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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Enterome
- 入组人数
- 80
- 试验地点
- 12
- 主要终点
- Phase 2: Overall Response Rate
研究概览
简要总结
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
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 EO
- •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.
研究组 & 干预措施
Cohort 1
Safety Lead-In, Dose-Finding, Cohort, with a 3-by-3 design of EO2463 monotherapy for 6 weeks followed by addition of lenalidomide. Then, if applicable rituximab (depending on response with EO2463 + lenalidomide) will be added. Four to 18 previously treated patients with Follicular Lymphoma (FL) or Marginal Zone Lymphoma (MZL) were anticipated to be included based on safety findings.
干预措施: EO2463 (Biological)
Cohort 1
Safety Lead-In, Dose-Finding, Cohort, with a 3-by-3 design of EO2463 monotherapy for 6 weeks followed by addition of lenalidomide. Then, if applicable rituximab (depending on response with EO2463 + lenalidomide) will be added. Four to 18 previously treated patients with Follicular Lymphoma (FL) or Marginal Zone Lymphoma (MZL) were anticipated to be included based on safety findings.
干预措施: lenalidomide (Drug)
Cohort 1
Safety Lead-In, Dose-Finding, Cohort, with a 3-by-3 design of EO2463 monotherapy for 6 weeks followed by addition of lenalidomide. Then, if applicable rituximab (depending on response with EO2463 + lenalidomide) will be added. Four to 18 previously treated patients with Follicular Lymphoma (FL) or Marginal Zone Lymphoma (MZL) were anticipated to be included based on safety findings.
干预措施: rituximab (Biological)
Cohort 2
Anticipated approximatively 25 previously untreated patients with FL or MZL with an evaluation of EO2463 monotherapy (at the established dose in Cohort 1).
干预措施: EO2463 (Biological)
Cohort 3
Anticipated approximatively 6 previously untreated patients with FL or MZL with an evaluation of EO2463 (at the established dose in cohort 1) as monotherapy for 6 weeks followed by addition of rituximab if applicable (depending on response with EO2463 monotherapy).
干预措施: EO2463 (Biological)
Cohort 3
Anticipated approximatively 6 previously untreated patients with FL or MZL with an evaluation of EO2463 (at the established dose in cohort 1) as monotherapy for 6 weeks followed by addition of rituximab if applicable (depending on response with EO2463 monotherapy).
干预措施: rituximab (Biological)
Cohort 4
Anticipated approximatively 40 patients previously treated patients with FL (or MZL). Evaluation of EO2463 (at the established dose in Cohort 1) in combination with lenalidomide from day 1 and then with addition of rituximab.
干预措施: EO2463 (Biological)
Cohort 4
Anticipated approximatively 40 patients previously treated patients with FL (or MZL). Evaluation of EO2463 (at the established dose in Cohort 1) in combination with lenalidomide from day 1 and then with addition of rituximab.
干预措施: lenalidomide (Drug)
Cohort 4
Anticipated approximatively 40 patients previously treated patients with FL (or MZL). Evaluation of EO2463 (at the established dose in Cohort 1) in combination with lenalidomide from day 1 and then with addition of rituximab.
干预措施: rituximab (Biological)
结局指标
主要结局
Phase 2: Overall Response Rate
时间窗: 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 |
时间窗: 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: Complete Response Rate
时间窗: Up to 24 months
Complete remission (CR)-rate according to the Lugano Classification 2014 during therapy with the combination of EO2463/lenalidomide/rituximab.
次要结局
- Evaluation of Overall Survival(Up to 7 years after last patient enrolled)
- Assessment of the Immunogenicity in Relation to OMP72, OMP64, OMP65, OMP66, and UCP2 that Compose EO2463(Up to 24 months)