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

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

Overview

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

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

Interventions

• Biological EO2463
  Multiple dose of EO2463
• Drug lenalidomide
  D1-21 of 4-weekly cycles
• Biological rituximab
  Multiple doses of rituximab

Primary outcome measures

• Phase 1: Recommended Phase 2 Dose | Adverse Events Assessment | [Time frame: Up to 24 months]
• Phase 2: Overall Response Rate [Time frame: Up to 24 months]
• Phase 2: Complete Response Rate [Time frame: Up to 24 months]

Secondary outcome measures (2)

• Assessment of the Immunogenicity in Relation to OMP72, OMP64, OMP65, OMP66, and UCP2 that Compose EO2463 [Time frame: Up to 24 months]
• Evaluation of Overall Survival [Time frame: Up to 7 years after last patient enrolled]

Eligibility criteria

Inclusion criteria

• 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.
• 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.
• 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.
• Patients with an age ≥ 18 years old.
• Patients who are human leukocyte antigen (HLA)-A2 positive.
• 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.
• Males or non-pregnant, non-lactating, females.
• Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
• Patients having received the information sheet and who have provided written informed consent prior to any study-related procedures.

Exclusion criteria

• 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.
• Patients with grade 3B FL or transformation to an aggressive lymphoma subtype.
• 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).
• Patients with prior exposure to EO2463.
• 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.
• 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.
• Patients to be included in Cohorts 4, who received prior CAR T-cell therapy and progressed within 6 months after this therapy.
• Patients with abnormal laboratory values.
• Patients with persistent Grade 3 or 4 toxicities.
• Uncontrolled central nervous system (CNS) metastasis.
• Other malignancy or prior malignancy with a disease-free interval of less than 3 years.
• Patients with clinically significant disease.
• Patients with suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g. Guillain-Barré syndrome).
• Patients with history of solid organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Pregnant and breastfeeding patients.
• Patients with history or presence of human immunodeficiency virus and/or potentially active hepatitis B virus/hepatitis C virus infection.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• Dana Farber Cancer Institute — Boston
• Mayo Clinic — Rochester
• University of Rochester Medical Center (URMC) - Wilmot Cancer Institute (WCI) (James P. Wi — Rochester
• University of Washington-Seattle Cancer Care Alliance — Seattle

Spain · 4 centers

• University Hospital Vall d'Hebron, Institute of Oncology — Barcelona
• Clinica Universidad de Navarra — Madrid
• Clinica Universidad de Navarra — Pamplona
• Hospital Clinico Universitario de Salamanca — Salamanca

Italy · 3 centers

• University of Bologna — Bologna
• IRCCS Policlinico San Matteo Foundation - University of Pavia — Naples
• IRCCS Policlinico San Matteo Foundation - University of Pavia — Pavia

France · 1 center

• CHU d'Amiens-Picardie - Hopital SUD — Amiens

Identifiers

NCT: NCT04669171 · EONHL1-20

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