weeks.

I do not have any severe or uncontrolled medical conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Rituximab and Epcoritamab. Cycle 1 includes Rituximab on Days -14, -7, 1, 8 and Epcoritamab on Days 1, 8, 15, 22 of a 6-week cycle. Cycles 2-3 include Epcoritamab on Days 1, 8, 15, 22 of a 4-week cycle. Cycles 4-9 include Epcoritamab on Days 1 and 15 of a 4-week cycle.

9-10 months

Multiple visits per cycle for drug administration and evaluations

Follow-up

Participants are monitored for safety and effectiveness after treatment, with surveillance imaging at months 13, 18, and 24, and follow-up visits for up to 5 years.

5 years

Long-term follow-up

Participants are monitored for long-term outcomes, including overall survival and incidence of histological transformation, for up to 10 years.

10 years

Treatment Details

Interventions

• Epcoritamab
• Rituximab

Trial Overview The trial is testing a combination of two drugs: Rituximab (a monoclonal antibody) and Epcoritamab (a T-cell bispecific antibody), to see how safe and effective they are together as a first-line treatment for patients with Follicular Lymphoma who haven't been treated before.

Participant Groups

Group I: Epcoritamab + Rituximab Experimental Treatment 2 Interventions

Participants will undergo study procedures as outlined: * PET/CT scans at baseline and after cycles 2, 5, and 9 of treatment. * Cycle 1: * Days -14, -7, 1, 8 of 6 week cycle: Predetermined dose of Rituximab. * Days 1, 8, 15, 22 of 6 week cycle: Predetermined dose of Epcoritamab. (Day 15 of Epcoritamab dosage will be administered in the hospital.) * Cycles 2 - 3: --Days 1, 8, 15, 22 of 4 week cycle: Predetermined dose of Epcoritamab. * Cycles 4 - 9: * Day 1 of 4 week cycle: Predetermined dose of Epcoritamab. * Day 15 of 4 week cycle: Predetermined dose of Epcoritamab. * Surveillance imaging (PT/CT scans) at months 13, 18, and 24 after initiation of treatment. * Follow up visits for up to 5 years.

Epcoritamab is already approved in United States, European Union for the following indications:

Approved in United States as Epkinly for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
• Diffuse large B-cell lymphoma after two or more lines of systemic therapy

Approved in European Union as Tepkinly for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
• Relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

Reid Merryman, MD

Lead Sponsor

Trials

3

Recruited

110+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Genmab

Industry Sponsor

Trials

76

Recruited

15,300+

Dr. Jan van de Winkel

Genmab

Chief Executive Officer since 2010

PhD in Immunology, University of Utrecht

Dr. Judith Klimovsky

Genmab

Chief Medical Officer since 2019

MD, University of Copenhagen

Findings from Research

Rituximab combined with chemotherapy significantly improves response rates and progression-free survival (PFS) in patients with advanced stage symptomatic follicular non-Hodgkin's lymphoma (NHL), without increasing toxicity, based on data from large-scale phase III trials.

Patients with follicular NHL should receive rituximab plus chemotherapy as first-line treatment, and maintenance therapy with rituximab has been shown to further prolong PFS in both relapsed and newly diagnosed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of rituximab in patients with follicular lymphoma. Marcus, R.[2019]

The use of the anti-CD20 monoclonal antibody rituximab has significantly improved survival rates in patients with follicular lymphoma (FL), especially when used in combination with chemotherapy for both induction and maintenance therapy.

Radioimmunotherapy (RIT) using radiolabelled anti-CD20 mAbs, such as (90)Y Ibritumomab tiuxetan and (131)I Tositumomab, has shown high response rates and durable remissions, particularly when used as consolidation therapy after initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How have outcomes for patients with follicular lymphoma changed with the addition of monoclonal antibodies? Illidge, T., Chan, C.[2019]

Rituximab is highly effective for treating low-grade CD20+ lymphoma, especially when combined with chemotherapy, which is the standard treatment for follicular lymphoma (FL).

The efficacy of rituximab can be enhanced by combining it with biological agents like interferon-alpha-2a, bortezomib, or lenalidomide, but more research is needed to determine the best combinations and timing of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. Kimby, E.[2021]

In a study of 60 patients with symptomatic or bulky follicular lymphoma, a combination of short-course chemoimmunotherapy (CHOP-R) followed by radioimmunotherapy (RIT) led to a significant increase in complete response (CR) rates, from 40% after CHOP-R to 82% after RIT, as assessed by imaging.

The study found that patients who did not achieve a complete metabolic response on PET imaging after CHOP-R had a higher risk of relapse, highlighting the importance of early PET assessment in predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Jacobs, SA., Swerdlow, SH., Kant, J., et al.[2016]

Rituximab, an anti-CD20 antibody, is a key treatment for follicular lymphoma, used both alone and in combination with chemotherapy for inducing remission and maintenance therapy.

