Phase 2 Study of AFM13 in Combination With AB-101 in Subjects With R/R HL and CD30+ PTCL

Peripheral T Cell Lymphoma Clinical Trial

— LuminICE-203  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05883449
• Other study ID #: AFM13-203
• Status: Recruiting
• Phase: Phase 2
• Start date: October 10, 2023
• Est. completion date: November 30, 2027

Study information

• Verified date: April 2024
• Source: Affimed GmbH
• Contact: Affimed GmbH
• Phone: 004962216743
• Email: trials[@]affimed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 154
• Est. completion date: November 30, 2027
• Est. primary completion date: April 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T Cell Lymphoma
• Relapsed or Refractory Hodgkin Lymphoma

Intervention

Drug:
• AFM13
anti-human CD30 × anti-human CD16A recombinant antibody therapy, intravenous infusion
• AB-101
NK cell therapy, intravenous infusion
• Cyclophosphamide
Lymphodepleting chemotherapy, intravenous infusion
• Fludarabine
Lymphodepleting chemotherapy, intravenous infusion
• Interleukin-2
Immune cytokine, subcutaneously

Locations

Country	Name	City	State
United States	O'Neal Comprehensive Cancer Center at UAB	Birmingham	Alabama
United States	Cleveland Clinic	Cleveland	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	John Theurer Cancer Center	Hackensack	New Jersey
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	UC Irvine Health	Orange	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Affimed GmbH	Artiva Biotherapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate by Independent Radiology Committee	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	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	Duration of Response by Investigator and Independent Radiology Committee	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.	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)
Secondary	Complete response rate (CRR) by Investigator and Independent Radiology Committee	Complete Response Rate based on positron emission tomography-computed tomography (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)
Secondary	ORR by Investigator based on PET-CT as assessed by the Lugano classification	ORR (CR + PR) by Investigator based on positron emission tomography-computed tomography (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)
Secondary	Incidence of subjects receiving subsequent transplant	The incidence of subjects receiving subsequent transplant will be assessed and summarized by percentage rates and 95% Confidence Intervals	Throughout study completion (estimated up to 24 months)
Secondary	Incidence of TEAEs and SAEs	Frequency of subjects with study-drug related treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	From the time of first protocol-specific intervention until 30 days after the last administration
Secondary	Immunogenicity assessment of AFM13 in combination with AB-101	Frequency of subjects developing anti-drug antibodies (ADAs) against AFM13 or AB-101	During treatment cycles (estimated up 6 months)
Secondary	Progression-free survival (PFS) by Independent Radiology Committee	Progression-free survival (PFS) defined as time from first treatment (AFM13/AB-101) received until PD/OS.	Throughout study completion (estimated up to 24 months)
Secondary	Overall survival (OS)	Overall survival rate	up to 24 months