Clinical trial NCT05883449: Phase 2 Study of AFM13 in Combination with AB-101 in Subjects with R/R HL and CD30+ PTCL
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Relapsed or Refractory Hodgkin Lymphoma
Peripheral T Cell Lymphoma
Lead sponsor: Affimed GmbH
Sponsor class: INDUSTRY
Collaborators: name: Artiva Biotherapeutics, Inc.
First posted: 2023-06-01
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Objective Response Rate by Independent Radiology Committee
timeFrame: 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
Secondary outcomes:
measure: Duration of Response by Investigator and Independent Radiology Committee
timeFrame: 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)
measure: Complete response rate (CRR) by Investigator and Independent Radiology Committee
timeFrame: 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)
measure: ORR by Investigator based on PET-CT as assessed by the Lugano classification
timeFrame: 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)
measure: Incidence of subjects receiving subsequent transplant
timeFrame: Throughout study completion (estimated up to 24 months)
measure: Incidence of TEAEs and SAEs
timeFrame: From the time of first protocol-specific intervention until 30 days after the last administration
measure: Immunogenicity assessment of AFM13 in combination with AB-101
timeFrame: During treatment cycles (estimated up 6 months)
measure: Progression-free survival (PFS) by Independent Radiology Committee
timeFrame: Throughout study completion (estimated up to 24 months)
measure: Overall survival (OS)
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: O'Neal Comprehensive Cancer Center at UAB
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Orange
country: United States
facility: UC Irvine Health
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute
state: Colorado
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Beth Israel Deaconess Medical
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Immunotherapy Team, University of North Carolina at Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania, Abramson Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: Affimed Inc.
name: Wunderle Lydia, MD
role: STUDY_DIRECTOR
References: