Phase 2 Study of AFM13 in Combination With AB-101 in Subjects With R/R HL and CD30+ PTCL (LuminICE-203)

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

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.

Study Overview

• Status: Terminated
• Conditions: Peripheral T Cell Lymphoma; Relapsed or Refractory Hodgkin Lymphoma
• Intervention / Treatment: Drug: AFM13; Drug: AB-101; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2

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).

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • O'Neal Comprehensive Cancer Center at UAB
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Orange, California, United States, 92868
      • UC Irvine Health
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center, University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Immunotherapy Team, University of North Carolina at Chapel Hill
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania, Abramson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	Drug: AFM13; anti-human CD30 × anti-human CD16A recombinant antibody therapy, intravenous infusion; Drug: AB-101; NK cell therapy, intravenous infusion; Drug: Cyclophosphamide; Lymphodepleting chemotherapy, intravenous infusion; Drug: Fludarabine; Lymphodepleting chemotherapy, intravenous infusion; Drug: Interleukin-2; Immune cytokine, subcutaneously
Experimental: 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)	Drug: AFM13; anti-human CD30 × anti-human CD16A recombinant antibody therapy, intravenous infusion; Drug: AB-101; NK cell therapy, intravenous infusion; Drug: Cyclophosphamide; Lymphodepleting chemotherapy, intravenous infusion; Drug: Fludarabine; Lymphodepleting chemotherapy, intravenous infusion; Drug: Interleukin-2; Immune cytokine, subcutaneously
Experimental: 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)	Drug: AFM13; anti-human CD30 × anti-human CD16A recombinant antibody therapy, intravenous infusion; Drug: AB-101; NK cell therapy, intravenous infusion; Drug: Cyclophosphamide; Lymphodepleting chemotherapy, intravenous infusion; Drug: Fludarabine; Lymphodepleting chemotherapy, intravenous infusion; Drug: Interleukin-2; Immune cytokine, subcutaneously
Experimental: Exploratory: AFM13 + AB-101 on CD30-positive PTCL; AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B)	Drug: AFM13; anti-human CD30 × anti-human CD16A recombinant antibody therapy, intravenous infusion; Drug: AB-101; NK cell therapy, intravenous infusion; Drug: Cyclophosphamide; Lymphodepleting chemotherapy, intravenous infusion; Drug: Fludarabine; Lymphodepleting chemotherapy, intravenous infusion; Drug: Interleukin-2; Immune cytokine, subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) by Independent Radiology Committee	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.	Disease assessments were conducted on Day 43 (+- 3 days) of each cycle. All subjects were treated for a maximum of 3 cycles.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response by Independent Radiology Committee	Duration of response (DOR) defined as time from first assessment of PR or CR to the first assessment of progressive disease/death. Response based on positron emission tomography-computed tomography (PET-CT) as assessed by the Lugano classification assessed 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	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 20 months)
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 20 months)
Duration of Response by Investigator	Duration of response (DOR) defined as time from first assessment of PR or CR to the first assessment of progressive disease/death. Response based on positron emission tomography-computed tomography (PET-CT) as assessed by the Lugano classification assessed locally by the 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)
Incidence of Subjects Receiving Subsequent Transplant	The number of subjects receiving subsequent transplant will be assessed and summarized by percentage rates	Throughout study completion (up to 20 months)
Frequency of Subjects With Study Drug Related TEAEs	The number of subjects with study-drug related (AFM13 or AB-101) treatment-emergent adverse events (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	The number of subjects who had serious treatment emergent adverse events.	From the time of first protocol-specific intervention until 30 days after the last administration (up to 20 months)
Frequency of Subjects Developing Anti-drug Antibodies (ADAs) Against AFM13	The number of subjects developing anti-drug antibodies (ADAs) against AFM13	During treatment cycles (up to 6 months)
Progression-free Survival (PFS) by Independent Radiology Committee	Progression-free survival (PFS) defined as time from first treatment (AFM13/AB-101) received until progressive disease (PD). Subjects who started a new anti-lymphoma therapy prior to a documented progressive disease were censored at the last disease assessment prior to initiation of new anti-lymphoma therapy. Subjects who discontinued the study before the first assessment of progressive disease or death were censored at their last disease assessment.	From the first treatment received until the first progression disease assessed by IRC or death.
Overall Survival	Overall Survival (OS) was defined as (date of death - date of first dose)/30.4375. Patients alive at the end of study will be censored on the last date of observation.	From the first treatment received until the death.

Collaborators and Investigators

• Sponsor: Affimed GmbH
• Collaborators: Artiva Biotherapeutics, Inc.
• Investigators: Study Director: Wunderle Lydia, MD, Affimed Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2023
• Primary Completion (Actual): November 7, 2024
• Study Completion (Actual): June 13, 2025

Study Registration Dates

• First Submitted: May 19, 2023
• First Submitted That Met QC Criteria: May 30, 2023
• First Posted (Actual): June 1, 2023

Study Record Updates

• Last Update Posted (Actual): August 20, 2025
• Last Update Submitted That Met QC Criteria: August 12, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hodgkin Disease; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine; Interleukin-2
• Other Study ID Numbers: AFM13-203

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No