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

Follicular Lymphoma Clinical Trial

— SIDNEY  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04669171
• Other study ID #: EONHL1-20
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 5, 2021
• Est. completion date: September 30, 2029

Study information

• Verified date: March 2024
• Source: Enterome
• Contact: Jan Fagerberg, MD, PhD
• Phone: +32 3 205 55 55
• Email: medicalmonitoring-hem[@]enterome.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to define the recommended Phase 2 Dose, safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 during monotherapy and in combination with lenalidomide and/or rituximab in patients with indolent NHL

Description:

EO2463 Is an innovative cancer peptide therapeutic vaccine based on the homologies between tumor associated antigens and microbiome-derived peptides that will be administered alone and in combination with lenalidomide, rituximab, and lenalidomide/rituximab to generate safety and preliminary efficacy data in patients with indolent NHL

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 30, 2029
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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, and not be in need of standard of care therapy according to the assessment of the treating physician.

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. 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 Groupe d'Etude des Lymphomes Folliculaires criteria and be in need of therapy according to the assessment of the treating physician.

5. Patients with an age = 18 years old.

6. Patients who are human leukocyte antigen (HLA)-A2 positive.

7. 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.

8. Males or non-pregnant, non-lactating, females.

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

10. 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 with abnormal laboratory values.

8. Patients with persistent Grade 3 or 4 toxicities.

9. Uncontrolled central nervous system (CNS) metastasis.

10. Other malignancy or prior malignancy with a disease-free interval of less than 3 years.

11. Patients with clinically significant disease.

12. Patients with suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g. Guillain-Barré syndrome).

13. Patients with history of solid organ transplantation or hematopoietic stem cell transplantation.

14. Pregnant and breastfeeding patients.

15. Patients with history or presence of human immunodeficiency virus and/or potentially active hepatitis B virus/hepatitis C virus infection.

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Non-Hodgkin
• Marginal Zone Lymphoma

Intervention

Biological:
• EO2463
Multiple dose of EO2463

Drug:
• lenalidomide
D1-21 of 4-weekly cycles

Biological:
• rituximab
Multiple doses of rituximab

Locations

Country	Name	City	State
Italy	University of Bologna	Bologna
Italy	IRCCS Policlinico San Matteo Foundation - University of Pavia	Naples
Italy	IRCCS Policlinico San Matteo Foundation - University of Pavia	Pavia
Spain	University Hospital Vall d'Hebron, Institute of Oncology	Barcelona
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Medical Center (URMC) - Wilmot Cancer Institute (WCI) (James P. Wilmot Cancer Center)	Rochester	New York
United States	University of Washington-Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Enterome

Countries where clinical trial is conducted

United States,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Recommended Phase 2 Dose | Adverse Events Assessment |	Incidences of adverse events, Treatment-Emergent Adverse events, Serious Adverse Events, Deaths, and Laboratory Abnormalities Using the National Cancer Institute-Common Terminology Criteria for Adverse events (NCI-CTCAE) V5.0.	Up to 24 months
Primary	Phase 2: Overall Response Rate	Overall Response Rate According to the Lugano Classification 2014 during EO2463 Monotherapy	Up to 24 months
Secondary	Safety and Tolerability for EO2463 Administered as Monotherapy and in Combination with Lenalidomide, Rituximab and Lenalidomide/Rituximab	Incidences Of Adverse Events, Treatment-Emergent Adverse events, Serious Adverse events, Deaths, Treatment Discontinuations/Delays, And Laboratory Abnormalities Using The NCI-CTCAE V5.0 Grading System	Up to 24 months
Secondary	Assessment of the Immunogenicity in Relation to OMP72, OMP64, OMP65, OMP66, and UCP2 that Compose EO2463	Immunogenicity will be assessed by interferon-Gamma (IFN-G) enzyme-Linked immunospot , and by intracellular cytokines staining, and multimers staining assays	Up to 24 months
Secondary	Overall Response Rate	Overall Response Rate as described by the Lugano Classification 2014, and by the Lymphoma Response to Immunomodulatory Therapy Criteria (Lyric) 2016 by trial cohort	Up to 24 months
Secondary	Duration of response	Duration of Response as described by the Lugano Classification 2014, and by the Lymphoma Response to Immunomodulatory Therapy Criteria (Lyric) 2016 by trial cohort	Up to 7 years after last patient enrolled
Secondary	Evaluation of Overall Survival	The time interval from the date of first study treatment administration to the date of death due to any cause	Up to 7 years after last patient enrolled