Peripheral T Cell Lymphoma, Relapsed or Refractory Hodgkin Lymphoma
Conditions
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).
Interventions
DRUGAFM13
anti-human CD30 × anti-human CD16A recombinant antibody therapy, intravenous infusion
DRUGAB-101
NK cell therapy, intravenous infusion
DRUGCyclophosphamide
Lymphodepleting chemotherapy, intravenous infusion
DRUGFludarabine
Lymphodepleting chemotherapy, intravenous infusion
DRUGInterleukin-2
Immune cytokine, subcutaneously
Sponsors
Artiva Biotherapeutics, Inc.
Affimed GmbH
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) by Independent Radiology Committee | Disease assessments were conducted on Day 43 (+- 3 days) of each cycle. All subjects were treated for a maximum of 3 cycles. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (CRR) 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 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 20 months) | ORR (CR + PR) by Investigator based on positron emission tomography-computed tomography (PET-CT) as assessed by the Lugano classification |
| Duration of Response by 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) | 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. |
| Incidence of Subjects Receiving Subsequent Transplant | Throughout study completion (up to 20 months) | The number of subjects receiving subsequent transplant will be assessed and summarized by percentage rates |
| Duration of Response 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) | 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. |
| Frequency of Subjects With Serious Treatment Emergent Adverse Events | From the time of first protocol-specific intervention until 30 days after the last administration (up to 20 months) | The number of subjects who had serious treatment emergent adverse events. |
| Frequency of Subjects Developing Anti-drug Antibodies (ADAs) Against AFM13 | During treatment cycles (up to 6 months) | The number of subjects developing anti-drug antibodies (ADAs) against AFM13 |
| Progression-free Survival (PFS) by Independent Radiology Committee | From the first treatment received until the first progression disease assessed by IRC or death. | 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. |
| Overall Survival | From the first treatment received until the death. | 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. |
| Frequency of Subjects With Study Drug Related TEAEs | From the time of first protocol-specific intervention until 30 days after the last administration (up to 20 months) | The number of subjects with study-drug related (AFM13 or AB-101) treatment-emergent adverse events (TEAEs) |
Countries
United States
Participant flow
Pre-assignment details
The three experimental Arms/Groups: 'Dose Level A in Hodgin Lymphoma', 'Dose Level B in Hodgin Lymphoma' and 'Exploratory: AFM13 + AB-101 on CD30-positive PTCL' were not enrolled due to the decision to terminate this study earlier, which was based solely on the financial situation of the company and was not related to the safety or efficacy.
Participants by arm
| Arm | Count |
|---|---|
| Safety run-in Cohort 1 Cohort 1: 200 mg AFM13 + AB-101 (2 × 10e9 cells on Day 1, Day 8, Day 15)
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 | 6 |
| Safety run-in Cohort 2 Cohort 2: 300 mg AFM13 + AB-101 (2 × 10e9 cells on Day 1, Day 8, Day 15)
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 | 7 |
| Safety run-in Cohort 3 Cohort 3: 200 mg AFM13 + AB-101 (4 × 10e9 cells on Day 1; 2 × 10e9 cells on Day 8, Day 15)
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 | 6 |
| Safety run-in Cohort 4 Cohort 4: 300 mg AFM13 + AB-101 (4 × 10e9 cells on Day 1; 2 × 10e9 cells on Day 8, Day 15)
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 | 6 |
| Total | 25 |
Baseline characteristics
| Characteristic | Safety run-in Cohort 1 | Total | Safety run-in Cohort 4 | Safety run-in Cohort 3 | Safety run-in Cohort 2 |
|---|---|---|---|---|---|
| Age, Continuous | 50.5 years STANDARD_DEVIATION 20.68 | 48.5 years STANDARD_DEVIATION 18.07 | 46.0 years STANDARD_DEVIATION 19.8 | 54.7 years STANDARD_DEVIATION 14.61 | 43.6 years STANDARD_DEVIATION 19.21 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 23 Participants | 5 Participants | 5 Participants | 7 Participants |
| Region of Enrollment United States | 6 participants | 25 participants | 6 participants | 6 participants | 7 participants |
| Sex: Female, Male Female | 3 Participants | 17 Participants | 4 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 8 Participants | 2 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 6 | 4 / 7 | 1 / 6 | 0 / 6 |
| other Total, other adverse events | 6 / 6 | 7 / 7 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 2 / 6 | 5 / 7 | 4 / 6 | 5 / 6 |
Outcome results
Primary
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.
