Clinical trial NCT05883449
Conditions: Relapsed or Refractory Hodgkin Lymphoma Peripheral T Cell Lymphoma
Sponsor: Affimed GmbH
Start date: 2023-10-10; Completion date: 2025-06-13
Enrollment: 25 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

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).

Arms: arm 1: 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) arm 2: Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level A (selected from cohort 1-4 of Safety run-in) arm 3: Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level B (selected from cohort 1-4 of Safety run-in) arm 4: AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B)
Interventions: intervention 1: AFM13 intervention 2: AB-101 intervention 3: Cyclophosphamide intervention 4: Fludarabine intervention 5: Interleukin-2
Intervention descriptions: intervention 1: anti-human CD30 × anti-human CD16A recombinant antibody therapy, intravenous infusion intervention 2: NK cell therapy, intravenous infusion intervention 3: Lymphodepleting chemotherapy, intravenous infusion intervention 4: Lymphodepleting chemotherapy, intravenous infusion intervention 5: Immune cytokine, subcutaneously

Protocol documents:
Prot_000.pdf: 
PROTOCOL AFM13-203 
CONFIDENTIAL 
The information contained in this document, especially unpublished data, is confidential communication from 
Affimed GmbH. Acceptance of this document constitutes the agreement of the recipient that this information will 
not be disclosed to others without written authorization from Affimed GmbH, except to the extent necessary for 
Ethics Committee/Institutional Review Board procedures and to obtain written informed consent from those persons 
to whom test drug may be administered.
Protocol 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 CD30-Positive Peripheral T-Cell Lymphoma 
(LuminICE-203) 
Protocol No: 
AFM13-203 
Study Treatments: 
AFM13 (anti-human CD30 × anti-human CD16A recombinant 
antibody) or acimtamig 
AB-101 (Allogeneic Cord Blood Derived NK Cells) or AlloNK® 
Indication(s) Studied: 
Recurrent or Refractory Hodgkin Lymphoma and CD30-Positive 
Peripheral T-Cell Lymphoma 
Study Phase: 
Phase 2 
IND Number: 
029407 
Sponsor Name: 
Affimed GmbH 
Sponsor Address 
Gottlieb-Daimler-Strasse 2,  
68165 Mannheim, Germany 
Version No., Date 
Version 3.0, 03 July 2024 


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SPONSOR SIGNATORY 
This study will be conducted in compliance with International Council for Harmonization (ICH) 
guidelines on Good Clinical Practice (GCP), the Declaration of Helsinki (with amendments), and 
in accordance with local legal and regulatory requirements, including data privacy laws. 
This protocol, V3.0 dated 03 July 2024, has been approved by Affimed GmbH. 
 
 
 
 
Signature: ………………………………… 
Date: ………………… 
 
  
 
 
 
(DD MMM YYYY) 
 
 
Affimed GmbH 
Gottlieb-Daimler-Strasse 2  
68165 Mannheim  
Germany 
 
 
 
  
 
 
 


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COORDINATING INVESTIGATOR 
I declare that the protocol contains all the necessary information required for the conduct of the 
study. 
 
 
 
 
Coordinating Investigator´s Signature 
 Date  
 
 
 


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INVESTIGATOR’S DECLARATION AND APPROVAL 
I have read this protocol and agree that it contains all the necessary details for carrying out this 
study. I will conduct the study as described in the current, approved protocol. I verify that I am 
suitably qualified by education, scientific and medical training and experience to conduct the 
study. Documentation of my qualifications and professional affiliations are contained in my up-
to- date curriculum vitae provided to the Sponsor. 
I will provide the supplied copies of the protocol, including future protocol amendments, and all 
information relating to non-clinical and clinical experience when available (eg, in updated editions 
of the Investigator’s Brochure), to all staff involved in the conduct of this study. I will discuss this 
material with them to ensure that they are fully conversant with the investigational medicinal 
product and study design, and that they will handle the data and information generated in the study 
confidentially. 
I will conduct the study in accordance with Good Clinical Practice, the Declaration of Helsinki, 
and the moral, ethical and scientific principles that justify medical research. I acknowledge that 
the study will be conducted in accordance with the relevant laws and regulations relating to clinical 
studies and the protection of subjects, including data privacy laws. I confirm it is my duty and the 
duty of my study staff to ensure participating subjects are informed comprehensively about the 
nature of the study and will give their written consent to participate before entry into the study. 
Subjects will be informed that they may withdraw from the study at any time without jeopardizing 
their future care. I will use only the subject informed consent form approved by the Sponsor and 
the Ethics Committee/Institutional Review Board for this study. I will supply the Sponsor with any 
material written prepared by myself or my study staff e.g., summary of study, which is given to 
the Ethics Committee/Institutional Review Board in support of the application. 
Where applicable, the subject information contained in clinic records, reports and manuscripts will 
be transcribed to the study case report forms. I (or my delegates as described in my Study File) 
will attest to the authenticity of the data and accuracy and completeness of the transcription by 
signing the case report forms. I agree to the audit and monitoring procedures to verify study records 
against original records. Should it be requested by government regulatory agencies, I will make 
available additional background data from my records and from the hospital or institution where 
the study was conducted (as permitted by the hospital or institution). 
I understand that the case report forms and other data pertinent to this study are the property of 
Affimed GmbH and are confidential. I agree to only supply Affimed GmbH (or their delegates) 
with subject study data in such a way that the subject cannot be personally identified. 
 
Investigator: …………………………………… ………………………………  
Signature  
 
 
 
 
 
 
Date 
Print Name: 
……………………………………………………………………………… 
Institution Name: ……………………………………………………………………………… 
Institution Address:  ……………………………………………………………………………… 


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TABLE OF CONTENTS 
PROTOCOL AFM13-203 ...............................................................................................................1 
SPONSOR SIGNATORY ...............................................................................................................2 
COORDINATING INVESTIGATOR.............................................................................................3 
INVESTIGATOR’S DECLARATION AND APPROVAL ...........................................................4 
TABLE OF CONTENTS .................................................................................................................5 
LIST OF ABBREVIATIONS ........................................................................................................12 
1. 
STUDY SYNOPSIS ...................................................................................................17 
2. 
INTRODUCTION ......................................................................................................29 
2.1. 
Disease Background ...................................................................................................29 
2.2. 
Background of the Study Drugs .................................................................................29 
2.2.1. 
Acimtamig ..................................................................................................................29 
2.2.2. 
AlloNK® .....................................................................................................................30 
2.3. 
Rationale and Benefit-Risk Conclusion ......................................................................31 
2.3.1. 
Overall Rationale for the Study ..................................................................................31 
 
 
 
 
 
 
 
2.3.2.3. 
Lymphodepletion ........................................................................................................36 
2.3.2.4. 
Interleukin-2 (IL-2) .....................................................................................................36 
 
 
2.3.4. 
Benefit-Risk Analysis .................................................................................................38 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................41 
 
 
4. 
OVERALL STUDY DESIGN ....................................................................................43 
 
 
4.1.1. 
Screening Period .........................................................................................................45 
4.1.2. 
Treatment Period ........................................................................................................45 
4.1.3. 
End of Treatment Visit ...............................................................................................46 
 
 
4.1.5. 
Long-Term Follow-Up Period ....................................................................................46 
4.2. 
Study Duration ............................................................................................................46 




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7.1.1. 
Acimtamig Investigational Product, Labeling, Storage, and Handling ......................70 
7.1.2. 
AlloNK® Investigational Product, Labeling, Storage, and Handling .........................70 
7.2. 
Accountability .............................................................................................................71 
7.3. 
Treatment Compliance ................................................................................................72 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................73 
8.1. 
Confirmation of CD30-positive PTCL .......................................................................73 
8.2. 
PTCL Tumor Procurement .........................................................................................73 
8.3. 
Efficacy Assessments .................................................................................................73 
8.4. 
Safety and Tolerability Assessments ..........................................................................74 
8.4.1. 
Medical History ..........................................................................................................74 
8.4.2. 
Pregnancy and Follicle Stimulating Hormone Tests ..................................................74 
8.4.3. 
Eastern Cooperative Oncology Group Performance Status ........................................74 
8.4.4. 
Vital Signs ..................................................................................................................75 
8.4.5. 
Physical Examinations ................................................................................................75 
8.4.6. 
Clinical Chemistry, Hematology, Coagulation, and Urinalysis .................................75 
8.4.7. 
Electrocardiogram .......................................................................................................75 
8.5. 
Pharmacokinetic Sampling .........................................................................................76 
8.6. 
Additional Assessments ..............................................................................................76 
 
 
8.6.2. 
Anti-drug Antibodies ..................................................................................................76 
8.6.3. 
Quality of Life Assessment ........................................................................................76 
8.7. 
Volume of Blood Sampling ........................................................................................77 
9. 
STATISTICAL METHODS AND DATA ANALYSIS ............................................78 
9.1. 
Analysis Sets ...............................................................................................................78 
9.2. 
Sample Size Determination ........................................................................................79 
9.3. 
Randomization ............................................................................................................80 
9.4. 
Demographic, Medical History, Prior Medication and Other Baseline 
Characteristics .............................................................................................................80 
9.5. 
Study Drug ..................................................................................................................80 
9.6. 
Concomitant Medication ............................................................................................80 
 
