A new vaccine for treating indolent non-Hodgkin lymphoma

A Global Multicenter Phase 1/2 Trial of EO2463, a Novel Microbial-Derived Peptide Therapeutic Vaccine, as Monotherapy, and in Combination With Lenalidomide and Rituximab, for Treatment of Patients With Indolent Non-Hodgkin's Lymphoma

This study is testing a new vaccine for people with indolent non-Hodgkin lymphoma to see if it works well and is safe, both on its own and with other treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Enterome (Industry-sponsored)
• Drugs / interventions: rituximab, CAR T, immunotherapy, prednisone
• Locations: 12 sites (Boston, Massachusetts and 11 other locations)
• Trial ID: NCT04669171 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, tolerability, immunogenicity, and preliminary efficacy of a novel cancer peptide therapeutic vaccine, EO2463, administered alone and in combination with lenalidomide and/or rituximab in patients with indolent non-Hodgkin lymphoma (NHL). The trial includes multiple cohorts, targeting both relapsed/refractory and newly diagnosed patients with specific grades of follicular lymphoma and marginal zone lymphoma. Participants will receive the vaccine to determine the recommended Phase 2 dose and gather data on its effectiveness and safety profile.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with relapsed/refractory or newly diagnosed, biopsy-proven grade 1, 2, or 3A follicular lymphoma or marginal zone lymphoma.

Not a fit: Patients with aggressive forms of lymphoma or those who have not received prior treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this vaccine could provide a new treatment option for patients with indolent non-Hodgkin lymphoma, potentially improving outcomes and quality of life.

How similar studies have performed: While the approach of using a peptide therapeutic vaccine is innovative, similar studies have shown promise in the treatment of other cancers, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. For inclusion in Cohorts 1 and 4 patients should have relapsed/refractory, biopsy-proven grade 1, 2 or 3A, FL or MZL, ECOG performance status 0 to 2, and have received at least one prior line of treatment. For inclusion in Cohort 4b the above applies except that patients with FL, and not patients with MZL, will be eligible for enrollment.
2. For inclusion in Cohort 2 patients should have newly diagnosed, previously untreated (radiotherapy as only prior treatment is allowed), biopsy-proven grade 1, 2 or 3A, FL or MZL. ECOG performance status 0 or 1, low tumor burden by Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria, and not be in need of standard of care therapy according to the assessment of the treating physician.
3. For inclusion in Cohort 3 patients should have newly diagnosed, previously untreated (radiotherapy as only prior treatment is allowed), biopsy-proven grade 1, 2 or 3A, FL or MZL. ECOG performance status 0 or 1, low tumor burden by GELF criteria and be in need of therapy according to the assessment of the treating physician.
4. Patients with an age ≥ 18 years old.
5. Patients who are human leukocyte antigen (HLA)-A2 positive.
6. Patients should have radiologically measurable disease with a lymph node or tumor mass greater than or equal to 1.5 cm in at least one dimension.
7. Males or non-pregnant, non-lactating, females.
8. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
9. Patients having received the information sheet and who have provided written informed consent prior to any study-related procedures.

Exclusion Criteria:

1. Patients treated with dexamethasone \> 2 mg/day or equivalent (i.e. 13 mg/day of prednisone, or 53 mg/day of hydrocortisone) within 14 days before the first EO2463 administration, unless required to treat an adverse event.
2. Patients with grade 3B FL or transformation to an aggressive lymphoma subtype.
3. Patients with only one prior treatment and a high-risk profile as defined by first progression of disease within 24 months of diagnosis (the exclusion is not applicable for patients with more than one prior line treatment).
4. Patients with prior exposure to EO2463.
5. Patients treated with immunotherapy (meaning immunostimulatory or immunosuppressive therapy; beside excluded, or allowed, compounds per other inclusion/exclusion criteria specifications), radionuclide therapy, radiotherapy, cytoreductive therapy, or received treatment with any other investigational agent within 28 days before the first EO2463 administration.
6. Patients to be included in Cohorts 1 and 4, and who have received rituximab or other B cell ablation therapy within 8 weeks of start of study treatment.
7. Patients to be included in Cohorts 4, who received prior CAR T-cell therapy and progressed within 6 months after this therapy.
8. Patients with abnormal laboratory values.
9. Patients with persistent Grade 3 or 4 toxicities.
10. Uncontrolled central nervous system (CNS) metastasis.
11. Other malignancy or prior malignancy with a disease-free interval of less than 3 years.
12. Patients with clinically significant disease.
13. Patients with suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g. Guillain-Barré syndrome).
14. Patients with history of solid organ transplantation or allogeneic hematopoietic stem cell transplantation.
15. Pregnant and breastfeeding patients.
16. Patients with history or presence of human immunodeficiency virus and/or potentially active hepatitis B virus/hepatitis C virus infection.

Where this trial is running

Boston, Massachusetts and 11 other locations

• Dana Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
• Mayo Clinic — Rochester, Minnesota, United States (Recruiting)
• University of Rochester Medical Center (URMC) - Wilmot Cancer Institute (WCI) (James P. Wilmot Cancer Center) — Rochester, New York, United States (Recruiting)
• University of Washington-Seattle Cancer Care Alliance — Seattle, Washington, United States (Recruiting)
• CHU d'Amiens-Picardie - Hopital SUD — Amiens, France (Recruiting)
• University of Bologna — Bologna, Italy (Withdrawn)
• IRCCS Policlinico San Matteo Foundation - University of Pavia — Naples, Italy (Recruiting)
• IRCCS Policlinico San Matteo Foundation - University of Pavia — Pavia, Italy (Recruiting)
• University Hospital Vall d'Hebron, Institute of Oncology — Barcelona, Spain (Recruiting)
• Clinica Universidad de Navarra — Madrid, Spain (Recruiting)
• Clinica Universidad de Navarra — Pamplona, Spain (Recruiting)
• Hospital Clinico Universitario de Salamanca — Salamanca, Spain (Recruiting)

Study contacts

• Study coordinator: Jan Fagerberg, MD, PhD

Conditions Follicular Lymphoma; Marginal Zone Lymphoma; Rituximab; Lenalidomide; Peptide-based immunotherapy