Phase 1b/2, Open-Label Study to Evaluate Safety and Tolerability of Epcoritamab in Combination With Anti-Neoplastic Agents in Subjects With Non-Hodgkin Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- Genmab
- 入组人数
- 264
- 试验地点
- 147
- 主要终点
- Number of Participants with Dose-Limiting Toxicities (DLT)
研究概览
简要总结
B-cell Lymphoma is an aggressive and rare cancer of a type of immune cell (a white blood cell responsible for fighting infections). The purpose of this study is to assess the safety and tolerability of epcoritamab in combination with anti-neoplastic agents in adult participants with Non-Hodgkin lymphoma (NHL). Adverse events and change in disease activity will be assessed.
Epcoritamab is an investigational drug being developed for the treatment of NHL. Study doctors put the participants in groups called treatment arms. The combination of epcoritamab with anti-neoplastic agents will be explored. Each treatment arm receives a different treatment combination depending on eligibility. Approximately 496 adult participants with NHL will be enrolled in 100 sites globally.
In both the dose escalation and dose expansion arms participants will receive subcutaneous (SC) epcoritamab in 28 day, 21 day, or 56 day cycles dependent on the arm in combination with the anti-neoplastic agents described below:
1: Oral lenalidomide in participants (PPTS) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL); 2: Oral ibrutinib and oral lenalidomide in PPTS with R/R DLBCL; 3: Intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in PPTS with newly diagnosed treatment-naïve DLBCL, or completion of treatment in 3B; 4: Oral CC-99282 in PPTS with R/R DLBCL; 5: Oral CC-99282 in PPTS with R/R follicular lymphoma (FL); 6A: Oral ibrutinib in PPTS with R/R mantle cell lymphoma (MCL).
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.
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
- •Diagnosis of:
- •-- Diffuse large B-cell lymphoma (DLBCL) (de novo or histologically transformed from follicular lymphoma (FL) or nodal marginal zone lymphoma) with histologically confirmed CD20+ disease, inclusive of the following according to World Health Organization (WHO) 2016 classification and documented in pathology report:
- •DLBCL, not otherwise specified (NOS).
- •High-grade B cell lymphoma with MYC and BCL-2 and/or BCL-6 translocations per WHO 2016 ("double-hit" or "triple-hit") Note: High-grade B-cell lymphomas NOS or other double- /triple-hit lymphomas (with histologies not consistent with DLBCL) are not eligible.
- •Follicular lymphoma (FL) Grade 3B. OR
- •FL with histologically confirmed CD20+ Grade 1 to 3a and no evidence of histologic transformation to an aggressive lymphoma at most recent representative tumor biopsy, according to WHO 2016 classification. OR
- •Mantle cell lymphoma (MCL) with histologically confirmed CD20+ disease at most recent representative tumor biopsy according to the WHO 2016 classification with evidence of overexpression of cyclin D1 in association with relevant markers or evidence of t(11;14) assessed by flow cytometry, fluorescence in situ hybridization (FISH), or polymerase chain reaction (PCR).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2, except for Arm 6A where ECOG performance status must be 0-
- •Must have 1 or more measurable disease sites:
- •A positron emission tomography (PET) /computed tomography (CT) scan demonstrating PET-positive lesion(s) AND
- •At least 1 measurable nodal lesion (long axis > 1.5 cm) or >= 1 measurable extra-nodal lesion (long axis > 1.0 cm) on CT scan or magnetic resonance imaging (MRI).
排除标准
- •Prior treatment with epcoritamab or any other bispecific antibody targeting CD3 and CD
- •Toxicities from prior anticancer therapy that have not resolved to Common Terminology Criteria for Adverse Events (CTCAE, v 5.0), Grade 2 or below, with the exception of alopecia. Other eligibility criteria (e.g., laboratory, cardiac criteria) must also be met.
研究组 & 干预措施
Arm 1: Dose Expansion
Participants with R/R DLBCL will receive the recommended dose of epcoritamab in combination with lenalidomide in 28 day cycles.
干预措施: Epcoritamab (Drug)
Arm 2: Dose Expansion
Participants with R/R DLBCL will receive the recommended dose of epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles.
干预措施: Ibrutinib (Drug)
Arm 3: Dose Escalation
Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles.
干预措施: Epcoritamab (Drug)
Arm 3: Dose Escalation
Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles.
干预措施: Cyclophosphamide (Drug)
Arm 3: Dose Expansion
Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles.
干预措施: Polatuzumab Vedotin (Drug)
Arm 1: Dose Escalation
Participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) will receive escalating doses of epcoritamab in combination with lenalidomide in 28 day cycles.
干预措施: Lenalidomide (Drug)
Arm 5: Dose Escalation
Participants with R/R follicular lymphoma (FL) will receive escalating doses of epcoritamab in combination with CC-99282 in 28 day cycles.
干预措施: Epcoritamab (Drug)
Arm 3: Dose Expansion
Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles.
干预措施: Doxorubicin Hydrochloride [HCl] (Drug)
Arm 5: Dose Escalation
Participants with R/R follicular lymphoma (FL) will receive escalating doses of epcoritamab in combination with CC-99282 in 28 day cycles.
干预措施: CC-99282 (Drug)
Arm 3: Dose Escalation
Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles.
干预措施: Prednisone (Drug)
Arm 3: Dose Expansion
Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles.
干预措施: Prednisone (Drug)
Arm 3B: Dose Expansion
Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP), in 21 day cycles,until unacceptable toxicity, withdrawal of consent, or completion of treatment.
干预措施: Cyclophosphamide (Drug)
Arm 3: Dose Escalation
Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles.