Innovative therapies, such as ibritumomab tiuxetan, which combines anti-CD20 antibodies with radionuclides, show comparable effectiveness to rituximab, and ongoing trials are exploring more intensive treatment regimens that may improve outcomes or offer curative potential for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapy of follicular lymphoma]. Buske, C., Unterhalt, M., Hiddeman, W.[2018]

Rituximab is an effective treatment for follicular lymphoma (FL), improving outcomes when used in combination with traditional chemotherapy, and has shown significant benefits as a maintenance therapy without increasing side effects or compromising patients' quality of life.

Despite its long history of use, new safety alerts and side effects have emerged that clinicians need to be aware of, highlighting the importance of ongoing monitoring and management in patients receiving rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma. Aguiar-Bujanda, D., Blanco-Sánchez, MJ., Hernández-Sosa, M., et al.[2022]

Ofatumumab, a fully humanized anti-CD20 monoclonal antibody, demonstrated an overall response rate (ORR) of 84% in patients with untreated, low/intermediate-risk advanced-stage follicular lymphoma, indicating strong efficacy as a single-agent treatment.

The treatment was well tolerated, with no severe infusion reactions or serious infections reported, and a low discontinuation rate of 6%, suggesting that ofatumumab is a safe alternative to rituximab for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 multicentre study of single-agent ofatumumab in previously untreated follicular lymphoma: CALGB 50901 (Alliance). Rosenbaum, CA., Jung, SH., Pitcher, B., et al.[2021]

Obinutuzumab, when compared to rituximab, significantly improves progression-free survival (PFS) in patients with CD20 positive B-cell non-Hodgkin lymphomas, but it also increases the incidence of serious adverse events (AEs).

Ofatumumab is less effective than rituximab in terms of overall response rate (ORR), while 90Y-ibritumomab tiuxetan shows a higher ORR but does not improve other survival metrics compared to rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20+ B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis. Luo, C., Wu, G., Huang, X., et al.[2023]

In a phase 2 study involving 80 adults with untreated follicular lymphoma, the combination of ibrutinib and rituximab showed a high overall response rate of 85% in the first treatment arm and 75% in the second arm, indicating strong efficacy.

The treatment was generally well-tolerated, with common side effects including fatigue, diarrhea, and nausea, while serious adverse events were rare, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of ibrutinib and rituximab demonstrates activity in first-line follicular lymphoma. Fowler, NH., Nastoupil, L., De Vos, S., et al.[2021]

The combination of rituximab and fludarabine in treating chronic lymphocytic leukemia (CLL) showed an impressive overall response rate of 87%, with 85% of previously untreated patients responding positively.

The treatment was generally safe, with mild side effects reported in most patients, although there were instances of significant hematologic toxicity and one fatality due to cerebral bleeding, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia. Schulz, H., Klein, SK., Rehwald, U., et al.[2022]

Rituximab, when combined with chemotherapy (specifically cyclophosphamide, vincristine, and prednisone), has been approved as a front-line treatment for follicular lymphoma, showing significant benefits in progression-free survival and overall survival based on randomized Phase III studies.

The review highlights that the addition of rituximab to chemotherapy regimens not only improves patient outcomes but also represents a significant advancement in the management of follicular lymphoma over the past three decades.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on front-line therapy for follicular lymphoma: chemo-immunotherapy with rituximab and survival. Turturro, F.[2015]

The combination of epratuzumab and rituximab was well-tolerated in 59 untreated patients with follicular lymphoma, showing a high response rate of 88.2%, with 42.4% achieving complete responses.

At a 3-year follow-up, 60% of patients remained in remission, indicating that this non-chemotherapy approach can provide effective long-term outcomes similar to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 trial of extended induction epratuzumab and rituximab for previously untreated follicular lymphoma: CALGB 50701. Grant, BW., Jung, SH., Johnson, JL., et al.[2021]

Rituximab, a monoclonal antibody targeting CD20, has improved progression-free survival (PFS) and may enhance overall survival (OS) in patients with follicular non-Hodgkin's lymphoma when used in combination with chemotherapy.

The low toxicity of rituximab allows for maintenance therapy, which shows promise for providing a survival benefit, although the best administration schedule and cost-effectiveness are still under investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of follicular lymphoma--a review. Van Hende, V., Offner, F.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Use of rituximab in patients with follicular lymphoma. [2019]

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

How have outcomes for patients with follicular lymphoma changed with the addition of monoclonal antibodies? [2019]

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

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. [2021]

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

Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. [2016]

5. Germany pubmed.ncbi.nlm.nih.gov

[Therapy of follicular lymphoma]. [2018]

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

Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Phase 2 multicentre study of single-agent ofatumumab in previously untreated follicular lymphoma: CALGB 50901 (Alliance). [2021]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20+ B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis. [2023]

9. England pubmed.ncbi.nlm.nih.gov

The combination of ibrutinib and rituximab demonstrates activity in first-line follicular lymphoma. [2021]

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

Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia. [2022]

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

Update on front-line therapy for follicular lymphoma: chemo-immunotherapy with rituximab and survival. [2015]

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

A phase 2 trial of extended induction epratuzumab and rituximab for previously untreated follicular lymphoma: CALGB 50701. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Treatment of follicular lymphoma--a review. [2016]