A Phase 2, Open-Label, Multi-Center Study of Innate Cell Engager AFM13 in Combination With Allogeneic Natural Killer Cells (AB-101) in Subjects With Recurrent or Refractory Hodgkin Lymphoma and CD-30 Positive Peripheral T-Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Affimed GmbH
- 入组人数
- 25
- 试验地点
- 15
- 主要终点
- Objective Response Rate (ORR) by Independent Radiology Committee
研究概览
简要总结
AFM13-203 is a phase 2, open-label, multi-center, multi-cohort study with a safety run-in followed by expansion cohorts. The study is evaluating the safety and efficacy of AFM13 in combination with AB-101 in subjects with R/R classical HL and CD30-positive PTCL.
详细描述
The study will start with a safety run-in exploring AFM13/AB-101 combination treatment in subjects with classical HL. Two dose levels of AFM13 and AB-101, respectively, will be tested in 4 cohorts. Cohort 1 and 2 will enroll in parallel. Enrolment into Cohort 3 and 4 will start only if the combination treatment has been well tolerated.
Following the safety run-in observation period, a thorough risk-benefit analysis will be performed to determine 2 of the 4 cohorts/dose levels that will be further evaluated in the main part of the study which will also include subjects with classical HL and will follow a Simon two-stage design.
An additional exploratory cohort (Cohort 5) will enroll subjects with select CD30-positive PTCL subtypes after completion of the safety run-in.
All subjects will be treated with AFM13/AB-101 for a maximum of 3 cycles (cycle length is 48-days).
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Subjects with a diagnosis of FDG-avid relapsed or refractory classical HL OR select subtypes of FDG-avid CD30-positive relapsed or refractory PTCL
- •For subjects with R/R PTCL a pre-enrollment tumor biopsy positive for CD30 locally assessed by Ber-H2 targeted immunohistochemistry at ≥1% is mandatory (PTCL subtypes: PTCL-NOS, Angioimmunoblastic T-cell lymphoma, ALCL, anaplastic lymphoma kinase (ALK)-positive, ALCL, ALK-negative)
- •Subjects with R/R classical HL must have received at least two lines of therapy including one prior line of combination chemotherapy. Prior therapy must also have included brentuximab vedotin and a PD1 check point inhibitor.
- •Subjects with R/R PTCL must have received at least one prior line of combination chemotherapy. Subjects with ALCL subtype of PTCL must have received or been intolerant to brentuximab vedotin.
- •Subjects with R/R classical HL AND R/R PTCL: Prior ASCT is permitted if completed at least 3 months prior to the first dose of study treatment. Prior allogeneic stem cell transplantation will be permitted if completed at least 1 year from study enrollment and there are no signs or symptoms of GVHD. Prior CAR-T therapy is permitted if last CAR-T dose completed at least 6 months prior to the first dose of study treatment.