干预措施: Rituximab (Drug)
Arm 2: Dose Escalation
Participants with R/R DLBCL will receive escalating doses of epcoritamab in combination with ibrutinib and lenalidomide in 28 day cycles.
干预措施: Epcoritamab (Drug)
Arm 6A: Dose Escalation
Participants with R/R mantle cell lymphoma (MCL) will receive escalating doses of epcoritamab in combination with ibrutinib in 28 day cycles.
干预措施: Epcoritamab (Drug)
Arm 3: Dose Escalation
Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles.
干预措施: Polatuzumab Vedotin (Drug)
Arm 2: Dose Escalation
Participants with R/R DLBCL will receive escalating doses of epcoritamab in combination with ibrutinib and lenalidomide in 28 day cycles.
干预措施: Lenalidomide (Drug)
Arm 2: Dose Expansion
Participants with R/R DLBCL will receive the recommended dose of epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles.
干预措施: Lenalidomide (Drug)
Arm 3: Dose Escalation
Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles.
干预措施: Doxorubicin Hydrochloride [HCl] (Drug)
Arm 2: Dose Escalation
Participants with R/R DLBCL will receive escalating doses of epcoritamab in combination with ibrutinib and lenalidomide in 28 day cycles.
干预措施: Ibrutinib (Drug)
Arm 6A: Dose Escalation
Participants with R/R mantle cell lymphoma (MCL) will receive escalating doses of epcoritamab in combination with ibrutinib in 28 day cycles.
干预措施: Ibrutinib (Drug)
Arm 3: Dose Expansion
Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles.
干预措施: Rituximab (Drug)
Arm 3B: Dose Expansion
Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP), in 21 day cycles,until unacceptable toxicity, withdrawal of consent, or completion of treatment.
干预措施: Polatuzumab Vedotin (Drug)
Arm 4: Dose Expansion
Participants with R/R DLBCL will receive the recommended dose of epcoritamab in combination with CC-99282 in 28 day cycles.
干预措施: Epcoritamab (Drug)
Arm 6: Dose Expansion
Participants with R/R MCL will receive the recommended dose of epcoritamab in combination with ibrutinib in 28 day cycles.
干预措施: Epcoritamab (Drug)
Arm 6: Dose Expansion
Participants with R/R MCL will receive the recommended dose of epcoritamab in combination with ibrutinib in 28 day cycles.
干预措施: Ibrutinib (Drug)
Arm 3B: Dose Expansion
Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP), in 21 day cycles,until unacceptable toxicity, withdrawal of consent, or completion of treatment.
干预措施: Doxorubicin Hydrochloride [HCl] (Drug)
Arm 5: Dose Expansion
Participants with R/R FL will receive the recommended dose of epcoritamab in combination with CC-99282 in 28 day cycles.
干预措施: CC-99282 (Drug)
Arm 4: Dose Expansion
Participants with R/R DLBCL will receive the recommended dose of epcoritamab in combination with CC-99282 in 28 day cycles.
干预措施: CC-99282 (Drug)
Arm 4: Dose Escalation
Participants with R/R DLBCL will receive escalating doses of epcoritamab in combination with CC-99282 in 28 day cycles.
干预措施: CC-99282 (Drug)
Arm 3B: Dose Expansion
Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP), in 21 day cycles,until unacceptable toxicity, withdrawal of consent, or completion of treatment.
干预措施: Epcoritamab (Drug)
Arm 3B: Dose Expansion
Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP), in 21 day cycles,until unacceptable toxicity, withdrawal of consent, or completion of treatment.
干预措施: Prednisone (Drug)
Arm 2: Dose Expansion
Participants with R/R DLBCL will receive the recommended dose of epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles.
干预措施: Epcoritamab (Drug)
Arm 1: Dose Expansion
Participants with R/R DLBCL will receive the recommended dose of epcoritamab in combination with lenalidomide in 28 day cycles.
干预措施: Lenalidomide (Drug)
Arm 3: Dose Expansion
Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles.
干预措施: Cyclophosphamide (Drug)
Arm 5: Dose Expansion
Participants with R/R FL will receive the recommended dose of epcoritamab in combination with CC-99282 in 28 day cycles.
干预措施: Epcoritamab (Drug)
Arm 3: Dose Expansion
Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles.
干预措施: Epcoritamab (Drug)
Arm 4: Dose Escalation
Participants with R/R DLBCL will receive escalating doses of epcoritamab in combination with CC-99282 in 28 day cycles.
干预措施: Epcoritamab (Drug)
Arm 3B: Dose Expansion
Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP), in 21 day cycles,until unacceptable toxicity, withdrawal of consent, or completion of treatment.
干预措施: Rituximab (Drug)
Arm 1: Dose Escalation
Participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) will receive escalating doses of epcoritamab in combination with lenalidomide in 28 day cycles.
干预措施: Epcoritamab (Drug)
结局指标
主要结局
Number of Participants with Dose-Limiting Toxicities (DLT)
时间窗: Up to Approximately 5 Years
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
次要结局
- Best Overall Response (BOR) per Investigator(Up to Approximately 5 Years)
- Duration of response (DOR) per Investigator(Up to Approximately 5 Years)
- Number of Participants with Progression-free survival (PFS)(Up to Approximately 5 Years)
- Percentage of Participants with Complete Response (CR)(Up to Approximately 5 Years)
- Time-to-response (TTR)(Up to Approximately 5 Years)
- Time to Next Antilymphoma Therapy (TTNT)(Up to Approximately 5 Years)
- Rate of Minimal Residual Disease (MRD) Negativity(Up to Approximately 5 Years)
- Overall Survival (OS)(Up to Approximately 5 Years)