Time frame: Disease assessments were conducted on Day 43 (+- 3 days) of each cycle. All subjects were treated for a maximum of 3 cycles.
Population: The Safety Run In Set (SRI) consists of all subjects of the 4 safety run-in cohorts who have received at least 66% of the combination dose during Cycle 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety run-in Cohort 1 | Objective Response Rate (ORR) by Independent Radiology Committee | 5 Participants |
| Safety run-in Cohort 2 | Objective Response Rate (ORR) by Independent Radiology Committee | 5 Participants |
| Safety run-in Cohort 3 | Objective Response Rate (ORR) by Independent Radiology Committee | 6 Participants |
| Safety run-in Cohort 4 | Objective Response Rate (ORR) by Independent Radiology Committee | 5 Participants |
Secondary
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.
Time frame: 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)
Population: The Safety Run In Set (SRI) consists of all subjects of the 4 safety run-in cohorts who have received at least 66% of the combination dose during Cycle 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety run-in Cohort 1 | Complete Response Rate (CRR) by Independent Radiology Committee | 4 Participants |
| Safety run-in Cohort 2 | Complete Response Rate (CRR) by Independent Radiology Committee | 3 Participants |
| Safety run-in Cohort 3 | Complete Response Rate (CRR) by Independent Radiology Committee | 4 Participants |
| Safety run-in Cohort 4 | Complete Response Rate (CRR) by Independent Radiology Committee | 3 Participants |
Secondary
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.
Time frame: 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)
Population: All patients in the Safety Run In Set who had a response (CR or PR) assessed by the independent review committee.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Safety run-in Cohort 1 | Duration of Response by Independent Radiology Committee | 4.90 months |
| Safety run-in Cohort 2 | Duration of Response by Independent Radiology Committee | NA months |
| Safety run-in Cohort 3 | Duration of Response by Independent Radiology Committee | NA months |
| Safety run-in Cohort 4 | Duration of Response by Independent Radiology Committee | 6.97 months |
Secondary
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.
Time frame: 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)
Population: All patients in the Safety Run In Set who had a response (CR or PR) assessed by the investigator.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Safety run-in Cohort 1 | Duration of Response by Investigator | 3.86 months |
| Safety run-in Cohort 2 | Duration of Response by Investigator | 6.28 months |
| Safety run-in Cohort 3 | Duration of Response by Investigator | NA months |
| Safety run-in Cohort 4 | Duration of Response by Investigator | 4.65 months |
Secondary
Frequency of Subjects Developing Anti-drug Antibodies (ADAs) Against AFM13
The number of subjects developing anti-drug antibodies (ADAs) against AFM13
Time frame: During treatment cycles (up to 6 months)
Population: The safety analysis set (SAS) will consist of all subjects who received any amount of any component of the regimen.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety run-in Cohort 1 | Frequency of Subjects Developing Anti-drug Antibodies (ADAs) Against AFM13 | 2 Participants |
| Safety run-in Cohort 2 | Frequency of Subjects Developing Anti-drug Antibodies (ADAs) Against AFM13 | 1 Participants |
| Safety run-in Cohort 3 | Frequency of Subjects Developing Anti-drug Antibodies (ADAs) Against AFM13 | 2 Participants |
| Safety run-in Cohort 4 | Frequency of Subjects Developing Anti-drug Antibodies (ADAs) Against AFM13 | 1 Participants |
Secondary
Frequency of Subjects With Serious Treatment Emergent Adverse Events
The number of subjects who had serious treatment emergent adverse events.
