Clinical trial NCT04669171: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Follicular Lymphoma
Marginal Zone Lymphoma
Keywords: Follicular Lymphoma
Marginal Zone Lymphoma
Rituximab
Lenalidomide
Vaccine
Lead sponsor: Enterome
Sponsor class: INDUSTRY
First posted: 2020-12-16
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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

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

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.
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 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 allogeneic 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.

Primary outcomes:
measure: Phase 1: Recommended Phase 2 Dose | Adverse Events Assessment |
timeFrame: Up to 24 months
measure: Phase 2: Overall Response Rate
timeFrame: Up to 24 months
Secondary outcomes:
measure: Safety and Tolerability for EO2463 Administered as Monotherapy and in Combination with Lenalidomide, Rituximab and Lenalidomide/Rituximab
timeFrame: Up to 24 months
measure: Assessment of the Immunogenicity in Relation to OMP72, OMP64, OMP65, OMP66, and UCP2 that Compose EO2463
timeFrame: Up to 24 months
measure: Overall Response Rate
timeFrame: Up to 24 months
measure: Duration of response
timeFrame: Up to 7 years after last patient enrolled
measure: Evaluation of Overall Survival
timeFrame: Up to 7 years after last patient enrolled
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Rochester
country: United States
facility: University of Rochester Medical Center (URMC) - Wilmot Cancer Institute (WCI) (James P. Wilmot Cancer Center)
state: New York
city: Seattle
country: United States
facility: University of Washington-Seattle Cancer Care Alliance
state: Washington
city: Amiens
country: France
facility: CHU d'Amiens-Picardie - Hopital SUD
city: Bologna
country: Italy
facility: University of Bologna
city: Naples
country: Italy
facility: IRCCS Policlinico San Matteo Foundation - University of Pavia
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo Foundation - University of Pavia
city: Barcelona
country: Spain
facility: University Hospital Vall d'Hebron, Institute of Oncology
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
Study officials:
affiliation: Enterome
name: Jan Fagerberg, MD
role: STUDY_DIRECTOR
References: