A Novel Vaccine (EO2463) as Monotherapy and in Combination, for Treatment of Patients With Indolent Non-Hodgkin Lymphoma
- Conditions
- Follicular LymphomaMarginal Zone Lymphoma
- Interventions
- Registration Number
- NCT04669171
- Lead Sponsor
- Enterome
- 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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
- 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, 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.
- 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 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 4 EO2463 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) Cohort 1 EO2463 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 Cohort 3 EO2463 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 Cohort 2 EO2463 15 Previously untreated patients with FL Or MZL. Evaluation of EO2463 monotherapy at the established dose in Cohort 1 Cohort 3 rituximab 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 Cohort 4 rituximab 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) Cohort 1 lenalidomide 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 Cohort 4 lenalidomide 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) Cohort 1 rituximab 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
- Primary Outcome Measures
Name Time Method Phase 2: Overall Response Rate Up to 24 months Overall Response Rate According to the Lugano Classification 2014 during EO2463 Monotherapy
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.
- Secondary Outcome Measures
Name Time Method 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
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
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
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
Trial Locations
- Locations (10)
CHU d'Amiens-Picardie - Hopital SUD
🇫🇷Amiens, France
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, United States
University of Bologna
🇮🇹Bologna, Italy
IRCCS Policlinico San Matteo Foundation - University of Pavia
🇮🇹Pavia, Italy
University Hospital Vall d'Hebron, Institute of Oncology
🇪🇸Barcelona, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
Hospital Clinico Universitario de Salamanca
🇪🇸Salamanca, Spain