Time frame: From the time of first protocol-specific intervention until 30 days after the last administration (up to 20 months)
Population: The safety analysis set (SAS) will consist of all subjects who received any amount of any component of the regimen.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety run-in Cohort 1 | Frequency of Subjects With Serious Treatment Emergent Adverse Events | 2 Participants |
| Safety run-in Cohort 2 | Frequency of Subjects With Serious Treatment Emergent Adverse Events | 5 Participants |
| Safety run-in Cohort 3 | Frequency of Subjects With Serious Treatment Emergent Adverse Events | 4 Participants |
| Safety run-in Cohort 4 | Frequency of Subjects With Serious Treatment Emergent Adverse Events | 5 Participants |
Secondary
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)
Time frame: From the time of first protocol-specific intervention until 30 days after the last administration (up to 20 months)
Population: The safety analysis set (SAS) will consist of all subjects who received any amount of any component of the regimen.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety run-in Cohort 1 | Frequency of Subjects With Study Drug Related TEAEs | 5 Participants |
| Safety run-in Cohort 2 | Frequency of Subjects With Study Drug Related TEAEs | 4 Participants |
| Safety run-in Cohort 3 | Frequency of Subjects With Study Drug Related TEAEs | 5 Participants |
| Safety run-in Cohort 4 | Frequency of Subjects With Study Drug Related TEAEs | 5 Participants |
Secondary
Incidence of Subjects Receiving Subsequent Transplant
The number of subjects receiving subsequent transplant will be assessed and summarized by percentage rates
Time frame: Throughout study completion (up to 20 months)
Population: The Safety Run In Set (SRI) consists of all subjects of the 4 safety run-in cohorts who have received at least 66% of the combination dose during Cycle 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety run-in Cohort 1 | Incidence of Subjects Receiving Subsequent Transplant | 1 Participants |
| Safety run-in Cohort 2 | Incidence of Subjects Receiving Subsequent Transplant | 2 Participants |
| Safety run-in Cohort 3 | Incidence of Subjects Receiving Subsequent Transplant | 0 Participants |
| Safety run-in Cohort 4 | Incidence of Subjects Receiving Subsequent Transplant | 1 Participants |
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
Time frame: 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)
Population: The Safety Run In Set (SRI) consists of all subjects of the 4 safety run-in cohorts who have received at least 66% of the combination dose during Cycle 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety run-in Cohort 1 | ORR by Investigator Based on PET-CT as Assessed by the Lugano Classification | 4 Participants |
| Safety run-in Cohort 2 | ORR by Investigator Based on PET-CT as Assessed by the Lugano Classification | 5 Participants |
| Safety run-in Cohort 3 | ORR by Investigator Based on PET-CT as Assessed by the Lugano Classification | 6 Participants |
| Safety run-in Cohort 4 | ORR by Investigator Based on PET-CT as Assessed by the Lugano Classification | 6 Participants |
Secondary
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.
Time frame: From the first treatment received until the death.
Population: The Safety Run In Set (SRI) consists of all subjects of the 4 safety run-in cohorts who have received at least 66% of the combination dose during Cycle 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Safety run-in Cohort 1 | Overall Survival | NA months |
| Safety run-in Cohort 2 | Overall Survival | 12.25 months |
| Safety run-in Cohort 3 | Overall Survival | 9.72 months |
| Safety run-in Cohort 4 | Overall Survival | NA 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 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.
Time frame: From the first treatment received until the first progression disease assessed by IRC or death.
Population: The Safety Run In Set (SRI) consists of all subjects of the 4 safety run-in cohorts who have received at least 66% of the combination dose during Cycle 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Safety run-in Cohort 1 | Progression-free Survival (PFS) by Independent Radiology Committee | 4.17 months |
| Safety run-in Cohort 2 | Progression-free Survival (PFS) by Independent Radiology Committee | 7.66 months |
| Safety run-in Cohort 3 | Progression-free Survival (PFS) by Independent Radiology Committee | NA months |
| Safety run-in Cohort 4 | Progression-free Survival (PFS) by Independent Radiology Committee | 8.28 months |