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

Sponsor

Enterome (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04669171

Collaborator

(none)

Enrollment

Locations

Arms

98.9

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma Marginal Zone Lymphoma	Biological: EO2463 Drug: lenalidomide Biological: rituximab	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 5, 2021

Anticipated Primary Completion Date :

Sep 30, 2024

Anticipated Study Completion Date :

Sep 30, 2029

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Phase 1: Recommended Phase 2 Dose | Adverse Events Assessment | [Up to 24 months]
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.
Phase 2: Overall Response Rate [Up to 24 months]
Overall Response Rate According to the Lugano Classification 2014 during EO2463 Monotherapy

Secondary Outcome Measures

Safety and Tolerability for EO2463 Administered as Monotherapy and in Combination with Lenalidomide, Rituximab and Lenalidomide/Rituximab [Up to 24 months]
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
Assessment of the Immunogenicity in Relation to OMP72, OMP64, OMP65, OMP66, and UCP2 that Compose EO2463 [Up to 24 months]
Immunogenicity will be assessed by interferon-Gamma (IFN-Γ) enzyme-Linked immunospot , and by intracellular cytokines staining, and multimers staining assays
Overall Response Rate [Up to 24 months]
Overall Response Rate as described by the Lugano Classification 2014, and by the Lymphoma Response to Immunomodulatory Therapy Criteria (Lyric) 2016 by trial cohort
Duration of response [Up to 7 years after last patient enrolled]
Duration of Response as described by the Lugano Classification 2014, and by the Lymphoma Response to Immunomodulatory Therapy Criteria (Lyric) 2016 by trial cohort
Evaluation of Overall Survival [Up to 7 years after last patient enrolled]
The time interval from the date of first study treatment administration to the date of death due to any cause

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 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.
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).
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.
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 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 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
2	Mayo Clinic	Rochester	Minnesota	United States	55905
3	University of Rochester Medical Center (URMC) - Wilmot Cancer Institute (WCI) (James P. Wilmot Cancer Center)	Rochester	New York	United States	14642
4	University of Washington-Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
5	University of Bologna	Bologna		Italy
6	IRCCS Policlinico San Matteo Foundation - University of Pavia	Naples		Italy
7	IRCCS Policlinico San Matteo Foundation - University of Pavia	Pavia		Italy
8	University Hospital Vall d'Hebron, Institute of Oncology	Barcelona		Spain
9	Clinica Universidad de Navarra	Madrid		Spain
10	Hospital Clinico Universitario de Salamanca	Salamanca		Spain