EO2463 Combination Therapy for Non-Hodgkin's Lymphoma

(SIDNEY Trial)

Recruiting at 11 trial locations

Overseen By Karlijn Kroon, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Enterome

Must not be taking: Immunotherapy, Radionuclide therapy

Disqualifiers: Autoimmune disorder, CNS metastasis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests EO2463, a new treatment for Non-Hodgkin's Lymphoma (NHL), specifically targeting Follicular Lymphoma (FL) and Marginal Zone Lymphoma (MZL). The goal is to determine the safest and most effective dose and assess its efficacy alone and in combination with other treatments like lenalidomide (a cancer drug) and rituximab (an antibody therapy). Individuals with newly diagnosed or previously treated FL or MZL who can manage daily activities without major limitations might be suitable candidates. Participants must have a measurable tumor size and be willing to adhere to the study plan. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken certain treatments like dexamethasone above a specific dose or immunotherapy within a certain time before starting the trial. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that EO2463, a new treatment that aids the immune system in fighting disease, is generally easy for patients to handle. In earlier studies, using EO2463 alone yielded good results with manageable side effects. Some patients experienced mild reactions, but serious issues were rare. The treatment also received a special approval process from the FDA, indicating confidence in its safety.

When combined with rituximab, EO2463 maintained a good safety record. Studies found this combination manageable, with no new safety concerns.

EO2463 was also tested with both lenalidomide and rituximab. This combination was well-tolerated, with safety results similar to using each treatment individually. The safety data from these studies suggest that EO2463, whether used alone or with other treatments, is safe for further testing in people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Non-Hodgkin's Lymphoma, which often involve chemotherapy and immunotherapy like rituximab, EO2463 offers a novel approach. This treatment is unique because it uses a combination therapy strategy that targets cancer cells with precision, potentially enhancing the effectiveness of the immune response. Researchers are particularly excited about EO2463's ability to be combined with existing drugs like lenalidomide and rituximab, which could improve outcomes for both untreated and previously treated patients. This innovative approach aims to provide more tailored and effective treatment options, reducing the need for more aggressive therapies and improving patient quality of life.

What evidence suggests that this trial's treatments could be effective for Non-Hodgkin's Lymphoma?

Research has shown that EO2463 holds promise for treating a slow-growing type of non-Hodgkin's lymphoma (NHL). In earlier studies, EO2463 alone led to a complete response in 78% of patients. In this trial, some participants will receive EO2463 monotherapy, while others will receive EO2463 combined with other drugs. Specifically, one cohort will receive EO2463 with rituximab, and another will receive EO2463 with lenalidomide and rituximab. These findings suggest that EO2463, whether used alone or with other drugs, could effectively treat NHL by helping the immune system recognize and attack cancer cells. The treatment has also been well-tolerated, with no serious side effects reported. ^{1 5 6 7 8}

Who Is on the Research Team?

Jan Fagerberg, MD

Principal Investigator

Enterome

Are You a Good Fit for This Trial?

Adults over 18 with certain types of indolent Non-Hodgkin Lymphoma (NHL) such as Follicular Lymphoma or Marginal Zone Lymphoma. Participants must have measurable disease, be HLA-A2 positive, and can include both newly diagnosed and those who've relapsed after treatment. Excludes pregnant women, individuals on high-dose steroids, those with aggressive lymphoma subtypes or other recent cancers, uncontrolled brain metastasis, autoimmune disorders, organ transplants, HIV/HBV/HCV infections.

Inclusion Criteria

Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.

I am HLA-A2 positive.

I am a male or a female not pregnant or breastfeeding.

Exclusion Criteria

I have previously been treated with EO2463.

I have or might have an autoimmune disorder, including conditions like Guillain-Barré syndrome.

I do not have uncontrolled brain metastasis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

EO2463 monotherapy for 6 weeks, followed by combination with lenalidomide and/or rituximab

24 months

Weekly visits during initial treatment phase

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 7 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• EO2463
• Lenalidomide
• Rituximab

Trial Overview The trial is testing EO2463 alone and in combination with lenalidomide and/or rituximab to determine the optimal dose for Phase 2 trials. It aims to assess safety, tolerability, immune response generation (immunogenicity), and initial effectiveness against indolent NHL.

How Is the Trial Designed?

Group I: Cohort 4 Experimental Treatment 3 Interventions

15 Previously treated patients with FL Or MZL. Evaluation of EO2463 at the established dose in Cohort 1 in combination with lenalidomide and with addition of rituximab from week 19 onwards (depending on response)

Group II: Cohort 3 Experimental Treatment 2 Interventions

15 Previously untreated patients with FL or MZL. Evaluation of EO2463 at the established dose in cohort 1 as monotherapy for 6 weeks and in combination with rituximab from week 7

Group III: Cohort 2 Experimental Treatment 1 Intervention

15 Previously untreated patients with FL Or MZL. Evaluation of EO2463 monotherapy at the established dose in Cohort 1

Group IV: Cohort 1 Experimental Treatment 3 Interventions

Safety Lead-In, Dose-Finding, Cohort, with a 3-by-3 design of EO2463 for 6 weeks followed by addition of lenalidomide week 7 and rituximab week 19 (depending on response). Four to 18 evaluable (previously treated) patients with Follicular Lymphoma (FL) or Marginal Zone Lymphoma (MZL) will be Included based on safety findings

Who Is Running the Clinical Trial?

