Indolent Non-Hodgkin's Lymphoma (Follicular Lymphoma
Conditions
Interventions
Product Name: EO2463
Pharmaceutical Form: Emulsion for injection
INN or Proposed INN: N/A
Current Sponsor code: OMP72
Other descriptive name: OMP72
Concentration unit: µg microgram(s)
Concentration ty
Sponsors
Enterome
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 (no limitation in number of prior treatments; radiotherapy by itself is not considered a line of treatment). 2. 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, Ann Arbor stage III or IV, or Ann Arbor stage I or II when the patient is not eligible for definitive radiotherapy, 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. 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, Ann Arbor stage III or IV, ECOG performance status 0 or 1, low tumor burden by GELF criteria (low tumor burden defined as: no mass > 7 cm, 3 cm, no systemic or B-symptoms, no splenomegaly > 16 cm by PET/CT or CT scan, no risk of vital organ compression, no leukemic phase > 5,000/µL circulating lymphocytes, and no cytopenia [defined as platelets 40 mIU/mL), b. female and male, surgically sterile (e.g. bilaterally blocked or removed fallopian tubes, vas deferens), c. female of childbearing potential with a negative highly sensitive serum pregnancy test within 72 hours prior to first administration of study treatment and use of a highly effective contraception from signing the Informed Consent Form (ICF) through 30 days safety visit after the last study treatment dose administered; note, the male partner should in addition to the use of highly effective contraception by the female patient also use condoms, d. male patient with female partners of childbearing potential must use condoms from signing the ICF through 30 days safety visit after the last study treatment dose administered; in addition, male patients must ensure that their partners of childbearing potential also use highly effective contraception. In addition, for patients who are to be enrolled in a cohort including rituximab the following inclusion criteria are applicable: e. due to the long retention time of rituximab in patients with B cell depletion, females of childbearing potential must commit to use effective contraceptive methods (see protocol inclusion criteria 7d for details) during and for 12 months following treatment with rituximab. In addition, for patients who are to be enrolled in a cohort including lenalidomide the following inclusion criteria are applicable: f. females of reproductive potential: i. must avoid pregnancy for at least 4 weeks before beginning lenalidomide therapy, during therapy, during dose interruptions and for at least
Exclusion criteria
Exclusion criteria: 1. Patients treated with dexamethasone > 2 mg/day or equivalent (ie 13 mg/day of prednisone or 53 mg/day of hydrocortisone) within 14 days before the first EO2463 administration. 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 according to the following list (note, lab ranges according to the performing laboratory's reference ranges): a. hemoglobin 1.5 x upper limit of normal (ULN) (benign hereditary hyperbilirubinemia, e.g. Gilbert’s syndrome is permitted), e. alanine aminotransferase (ALT) > 3 x ULN; if disease affecting the liver > 5 x ULN, f. aspartate aminotransferase (AST) > 3 x ULN; if disease affecting the liver > 5 x ULN, and g. serum creatinine increase (> 1.5 x ULN). 8. Patients with persistent Grade 3 or 4 toxicities (according to NCI-CTCAE v5.0) after prior treatments; toxicities must be resolved since at least 2 weeks before study treatment start to Grade 1 or less. However, alopecia or other persisting toxicities Grade = 2 not constituting a safety risk based on Investigator’s judgment are acceptable. 9. Active central nervous system (CNS) metastasis; patients with history of CNS metastases are eligible if CNS disease has been radiographically and neurologically stable for at least 6 weeks prior to ICF signing and do not require corticosteroids (of any dose; for the CNS disease specifically) for symptomatic management. 10. Other malignancy or prior malignancy with a disease-free interval of less than 3 years prior to ICF signing; except those treated with surgical intervention and an expected low likelihood of recurrence such as basal cell or squamous cell skin cancer, or carcinoma in situ, e.g. patients with adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ are eligible. 