- •Ability to understand and sign the ICF
排除标准
- •Active central nervous system (CNS) involvement (untreated or uncontrolled parenchymal brain metastasis or positive cytology of cerebrospinal fluid)
- •Previous treatment with AFM13 or CBNK cells
- •History of a solid organ allograft, or an inflammatory or autoimmune disease likely to be exacerbated by IL-2 (including subjects requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease that may require systemic steroids or immunosuppressive agents
- •Treatment with any therapeutic mAb or immunosuppressive medications
- •Known active Hepatitis B or C defined per protocol
- •Active HIV Infection
- •History of any other systemic malignancy, unless previously treated with curative intent and the subject has been disease free for 2 years or longer
- •Active acute or chronic graft vs. host disease (GVHD) or GVHD requiring immunosuppressive treatment, clinically significant central nervous system (CNS) dysfunction
研究组 & 干预措施
Dose Level B in Hodgkin Lymphoma
Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level B (selected from cohort 1-4 of Safety run-in)
干预措施: Fludarabine (Drug)
Safety run-in in Hodgkin Lymphoma
4 safety run-in cohorts:
- Cohort 1: 200 mg AFM13 + AB-101 (2 × 10e9 cells on Day 1, Day 8, Day 15)
- Cohort 2: 300 mg AFM13 + AB-101 (2 × 10e9 cells on Day 1, Day 8, Day 15)
- Cohort 3: 200 mg AFM13 + AB-101 (4 × 10e9 cells on Day 1; 2 × 10e9 cells on Day 8, Day 15)
- Cohort 4: 300 mg AFM13 + AB-101 (4 × 10e9 cells on Day 1; 2 × 10e9 cells on Day 8, Day 15)
干预措施: AFM13 (Drug)
Safety run-in in Hodgkin Lymphoma
4 safety run-in cohorts:
- Cohort 1: 200 mg AFM13 + AB-101 (2 × 10e9 cells on Day 1, Day 8, Day 15)
- Cohort 2: 300 mg AFM13 + AB-101 (2 × 10e9 cells on Day 1, Day 8, Day 15)
- Cohort 3: 200 mg AFM13 + AB-101 (4 × 10e9 cells on Day 1; 2 × 10e9 cells on Day 8, Day 15)
- Cohort 4: 300 mg AFM13 + AB-101 (4 × 10e9 cells on Day 1; 2 × 10e9 cells on Day 8, Day 15)
干预措施: AB-101 (Drug)
Safety run-in in Hodgkin Lymphoma
4 safety run-in cohorts:
- Cohort 1: 200 mg AFM13 + AB-101 (2 × 10e9 cells on Day 1, Day 8, Day 15)
- Cohort 2: 300 mg AFM13 + AB-101 (2 × 10e9 cells on Day 1, Day 8, Day 15)
- Cohort 3: 200 mg AFM13 + AB-101 (4 × 10e9 cells on Day 1; 2 × 10e9 cells on Day 8, Day 15)
- Cohort 4: 300 mg AFM13 + AB-101 (4 × 10e9 cells on Day 1; 2 × 10e9 cells on Day 8, Day 15)
干预措施: Cyclophosphamide (Drug)
Safety run-in in Hodgkin Lymphoma
4 safety run-in cohorts:
- Cohort 1: 200 mg AFM13 + AB-101 (2 × 10e9 cells on Day 1, Day 8, Day 15)
- Cohort 2: 300 mg AFM13 + AB-101 (2 × 10e9 cells on Day 1, Day 8, Day 15)
- Cohort 3: 200 mg AFM13 + AB-101 (4 × 10e9 cells on Day 1; 2 × 10e9 cells on Day 8, Day 15)
- Cohort 4: 300 mg AFM13 + AB-101 (4 × 10e9 cells on Day 1; 2 × 10e9 cells on Day 8, Day 15)
干预措施: Fludarabine (Drug)
Safety run-in in Hodgkin Lymphoma
4 safety run-in cohorts:
- Cohort 1: 200 mg AFM13 + AB-101 (2 × 10e9 cells on Day 1, Day 8, Day 15)
- Cohort 2: 300 mg AFM13 + AB-101 (2 × 10e9 cells on Day 1, Day 8, Day 15)
- Cohort 3: 200 mg AFM13 + AB-101 (4 × 10e9 cells on Day 1; 2 × 10e9 cells on Day 8, Day 15)
- Cohort 4: 300 mg AFM13 + AB-101 (4 × 10e9 cells on Day 1; 2 × 10e9 cells on Day 8, Day 15)
干预措施: Interleukin-2 (Drug)
Dose Level B in Hodgkin Lymphoma
Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level B (selected from cohort 1-4 of Safety run-in)
干预措施: Cyclophosphamide (Drug)
Dose Level A in Hodgkin Lymphoma
Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level A (selected from cohort 1-4 of Safety run-in)
干预措施: AFM13 (Drug)
Dose Level A in Hodgkin Lymphoma
Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level A (selected from cohort 1-4 of Safety run-in)
干预措施: AB-101 (Drug)
Dose Level A in Hodgkin Lymphoma
Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level A (selected from cohort 1-4 of Safety run-in)