Enterome

Lead Sponsor

Trials

9

Recruited

550+

Published Research Related to This Trial

Rituximab, an anti-CD20 monoclonal antibody, is now a standard treatment for non-Hodgkin's lymphoma, effective both as a standalone therapy for indolent lymphoma and in combination with chemotherapy for aggressive lymphoma.

New monoclonal antibodies targeting various molecules on lymphoma cells are in clinical development, showing potential for enhanced efficacy, especially when combined with existing therapies or when radioconjugated with anti-CD20 antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody therapy for non-Hodgkin's lymphoma. Ansell, SM.[2015]

Oral etoposide is an effective treatment for patients with previously treated lymphomas, showing clear benefits and good tolerability, especially in elderly or medically unfit patients.

The optimal dosing schedule for oral etoposide appears to be low daily doses of 50 to 100 mg for 10 to 14 days, but further studies are needed to determine its effectiveness in combination with other chemotherapy agents in previously untreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral etoposide in lymphoma. Greco, FA.[2018]

In a study involving 20 patients with untreated advanced non-Hodgkin's lymphoma, the MECHOP-BM regimen resulted in a 78% overall response rate, with 33% achieving a complete response (CR).

The most significant side effect observed was leukopenia, with a mean white blood cell count dropping to 1,300/microliters, indicating that while MECHOP-BM is effective, it can lead to serious reductions in immune function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[MECHOP-BM chemotherapy in the treatment of non Hodgkin's lymphoma]. Inoue, N., Miyazaki, E., Okada, M., et al.[2006]

In a study of 18 patients with advanced aggressive non-Hodgkin's lymphoma, a combination treatment of mitoxantrone, etoposide, cisplatin, and prednisolone resulted in a 61% overall response rate, with four complete and seven partial responses.

The treatment was generally well-tolerated despite myelosuppression being the main side effect, and responders had a median survival time of 52 weeks compared to 24 weeks for nonresponders, suggesting the regimen's potential effectiveness in relapsed or resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage chemotherapy for non-Hodgkin's lymphoma with a combination of mitoxantrone, etoposide, cisplatin, and prednisolone. Ohnoshi, T., Hayashi, K., Ueoka, H., et al.[2013]

In a study of 115 patients with Waldeyer's ring diffuse large B-cell lymphoma, those treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) showed significantly better progression-free survival (PFS) and overall survival (OS) compared to those receiving standard R-CHOP treatment, with 2-year PFS rates of 90.1% versus 80.5%.

The DA-EPOCH-R treatment was associated with fewer deaths (2 out of 42 patients) compared to R-CHOP (9 out of 42 patients) during a median follow-up of 45 months, while both treatments had similar clinical responses and treatment-related toxicities, indicating that DA-EPOCH-R is a safer and more effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution. Liang, Y., Liu, X., Yang, J., et al.[2023]

The ESHAP chemotherapy regimen showed a 53.1% overall response rate in 32 Chinese patients with refractory non-Hodgkin's lymphoma, with 31.3% achieving complete remission lasting an average of 12.2 months.

While ESHAP was effective, it had significant side effects, including severe myelosuppression and infections, and most patients relapsed within 2 years, indicating limited long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ESHAP as salvage therapy for refractory non-Hodgkin's lymphoma: Taiwan experience. Wang, WS., Chiou, TJ., Liu, JH., et al.[2019]

Intensifying drug regimens for intermediate- and high-grade non-Hodgkin's lymphomas has successfully improved cure rates, especially with the use of growth factors and stem cell transfusions to manage side effects.

In low-grade lymphomas, while intensive therapy is more controversial, promising results show that durable remissions can be achieved in advanced-stage patients through low-dose radiation or autologous transplantation, particularly in those with good prognostic factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of non-Hodgkin's lymphoma. Portlock, CS.[2019]

Recent phase III trials indicate that using second- and third-generation treatment regimens does not improve outcomes for patients with aggressive lymphomas, highlighting the need for new strategies.

Preliminary results suggest that while standard therapies with growth factor support show minimal benefits, high-risk patients achieving complete remission may benefit from consolidative bone marrow transplantation, and novel high-dose regimens could offer promising alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of aggressive histology lymphoma. Bartlett, NL.[2019]

The combination of vorinostat and rituximab showed a 46% overall response rate in 28 patients with indolent B-cell non-Hodgkin lymphoma, with a higher response of 67% in previously untreated patients, indicating its efficacy as a treatment option.

The regimen was well tolerated over a median follow-up of 25.6 months, with the most common serious side effects being manageable, suggesting a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of vorinostat and rituximab for treatment of newly diagnosed and relapsed/refractory indolent non-Hodgkin lymphoma. Chen, R., Frankel, P., Popplewell, L., et al.[2018]

The MEB chemotherapy regimen (mitoxantrone, etoposide, and bleomycin) showed promising antitumor activity in patients with non-Hodgkin's lymphoma, achieving major responses in 50% of the 22 treated patients, including 23% complete responses.

Despite a significant incidence of grade 3-4 neutropenia in 59% of patients, the toxicity profile was considered manageable, indicating that MEB could be a viable treatment option for patients who are not eligible for standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitoxantrone, Etoposide and bleomycin (meb) chemotherapy in non-hodgkins-lymphoma patients non-elegible for standard cyclophosphamide, Doxorubicin, vincristine and prednisone (chop) combination. Tagliaferri, P., Matano, E., Rea, A., et al.[2019]

In a study of 28 patients with recurrent or refractory lymphoma treated with the E-SHAP regimen, no objective responses were observed, indicating limited efficacy of this treatment in this patient population.

The treatment was associated with significant toxicity, particularly myelosuppression, leading to over half of the patients requiring hospitalization for neutropenia-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

E-SHAP: inadequate treatment for poor-prognosis recurrent lymphoma. Johnson, PW., Sweetenham, JW., McCallum, P., et al.[2020]

The chimeric anti-CD20 monoclonal antibody IBI301 was well tolerated in nine Chinese patients with CD20(+) B-cell non-Hodgkin's lymphoma, with no severe adverse events or dose-limiting toxicities reported during the study.

IBI301 effectively eliminated peripheral CD20-expressing B cells in all patients, indicating its potential efficacy in targeting B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tolerance and pharmacodynamics phase Ⅰ clinical trial study of chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients with CD20-positive non-Hodgkin's lymphoma]. Jiang, B., Qi, JY., Sun, MY., et al.[2020]

The introduction of new combination chemotherapy regimens in the 1970s significantly improved treatment outcomes for patients with aggressive non-Hodgkin's lymphoma (NHL).

Recent controlled studies have shown that newer, more intensive treatment regimens have not consistently led to better results, raising questions about the effectiveness of these advancements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of aggressive non-Hodgkin's lymphoma in adults--are we doing any better? Hagberg, H., Kimby, E.[2020]

Citations

1. enterome.com enterome.com/wp-content/uploads/2024/12/2024-ENT-12-SIDNEY-ASH-Presented-Data-final-1-2.pdf

Enterome's Immunotherapy EO2463 Shows Early Clinical ... 46% objective response rate, with 15% complete responses and 31% partial responses in patients with early-stage follicular lymphoma reported ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.7058

Phase 1/2 of EO2463 immunotherapy as monotherapy and ... No related grade ≥3 adverse events were seen with EO2463 monotherapy. Most common related events were grade 1 to 2 local administration site ...

3. targetedonc.com targetedonc.com/view/immunotherapy-eo2463-receives-fda-fast-track-for-follicular-lymphoma

Immunotherapy EO2463 Receives FDA Fast Track for ... FDA fast-tracks EO2463 immunotherapy for follicular lymphoma, promising a new treatment option backed by positive trial data and innovative ...

4. firstwordpharma.com firstwordpharma.com/story/5975228

Enterome reports positive Phase 2 results for EO2463 in ... 60% (12/20) complete response rate after treatment with EO2463 in combination with lenalidomide and rituximab (R2). EO2463 plus R2 was well ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20521962

A Novel Vaccine (EO2463) as Monotherapy and in ... The purpose of this study is to define the recommended dose, safety, tolerability, immunogenicity, and preliminary effectiveness of EO2463 ...

6. enterome.com enterome.com/news-events/enterome-to-present-clinical-data-on-eo2463-in-b-cell-lymphoma-at-the-2024-american-society-of-clinical-oncology-asco-annual-meeting/

Enterome to Present Clinical Data on EO2463 in B-cell ... The study aims to assess the safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 monotherapy and combination therapy in ...

7. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_14350.a-novel-vaccine-eo2463-as-monotherapy-and-in-combination-for-treatment-of-patients-with-indolent-non-hodgkin-lymphoma-sidney.html

A Novel Vaccine (EO2463) as Monotherapy and in ... A Novel Vaccine (EO2463) as Monotherapy and in Combination, for Treatment of Patients With Indolent Non-Hodgkin Lymphoma (SIDNEY). Complete ...

8. onclive.com onclive.com/view/fda-grants-fast-track-designation-to-eo2463-for-follicular-lymphoma

FDA Grants Fast Track Designation to EO2463 for ... The FDA granted fast track to EO2463, an OncoMimics immunotherapy, for low–tumor burden follicular lymphoma in the watch-and-wait setting.