11. Patients with clinically significant active infection, cardiac disease, significant medical or psychiatric disease/condition that, in the opinion of the Investigator, would make the administration of study drug hazardous to the patient, interfere with the evaluation of study results, interpretation of patient safety, or prohibit patient understanding of the informed consent procedure or compliance with the requirements of the protocol – including (but not limited to): a. bacterial sepsis or similarly severe infections, b. uncontrolled or s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives are: Phase 1 to define the recommended phase 2 dose (RP2D) for EO2463 monotherapy, and to confirm the safety of EO2463 at the monotherapy RP2D in combination with lenalidomide (EL), rituximab (ER), and lenalidomide/rituximab (ER^2). Phase 2 to estimate the objective response rate (ORR) according to the Lugano Classification 2014 during EO2463 monotherapy ;Secondary Objective: The secondary objectives include assessment of: 1. safety and tolerability of EO2463 as monotherapy, and in combination with lenalidomide, rituximab, and lenalidomide/rituximab, for treatment of patients with FL and MZL, 2. changes (depletion/expansion), including durations, of B and T cell, and immunoglobulin levels, 3. immunogenicity in relation to T cells of OMP72, OMP64, OMP65, OMP66, and UCP2 that compose EO2463, including T cell cross-reactivity with the human B cell antigens CD20, CD22, CD37, and BAFF-receptor, 4. ORR and duration of response (DOR) by the Lugano Classification 2014, and the Lymphoma Response to Immunomodulatory Therapy Criteria (LyRIC) 2016 by trial cohort, and 5. time to next anti-lymphoma therapy (TTT), progression-free survival (PFS) and overall survival (OS) by trial cohort. ;Primary end point(s): The primary endpoints of the phase 1 part of the trial are to define the recommended phase 2 dose (RP2D) for EO2463 monotherapy by applying a 3-by-3 trial design and defined acceptability levels for safety concern events (Cohort 1), and to confirm the safety of EO2463 at the monotherapy RP2D in combination with lenalidomide (EL; Cohort 4), rituximab (ER; Cohort 2), and lenalidomide/rituximab (ER^2; Cohorts 1 and 4). The primary endpoint of the phase 2 part of the trial is to estimate the ORR according to the Lugano Classification, during EO2463 monotherapy (Cohort 1 weeks 1-6, Cohort 2 whole treatment period, and Cohort 3 weeks 1-6), among patients evaluable for efficacy (i.e. patients having at least one tumor assessment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The Secondary endpoints are: 1. Incidences of adverse events (AEs), treatment-emergent AEs (TEAEs), serious AEs (SAEs), deaths, treatment discontinuations/delays, and laboratory abnormalities using the NCI-CTCAE v5.0 grading system. For EO2463 administered as monotherapy, and in combination with lenalidomide, rituximab, and lenalidomide/rituximab. 2. Level of changes (depletion/expansion), including durations, of B and T cells, and immunoglobulins, as measured in peripheral blood (FACS) and serum (electrophoresis or equivalent method), respectively. 3. Percentage of patients with shown immunogenicity (expansion of specific T cells comparing samples taken at baseline versus on treatment in an individual patient determining if the patient has a positive response to the immunization, or not) in relation to OMP72, OMP64, OMP65, OMP66, and UCP2 that compose EO2463 by interferon-gamma (IFN-?) enzyme-linked immunospot (ELISpot), and by intracellular cytokines staining, and multimers staining assays. Cross reactivities with the human B cell antigens CD20, CD22, CD37, and BAFF-receptor will also be evaluated by the same methods. 4. ORR and DOR as described by the Lugano Classification 2014, and by the Lymphoma Response to Immunomodulatory Therapy Criteria (LyRIC) 2016 by trial cohort. 5. TTT, PFS and OS: a. TTT by trial cohort, defined as the time interval from the date of first study treatment administration to the date of start of the next (non-study treatment) systemic anti-lymphoma therapy. Patients who has not started a next (non-study treatment) systemic anti-lymphoma therapy will be censored at the date of the last documented follow-up. b. PFS as described by the Lugano Classification and LyRIC by trial cohort, defined as the time interval from the date of first study treatment administration to the date of progression, or death due to any cause, whichever is earlier. Patients without progression or death are to be censored at the time of the l | — |
Countries
France, Germany, Italy, Spain, United States
Contacts
Public ContactJan Fagerberg
Enterome
Outcome results
None listed