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

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

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

Study Overview

• Status: Recruiting
• Conditions: Follicular Lymphoma; Marginal Zone Lymphoma
• Intervention / Treatment: Biological: EO2463; Drug: lenalidomide; Biological: rituximab

Detailed 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

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Karlijn Kroon, MD; Phone Number: +33 611300589; Email: kkroon-ext@enterome.com
• Study Contact Backup: Name: Jan Fagerberg, MD, PhD; Phone Number: +32 3 205 55 55; Email: medicalmonitoring-hem@enterome.com

Study Locations

• Italy
  • Bologna, Italy
    • Active, not recruiting
    • University of Bologna
  • Naples, Italy
    • Recruiting
    • IRCCS Policlinico San Matteo Foundation - University of Pavia
    • Contact: Antonio Pinto, Dr
  • Pavia, Italy
    • Recruiting
    • IRCCS Policlinico San Matteo Foundation - University of Pavia
    • Contact: Luca Arcaini, Dr
• Spain
  • Barcelona, Spain
    • Recruiting
    • University Hospital Vall d'Hebron, Institute of Oncology
    • Contact: Francisco Bosch Albareda, Dr
  • Madrid, Spain
    • Recruiting
    • Clinica Universidad de Navarra
    • Contact: Carlos Grande, Dr
  • Salamanca, Spain
    • Recruiting
    • Hospital Clinico Universitario de Salamanca
    • Contact: Ramon Garcia Sanz, Dr
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Not yet recruiting
      • Dana Farber Cancer Institute
      • Contact: Reid Merryman, Dr
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Jose Caetano Villasboas Bisneto, Dr
  • New York
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester Medical Center (URMC) - Wilmot Cancer Institute (WCI) (James P. Wilmot Cancer Center)
      • Contact: Jonathan Friedberg, Dr
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • University of Washington-Seattle Cancer Care Alliance
      • Contact: Stephen Smith, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 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	Biological: EO2463; Multiple dose of EO2463; Drug: lenalidomide; D1-21 of 4-weekly cycles; Other Names: Revlimid; Biological: rituximab; Multiple doses of rituximab; Other Names: MabThera
Experimental: Cohort 2; 15 Previously untreated patients with FL Or MZL. Evaluation of EO2463 monotherapy at the established dose in Cohort 1	Biological: EO2463; Multiple dose of EO2463
Experimental: Cohort 3; 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	Biological: EO2463; Multiple dose of EO2463; Biological: rituximab; Multiple doses of rituximab; Other Names: MabThera
Experimental: Cohort 4; 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)	Biological: EO2463; Multiple dose of EO2463; Drug: lenalidomide; D1-21 of 4-weekly cycles; Other Names: Revlimid; Biological: rituximab; Multiple doses of rituximab; Other Names: MabThera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Phase 2: Overall Response Rate	Overall Response Rate According to the Lugano Classification 2014 during EO2463 Monotherapy	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Assessment of the Immunogenicity in Relation to OMP72, OMP64, OMP65, OMP66, and UCP2 that Compose EO2463	Immunogenicity will be assessed by interferon-Gamma (IFN-Γ) enzyme-Linked immunospot , and by intracellular cytokines staining, and multimers staining assays	Up to 24 months
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
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
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

Collaborators and Investigators

• Sponsor: Enterome
• Investigators: Study Director: Jan Fagerberg, MD, Enterome

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2021
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): September 30, 2029

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: December 14, 2020
• First Posted (Actual): December 16, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Vaccine; Rituximab; Follicular Lymphoma; Marginal Zone Lymphoma; Lenalidomide
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, B-Cell; Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell, Marginal Zone; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Rituximab
• Other Study ID Numbers: EONHL1-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No