干预措施: Cyclophosphamide (Drug)
Dose Level A in Hodgkin Lymphoma
Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level A (selected from cohort 1-4 of Safety run-in)
干预措施: Fludarabine (Drug)
Dose Level A in Hodgkin Lymphoma
Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level A (selected from cohort 1-4 of Safety run-in)
干预措施: Interleukin-2 (Drug)
Dose Level B in Hodgkin Lymphoma
Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level B (selected from cohort 1-4 of Safety run-in)
干预措施: AFM13 (Drug)
Dose Level B in Hodgkin Lymphoma
Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level B (selected from cohort 1-4 of Safety run-in)
干预措施: AB-101 (Drug)
Dose Level B in Hodgkin Lymphoma
Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level B (selected from cohort 1-4 of Safety run-in)
干预措施: Interleukin-2 (Drug)
Exploratory: AFM13 + AB-101 on CD30-positive PTCL
AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B)
干预措施: AFM13 (Drug)
Exploratory: AFM13 + AB-101 on CD30-positive PTCL
AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B)
干预措施: AB-101 (Drug)
Exploratory: AFM13 + AB-101 on CD30-positive PTCL
AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B)
干预措施: Cyclophosphamide (Drug)
Exploratory: AFM13 + AB-101 on CD30-positive PTCL
AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B)
干预措施: Fludarabine (Drug)
Exploratory: AFM13 + AB-101 on CD30-positive PTCL
AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B)
干预措施: Interleukin-2 (Drug)
结局指标
主要结局
Objective Response Rate (ORR) by Independent Radiology Committee
时间窗: Disease assessments were conducted on Day 43 (+- 3 days) of each cycle. All subjects were treated for a maximum of 3 cycles.
Best ORR (complete response (CR) + partial response \[PR\]) by Independent Radiology Committee (IRC) based on positron emission tomography-computed tomography (PET-CT) as assessed by the Lugano classification. A participant will be assumed as a responder if he/she achieves complete or partial response at any postbaseline visit.
次要结局
- Duration of Response by Independent Radiology Committee(Tumor assessment performed every 6 weeks for 3 cycles, if no disease progression on completion of treatment, then every 3 months for the first 12 months and then every 6 months (up to 20 months))
- Complete Response Rate (CRR) by Independent Radiology Committee(Tumor assessment performed every 6 weeks for 3 cycles, if no disease progression on completion of treatment, then every 3 months for the first 12 months and then every 6 months (up to 20 months))
- Duration of Response by Investigator(Tumor assessment performed every 6 weeks for 3 cycles, if no disease progression on completion of treatment, then every 3 months for the first 12 months and then every 6 months (up to 20 months))
- Frequency of Subjects Developing Anti-drug Antibodies (ADAs) Against AFM13(During treatment cycles (up to 6 months))
- ORR by Investigator Based on PET-CT as Assessed by the Lugano Classification(Tumor assessment performed every 6 weeks for 3 cycles, if no disease progression on completion of treatment, then every 3 months for the first 12 months and then every 6 months (up to 20 months))
- Incidence of Subjects Receiving Subsequent Transplant(Throughout study completion (up to 20 months))
- Progression-free Survival (PFS) by Independent Radiology Committee(From the first treatment received until the first progression disease assessed by IRC or death.)
- Overall Survival(From the first treatment received until the death.)
- Frequency of Subjects With Study Drug Related TEAEs(From the time of first protocol-specific intervention until 30 days after the last administration (up to 20 months))
- Frequency of Subjects With Serious Treatment Emergent Adverse Events(From the time of first protocol-specific intervention until 30 days after the last administration (up to 20 months))