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

Affimed

Status and phase: Terminated; Phase 2

Conditions: Relapsed or Refractory Hodgkin Lymphoma; Peripheral T Cell Lymphoma

Treatments: Drug: Interleukin-2; Drug: AB-101; Drug: AFM13; Drug: Fludarabine; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT05883449

AFM13-203

Details and patient eligibility

About

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.

Full 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).

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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25 participants in 4 patient groups

Safety run-in in Hodgkin Lymphoma

Experimental group

Description:

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)

Treatment:

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: AFM13

Drug: AB-101

Drug: Interleukin-2

Dose Level A in Hodgkin Lymphoma

Experimental group

Description:

Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level A (selected from cohort 1-4 of Safety run-in)

Treatment:

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: AFM13

Drug: AB-101

Drug: Interleukin-2

Dose Level B in Hodgkin Lymphoma

Experimental group

Description:

Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level B (selected from cohort 1-4 of Safety run-in)

Treatment:

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: AFM13

Drug: AB-101

Drug: Interleukin-2

Exploratory: AFM13 + AB-101 on CD30-positive PTCL

Experimental group

Description:

AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B)

Treatment:

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: AFM13

Drug: AB-101

Drug: Interleukin-2