Phase 2 Study of AFM13 in Combination with AB-101 in Subjects with R/R HL and CD30+ PTCL
- Conditions
- Relapsed or Refractory Hodgkin LymphomaPeripheral T Cell Lymphoma
- Interventions
- Registration Number
- NCT05883449
- Lead Sponsor
- Affimed GmbH
- Brief Summary
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.
- Detailed Description
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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 154
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Exploratory: AFM13 + AB-101 on CD30-positive PTCL Interleukin-2 AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B) Safety run-in in Hodgkin Lymphoma AFM13 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) Safety run-in in Hodgkin Lymphoma AB-101 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) Safety run-in in Hodgkin Lymphoma Interleukin-2 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) Dose Level A in Hodgkin Lymphoma AFM13 Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level A (selected from cohort 1-4 of Safety run-in) Dose Level A in Hodgkin Lymphoma AB-101 Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level A (selected from cohort 1-4 of Safety run-in) Dose Level B in Hodgkin Lymphoma AFM13 Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level B (selected from cohort 1-4 of Safety run-in) Dose Level B in Hodgkin Lymphoma AB-101 Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level B (selected from cohort 1-4 of Safety run-in) Exploratory: AFM13 + AB-101 on CD30-positive PTCL AFM13 AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B) Exploratory: AFM13 + AB-101 on CD30-positive PTCL AB-101 AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B) Safety run-in in Hodgkin Lymphoma Cyclophosphamide 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) Safety run-in in Hodgkin Lymphoma Fludarabine 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) Dose Level A in Hodgkin Lymphoma Cyclophosphamide Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level A (selected from cohort 1-4 of Safety run-in) Dose Level A in Hodgkin Lymphoma Fludarabine Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level A (selected from cohort 1-4 of Safety run-in) Dose Level A in Hodgkin Lymphoma Interleukin-2 Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level A (selected from cohort 1-4 of Safety run-in) Dose Level B in Hodgkin Lymphoma Cyclophosphamide Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level B (selected from cohort 1-4 of Safety run-in) Dose Level B in Hodgkin Lymphoma Interleukin-2 Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level B (selected from cohort 1-4 of Safety run-in) Dose Level B in Hodgkin Lymphoma Fludarabine Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level B (selected from cohort 1-4 of Safety run-in) Exploratory: AFM13 + AB-101 on CD30-positive PTCL Cyclophosphamide AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B) Exploratory: AFM13 + AB-101 on CD30-positive PTCL Fludarabine AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B)
- Primary Outcome Measures
Name Time Method Objective Response Rate by Independent Radiology Committee From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months 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
- Secondary Outcome Measures
Name Time Method Duration of Response by Investigator and 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 24 months) Duration of response (DOR) defined as time from first assessment of PR or CR to the first assessment of progressive disease. Response based on positron emission tomography-computed tomography (PET-CT) as assessed by the Lugano classification.
Complete response rate (CRR) by Investigator and 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 24 months) Complete Response Rate based on positron emission tomography-computed tomography (PET-CT) as assessed by the Lugano classification.
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 24 months) ORR (CR + PR) by Investigator based on positron emission tomography-computed tomography (PET-CT) as assessed by the Lugano classification
Incidence of subjects receiving subsequent transplant Throughout study completion (estimated up to 24 months) The incidence of subjects receiving subsequent transplant will be assessed and summarized by percentage rates and 95% Confidence Intervals
Incidence of TEAEs and SAEs From the time of first protocol-specific intervention until 30 days after the last administration Frequency of subjects with study-drug related treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Immunogenicity assessment of AFM13 in combination with AB-101 During treatment cycles (estimated up 6 months) Frequency of subjects developing anti-drug antibodies (ADAs) against AFM13 or AB-101
Progression-free survival (PFS) by Independent Radiology Committee Throughout study completion (estimated up to 24 months) Progression-free survival (PFS) defined as time from first treatment (AFM13/AB-101) received until PD/OS.
Overall survival (OS) up to 24 months Overall survival rate
Trial Locations
- Locations (15)
UNC Immunotherapy Team, University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
O'Neal Comprehensive Cancer Center at UAB
🇺🇸Birmingham, Alabama, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
UC Irvine Health
🇺🇸Orange, California, United States
Sarah Cannon Research Institute
🇺🇸Denver, Colorado, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Beth Israel Deaconess Medical
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Masonic Cancer Center, University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
John Theurer Cancer Center
🇺🇸Hackensack, New Jersey, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University of Pennsylvania, Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States