 
9.7.1. 
ORR by IRC for Cohort 6 ...........................................................................................81 
9.8. 
Secondary Analyses ....................................................................................................81 


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9.8.1. 
Secondary Efficacy Analyses .....................................................................................81 
9.8.1.1. 
Duration of Response by IRC and Investigator ..........................................................81 
9.8.1.2. 
CRR by IRC and Investigator .....................................................................................82 
9.8.1.3. 
ORR by Investigator ...................................................................................................82 
9.8.1.4. 
Progression-free Survival by IRC and Overall Survival ............................................82 
9.8.1.5. 
Subsequent Transplant ................................................................................................82 
9.8.2. 
Safety Analyses ..........................................................................................................82 
9.8.3. 
Immunogenicity Analyses ..........................................................................................82 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10. 
SAFETY MANAGEMENT .......................................................................................85 
10.1. 
Safety Definitions .......................................................................................................85 
10.1.1. 
Adverse Event .............................................................................................................85 
10.1.2. 
Special Considerations Related to AE Reporting .......................................................85 
10.1.3. 
Adverse Events of Special Interest .............................................................................86 
10.1.4. 
Serious Adverse Event ................................................................................................86 
10.1.5. 
Overdose, Medication Error, and Misuse ...................................................................87 
10.2. 
Evaluation and Classification .....................................................................................87 
10.2.1. 
Severity Assessment ...................................................................................................88 
10.2.2. 
Expectedness Assessment ...........................................................................................88 
10.2.3. 
Causality Assessment .................................................................................................89 
10.3. 
Safety Reporting .........................................................................................................90 
10.3.1. 
Safety Reporting of Serious Adverse Events and Adverse Events of Special 
Interest ........................................................................................................................90 
10.3.2. 
Exposure During Pregnancy or Lactation ...................................................................91 
10.3.3. 
Other Reporting Obligations .......................................................................................91 
10.4. 
Follow-Up Information on Reported Events ..............................................................91 


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10.5. 
Reporting of Serious Adverse Events to Regulatory Authorities ...............................92 
10.6. 
Study Interruption or Stopping Criteria for Safety Concerns .....................................92 
11. 
QUALITY, CONTROL, AND QUALITY ASSURANCE .......................................94 
11.1. 
Data Recording, Monitoring of the Study, and Regulatory Compliance ...................94 
11.2. 
Study Monitoring ........................................................................................................94 
11.3. 
Clinical Study Audit ...................................................................................................95 
11.4. 
Clinical Study Report .................................................................................................95 
11.5. 
Data Availability .........................................................................................................95 
11.6. 
Curricula Vitae and Financial Disclosure of Investigators .........................................95 
11.7. 
Protocol Modifications ...............................................................................................95 
11.8. 
Study or Site Termination ...........................................................................................95 
12. 
ETHICAL CONSIDERATIONS ................................................................................97 
12.1. 
Ethical Conduct of the Study ......................................................................................97 
12.2. 
Informed Consent .......................................................................................................97 
12.3. 
Subject Participation Card ..........................................................................................98 
12.4. 
Insurance .....................................................................................................................98 
12.5. 
Institutional Review Board/Independent Ethics Committee ......................................98 
12.6. 
Subject Privacy ...........................................................................................................98 
13. 
DATA HANDLING AND RECORDKEEPING .....................................................100 
13.1. 
Recording of Data .....................................................................................................100 
13.2. 
Study Record Retention ............................................................................................100 
14. 
REFERENCES .........................................................................................................101 
 
 
 
 
 ...............................................
 
 
 
 
 
APPENDIX E. CONTRACEPTIVE GUIDANCE...................................................................121 
Section E.1.  Female Participants .............................................................................................121 
Section E.2.  Male Participants .................................................................................................121 
Section E.3.  Collection of Pregnancy Information ..................................................................121 
 
 
 
 


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APPENDIX H. CAIRO-BISHOP DEFINITION AND GRADING OF TUMOR 
LYSIS SYNDROME ................................................................................................128 
 
 


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LIST OF TABLES 
Table 1: 
Summary of Nonclinical Data: Acimtamig in Combination with AlloNK® ..............38 
Table 2: 
Study Objectives and Endpoints .................................................................................41 
Table 3: 
Grading System for IRR and related Events ...............................................................60 
Table 4: 
Grading System for CRS and Neurotoxicity (ASTCT Grading and ASTCT 
ICANS Grading) .........................................................................................................61 
Table 5: 
Clinical Grading of Acute GVHD (MAGIC Criteria) ................................................63 
 
 
 
 
 
Table 8: 
Relationship to Study Drug ........................................................................................89 
 
 
 
 
 
 
 
 
 
 
 
 
Table 14: Cairo-Bishop Definition of Laboratory Tumor Lysis Syndrome .............................128 
Table 15: Cairo-Bishop Definition of Clinical Tumor Lysis Syndrome ..................................128 
Table 16: Cairo-Bishop Grading Classification of Tumor Lysis Syndrome ............................129 
 
LIST OF FIGURES 
 
 
Figure 2: 
Overall Study Design ..................................................................................................43 
 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition/Explanation 
ADA 
anti-drug antibody 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
ADCP 
antibody-dependent cell-mediated phagocytosis 
AE 
adverse event 
AESI 
adverse event of special interest 
AITL 
angioimmunoblastic T-cell lymphoma 
ALC 
absolute lymphocyte count 
ALCL 
anaplastic large-cell lymphoma 
ALK 
anaplastic lymphoma kinase 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
ASCT 
autologous stem cell transplantation 
AST 
aspartate aminotransferase 
ASTCT 
American Society for Transplantation and Cellular Therapy 
ATC 
Anatomical, Therapeutic, and Chemical 
AUC0-7days 
area under the concentration-time curve from 0 to 7 days. 
AUC0-∞ 
area under the concentration-time curve to infinite time 
BV 
brentuximab vedotin 
CAR-T 
chimeric antigen receptor T-cell 
CBNK 
cord blood natural killer 
CFR 
US Code of Federal Regulations 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CLL 
chronic lymphocytic leukemia  
Cmin 
minimum observed plasma concentration 
CMR 
complete metabolic response 
CMV 
cytomegalovirus 
CNS 
central nervous system 
CR 
complete response/remission 


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Abbreviation 
Definition/Explanation 
CRA 
clinical research associate 
CrCl 
creatinine clearance 
CRP 
C-reactive protein 
CRR 
complete response rate 
CRS 
cytokine release syndrome  
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
Cy/Flu 
cyclophosphamide and fludarabine 
DCR 
disease control rate 
DILI 
drug-induced liver injury 
DL 
dose level 
DLCO 
diffusing capacity of the lungs for carbon monoxide 
DLT 
dose-limiting toxicity 
DOR 
duration of response 
DSUR 
Development Safety Update Report 
EBV 
Epstein Barr Virus 
EC 
Ethics Committee 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
Electronic Data Capture System 
EMA 
Europeans Medicines Agency 
EOI 
end of infusion 
EORTC 
European Organisation for Research and Treatment of Cancer 
EOT 
end of treatment 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
FEV1 
forced expiratory volume 
FSH 
Follicle -stimulating hormone 
FVC 
forced vital capacity 
G-CSF 
granulocyte-colony stimulating factor 
GCP 
Good Clinical Practice 


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Abbreviation 
Definition/Explanation 
GVHD 
graft versus host disease 
Hb 
hemoglobin 
HCT 
hematopoietic cell transplantation 
HIV 
human immunodeficiency virus 
HL  
Hodgkin lymphoma 
HNSTD 
highest non-severely toxic dose 
IA 
interim analysis 
IB 
Investigator’s Brochure 
ICANS 
immune effector cell-associated neurotoxicity syndrome 
ICF 
informed consent form 
ICH 
International Council on Harmonisation 
ID 
identification  
IFN 
interferon 
IHC 
immunohistochemistry 
IL 
interleukin 
IL-2 
interleukin-2 
IME 
important medical event 
IMP 
investigational medicinal product 
IND 
Investigational New Drug Application 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IRC 
Independent Radiology Committee 
IRR 
infusion-related reaction(s) 
ITT 
intent-to-treat 
i.v. 
intravenous(ly) 
LPI 
last patient in 
mAB 
monoclonal antibody 
MAGIC 
Mount Sinai Acute GVHD International Consortium 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRD 
measurable residual disease 
MTD 
maximum tolerated dose 
NCI 
National Cancer Institute  


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Abbreviation 
Definition/Explanation 
NHL 
non-Hodgkin lymphoma 
NK 
Natural killer 
NOS 
not otherwise specified 
NYHA 
New York Heart Association 
ORR 
objective response rate 
OS 
overall survival 
PBMC 
peripheral blood mononuclear cells 
PCR 
polymerase chain reaction 
PD 
pharmacodynamic(s)  
PD-1 
receptor for programmed death-ligand 1 
PET-CT 
positron emission tomography-computed tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PMD 
progressive metabolic disease 
PMR 
partial metabolic response 
popPK 
population PK  
PPS 
per protocol set 
PR 
partial response 
PRES 
posterior reversible encephalopathy syndrome 
PRO 
patient-reported outcome measures 
PRR 
Partial Responses Rate 
PS 
performance status 
PTCL 
peripheral T-cell lymphoma  
PTCL-NOS 
peripheral T-cell lymphoma not otherwise specified  
QoL  
quality of life 
QTcF 
QT interval with Fridericia’s correction 
QW 
once weekly 
R/R 
refractory/relapsed  
RO  
receptor occupancy  
RP2D 
recommended Phase 2 dose 
RSI 
Reference Safety Information 
SAE 
serious adverse event 


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Abbreviation 
Definition/Explanation 
SAP 
Statistical Analysis Plan 
SAS 
safety analysis set 
SCT 
stem cell transplantation 
SD 
stable disease 
SRC 
Safety Review Committee 
SRI 
safety run-in set 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
TLS 
tumor lysis syndrome 
TMF 
Trial Master File 
Treg 
Regulatory T cells 
ULN 
upper limit of normal 
USPI 
United States Prescribing Information 
VH/VL 
heavy chain/light chain 
WHO 
World Health Organization 
 






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Overall Study Design  
 
Abbreviations: CD = cluster differentiation; cHL = classical Hodgkin lymphoma; Cy/Flu = cyclophosphamide and fludarabine; 
IA = interim analysis; IL = interleukin; NK = natural killer; PTCL = peripheral T-cell lymphoma; DL1 = 2 × 109 cells on Day 1, 
Day 8, and Day 15; DL2 = 4 × 109 cells at Day 1, 2 × 109 cells at Day 8 and Day 15 
 
 
 
 
 
 
 
A safety run-in for the first 6 classical HL subjects in Cohort 1 and Cohort 2 (parallel enrollment) will be 
implemented, with staggering of at least 12 days between Day -5 (start of lymphodepletion) of one subject 
to Day -5 (start of lymphodepletion) of the subsequent subject (included as part of the 12-day period is a 
7-day observation period following administration of Day 1 treatment). For the first 3 subjects enrolled in 
each cohort, the safety run-in approach will be utilized to monitor treatment-related toxicities during the 
safety run-in observation period, defined as the time from the first dose of combination study treatment 
(acimtamig/AlloNK®) to Day 21 of the treatment cycle (C1D21) for each subject. If a Grade 3 or Grade 4 
acimtamig or AlloNK®-related TEAE (meeting criteria as stipulated in Section 10.6) occurs during the 
safety run-in observation period for the first 3 subjects, then another 3 subjects will be enrolled using the 
same staggered approach. If no more than one Grade 3 or 4 acimtamig or AlloNK®-related TEAE is 
observed in the first 6 subjects, then enrollment of the first 3 classical HL subjects in Cohort 3 and Cohort 
4 (parallel enrollment) will begin, using the same staggering approach outlined for Cohort 1 and Cohort 2. 
If Grade 3 or 4 acimtamig or AlloNK®-related TEAEs are not observed in the first 3 subjects, then 
enrollment in Cohort 1 and Cohort 2 may continue without staggering and enrollment of the first 3 classical 
HL subjects in Cohorts 3 and 4 (parallel enrollment) will begin, using the same staggering approach as 
outlined for Cohort 1 and Cohort 2. Backfilling into Cohorts 1 and 2 will be allowed during the safety 
clearance period for Cohorts 3 and 4. 




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collected and analyzed at specified times for measurement of acimtamig and AlloNK®. The PK of 
acimtamig and AlloNK® will be determined by analyzing samples collected at the time points as indicated 
in the Schedule of Pharmacokinetic, Pharmacodynamic, Immunogenicity, and Translational Assessments 
(
).  
Pharmacodynamic Assessments 
Pharmacodynamic markers evaluation, e.g., immunophenotyping, cytokines, etc., will be collected from all 
subjects on study to further explore acimtamig and AlloNK® activity and identify potential predictors of 
response. Pharmacodynamic sampling is performed as indicated in the Schedule of Pharmacokinetic, 
Pharmacodynamic, Immunogenicity, and Translational Assessments (
). 
The Sponsor may conduct additional analyses on the PD samples to further evaluate the safety of the study 
treatment, to better understand the progression of the disease, or to assess response to the study treatment. 
Immunogenicity 
The development of ADA may impact drug exposure, efficacy and safety in subjects on the study. To assess 
the immunogenicity of acimtamig and AlloNK®, ADAs will be measured as indicated in the Schedule of 
Pharmacokinetic, Pharmacodynamic, Immunogenicity, and Translational Assessments (
 
. 
Patient Reported Outcomes (PROs) 
PROs on QoL will be measured utilizing European Organisation for Research and Treatment of Cancer 
(EORTC) QLQ-C30. 
Criteria for Study Inclusion 
Subjects will be considered eligible to be enrolled in the study if ALL of the inclusion and NONE of the 
exclusion criteria are met as defined below. Prospective approval of protocol deviations to recruitment and 
enrollment criteria, also known as protocol waivers or exemptions, is not permitted.  
Inclusion Criteria 
A subject is eligible to be included in the study only if ALL the following criteria apply: 
1. Subjects with a diagnosis of FDG-avid relapsed or refractory classical HL OR select subtypes of 
FDG-avid 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 (Note: Archival tissue may be 
substituted for a fresh tumor biopsy, please refer to Section 8.1 and the Schedule of Assessments  
[
] for additional details).  
PTCL subtypes 
• 
Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) 
• 
Angioimmunoblastic T-cell lymphoma 
• 
Anaplastic large-cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-
positive 
• 
ALCL, ALK-negative 
2. Prior treatment for the disease under study consistent with the following: 
• 
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 


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have included brentuximab vedotin and a receptor for programmed death-ligand 1 
(PD-1) 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 autologous stem cell 
transplant (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 chimeric antigen receptor T-cell (CAR-T) therapy is permitted if 
last CAR-T dose completed at least 6 months prior to the first dose of study drug 
(acimtamig and/or AlloNK®). 
3. Male or female aged ≥18 years (or as required by local regulation) on the day of signing the 
informed consent form (ICF). 
4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1. 
5. Absolute neutrophil count (ANC) ≥1000/mm3, hemoglobin ≥7 g/dL, and platelet count 
≥50,000/mm3. 
• 
Transfusions of packed red blood cells and platelets are allowed up to 2 weeks prior 
to Day -5 of the first cycle and as needed during the Treatment Period. Growth 
factors are allowed during Screening up to 2 weeks prior to the first dose of 
lymphodepleting chemotherapy and as needed during the Treatment Period. All lab 
parameters should be checked within 2 days of the first dose of lymphodepleting 
chemotherapy to reassess eligibility. 
6. Adequate organ function defined by the following laboratory parameters during screening: 
• 
Direct (conjugated) bilirubin ≤ 2 × the upper limit of normal (ULN), or total 
bilirubin ≤ 3 × ULN if considered due to Gilbert’s disease.  
• 
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × 
ULN, unless considered due to malignant disease involvement, in which case AST 
and ALT can be ≤ 5.0 × ULN. 
• 
Creatinine clearance (CrCl) ≥50 mL/min. Creatinine clearance will be calculated 
using the Cockcroft and Gault equation. 
• 
International normalized ratio (INR) <1.5 × ULN and activated partial 
thromboplastin time (aPTT) <1.5 × ULN (for subjects not receiving therapeutic 
anticoagulation) (Note: subjects receiving therapeutic anticoagulation may enroll 
with INR ≥1.5 × ULN).  
7. Adequate pulmonary function with forced expiratory volume (FEV1), forced vital capacity (FVC) 
and diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for Hgb and volume) 
≥50%. 
8. Adequate cardiac function with left ventricular ejection fraction ≥50% and no uncontrolled 
arrhythmias or symptomatic cardiac disease. 
9. Capable of giving signed informed consent that includes compliance with the requirements and 
restrictions listed in the ICF and in the study protocol. 


