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

Sponsor

Affimed GmbH (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05883449

Collaborator

Artiva Biotherapeutics, Inc. (Industry)

154

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Hodgkin Lymphoma Peripheral T Cell Lymphoma	Drug: AFM13 Drug: AB-101 Drug: Cyclophosphamide Drug: Fludarabine Drug: Interleukin-2	Phase 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 Design

Study Type:

Interventional

Anticipated Enrollment :

154 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jul 31, 2023

Anticipated Primary Completion Date :

Apr 30, 2026

Anticipated Study Completion Date :

Nov 30, 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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