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10. Female subjects must have a negative urine or serum pregnancy test within 7 days prior to first dose 
of lymphodepletion if of childbearing potential or be of non-childbearing potential. If the urine 
pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be 
required. The serum pregnancy test must be negative for the subject to be eligible. Non-childbearing 
potential is defined as: 
• 
Postmenopausal, defined as no menses for 12 months without an alternative 
medical cause. A high follicle-stimulating hormone (FSH) level in the 
postmenopausal range may be used to confirm a post-menopausal state in women 
not using hormonal contraception or hormonal replacement therapy. However, in 
the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.  
• 
Surgically sterile. Surgical sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy. 
11. Females of childbearing potential must agree to sexual abstinence (defined below) or be willing to 
use a highly effective method of contraception for the course of the study from 14 days prior to the 
first dose of lymphodepletion through 120 days after the last dose of study drug (acimtamig and/or 
AlloNK®). Acceptable highly effective birth control methods include: 
• 
Oral, intravaginal, or transdermal combined (estrogen and progestogen containing) 
hormonal contraception associated with inhibition of ovulation;  
• 
Oral, injectable, or implantable progestogen-only hormonal contraception 
associated with inhibition of ovulation;  
• 
Intrauterine device;  
• 
Intrauterine hormone-releasing system;  
• 
Bilateral tubal occlusion;  
• 
Vasectomized partner (provided that partner is the sole sexual partner of the female 
of reproductive potential and that the vasectomized partner has received medical 
assessment of the surgical success); and  
• 
Sexual abstinence. 
In the context of this study, sexual abstinence is considered a highly effective 
method only if defined as refraining from heterosexual intercourse from 14 days 
prior to the first dose of lymphodepletion up to 120 days after the last dose of study 
drug (acimtamig or AlloNK®). The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the clinical study and the preferred and usual 
lifestyle of the subject. 
12. Males who have female partners of childbearing potential must agree to use a highly effective 
method of contraception as described in inclusion criterion 11, starting with the first dose of 
lymphodepletion through 120 days after the last dose of study drug (acimtamig and/or AlloNK®). 
Exclusion Criteria 
A subject is not eligible to enroll into the study if they have ANY of the following: 
1. Treatment within prior 3 weeks of Day 1 of treatment schedule (Cycle 1 Day 1) with any anti-
cancer agent, investigational or approved. 
2. Continued toxicity from prior treatment that has not resolved to Grade ≤ 1, with allowable 
exceptions (e.g., alopecia). 


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3. Active central nervous system (CNS) involvement (untreated or uncontrolled parenchymal brain 
metastasis or positive cytology of cerebrospinal fluid). 
4. Previous treatment with acimtamig or cord blood derived NK (CBNK) cells. 
5. Known hypersensitivity/allergic reaction ≥Grade 3 to monoclonal antibodies (mAb) or any 
components used in the acimtamig product preparation, any history of anaphylaxis or uncontrolled 
asthma.  
6. History of a solid organ allograft, or an inflammatory or autoimmune disease likely to be 
exacerbated by IL-2 or other study specific treatment (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. Exceptions include any subject 
on 10 mg or less of prednisone or equivalent, subjects with vitiligo, hypothyroidism stable on 
hormone replacement, Type I diabetes, Graves’ disease, Hashimoto’s disease, alopecia areata, 
eczema, or psoriasis). 
7. Treatment with any therapeutic mAb or immunosuppressive medications (such as high-dose 
steroids defined as ≥10 mg prednisone or equivalent per day) within 4 weeks or 5 half-lives 
(whichever is shorter) of Day 1 of treatment schedule. 
Exceptions for the use of corticosteroids: 
• 
Topical (≤20% of the skin surface area), ocular, intra-articular, intranasal, or 
inhalation corticosteroids with minimal systemic absorption. 
• 
Short course (≤7 days) of corticosteroids prescribed prophylactically (e.g., for 
contrast dye allergy or antiemetic therapy for specific chemotherapy) or for 
treatment of a non-autoimmune causes (e.g., delayed-type hypersensitivity reaction 
caused by contact allergen) as long as <10 mg prednisone equivalent. 
• 
Physiologic corticosteroid replacement therapy for adrenal or pituitary 
insufficiency. 
8. History of any other systemic malignancy, unless previously treated with curative intent and the 
subject has been disease free for 2 years or longer. Subjects who meet the above criteria and are on 
maintenance therapy for prior malignancy may be eligible after discussion and approval from the 
medical monitor. 
9. Live-virus vaccines given within 28 days prior to the initiation of study treatment. 
10. Active, uncontrolled infection requiring systemic therapy. If the infection is controlled or has 
resolved, maintenance and/or prophylactic systemic antimicrobials are permitted. 
11. Known active hepatitis B or hepatitis C as defined in the table below. Antiviral prophylaxis for 
chronic hepatitis B virus infection may be used at the discretion of the Investigator.  
Note: Subjects meeting following criteria are allowed to be enrolled in the study: 
 
Eligible 
HBV 
HB sAg (-) 
HB sAg (+) and HBV DNA <500 IU/mL (or 2500 copies/mL) 
HCV 
HCV Ab (-) 
HCV Ab (+) and HCV RNA (-) 
Abbreviations: HBV = hepatitis B virus; HBs Ag = HBV surface antigen; HCV = hepatitis C virus; 
HCV Ab = HCV antibody  
12. Active HIV infection as evidenced by a positive HIV polymerase chain reaction (PCR) test result. 
13. Active acute or chronic GVHD or GVHD requiring immunosuppressive treatment, clinically 
significant CNS dysfunction (seizure disorder, dementia, cerebellar disease, cerebral edema, 


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posterior reversible encephalopathy syndrome (PRES), autoimmune disease with CNS 
involvement).  
14. Any uncontrolled medical condition, including but not limited to: unstable angina pectoris, 
symptomatic congestive heart failure (New York Heart Association [NYHA] II, III, IV;, myocardial 
infarction ≤6 months prior to first study drug (acimtamig or AlloNK®), uncontrolled cardiac 
arrhythmia e.g., atrial fibrillation/flutter, cerebrovascular accidents ≤6 months before first dose of 
study drug (acimtamig and/or AlloNK®).  
15. Major surgical procedure (i.e., any open surgical procedure that involves the resection or 
manipulation of major organ) or significant traumatic injury within 4 weeks before first dose of 
study drug (acimtamig and/or AlloNK®) or anticipation of need of a major surgical procedure 
during the course of study. 
Note: Procedures that are considered to be minimally invasive (e.g., peripherally inserted central 
catheters lines and/or port placements, interventional biopsies) will be exceptions. 
16. Pregnant or breastfeeding women. Breastfeeding must be discontinued before onset of and during 
treatment and should be discontinued for at least 3 months after end of treatment. 
17. Substance abuse, medical, psychological, or social conditions that may interfere with the subject’s 
cooperation with the requirements of the study or evaluation of the study results. 
18. Any medical, psychological, or social condition that would interfere with the subject’s participation 
in the study. 
Study Treatment, Dose, and Mode of Administration 
Study treatments will be administered as follows in 48-day cycles, up to 3 cycles in total, with a 2-week (+2 
week) rest period between each cycle (refer also to Figure 2): 
• 
Lymphodepletion: A standard lymphodepleting regimen of cyclophosphamide 300 mg/m2/day and 
fludarabine 30mg/m2/day intravenously will be administered from Day -5 to Day -3 at the start of 
each treatment cycle (Section 6.1.1). 
▪ 
Premedication: Approximately 1 hour prior to acimtamig administration and approximately 
30 min prior to AlloNK® administration, a premedication regimen will be administered as 
follows 
 
o Intravenous (IV) H1 antagonist (e.g., diphenhydramine 50 mg or similar medication as used 
per local institutional practice) with or without an H2 antagonist (e.g., famotidine or similar 
medication as used per local institutional practice), and 
o Oral acetaminophen dosage as per local institutional practice (e.g., 650 mg to 1000 mg or 
equivalent). 
• 
Acimtamig: Acimtamig will be administered intravenously at a fixed dose of 200 mg or 300 mg 
on Day 1, Day 8, and Day 15 of each cycle prior to administration of AlloNK® on these days. 
Infusions will be administered over approximately 4 hours. Additionally, acimtamig will be 
administered as the sole therapy (intravenously over approximately 4 hours) on Day 22, Day 29 
and Day 36 of each cycle (Section 6.1.3). 
• 
AlloNK®: AlloNK® will be administered (as soon as practical after thawing but must be within 90 
minutes after thawing) upon completion of administration and observation period for acimtamig. 
Subjects at DL1 will be administered a fixed dose of 2 × 109 cells IV on Day 1, Day 8 and Day 15 
of each cycle. Subjects at DL2 will be administered a fixed dose of 4 × 109 cells IV on Day 1 and a 


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dose of 2 × 109 cells IV on Day 8 and Day 15 in an identical manner and schedule as DL1. 
(Section 6.1.4).  
• 
IL-2: IL-2 will be administered at a dose of 6 × 106 IU/dose subcutaneously at least 1 hour after 
and no more than 4 hours following each AlloNK® dose for all subjects who were initially consented 
under protocol v2.0 (Section 6.1.5). Those subjects initially consented under protocol v3.0 and later 
versions will not receive IL-2 following the AlloNK® treatment.  
After administration of each acimtamig, AlloNK® and IL-2 (if applicable per consented protocol version) 
in the treatment regimen, subjects must be observed for at least 1 hour.  
Statistical Considerations 
Analyses Sets 
The safety analysis set (SAS) will consist of all subjects who received any amount of any component of 
the regimen (acimtamig, AlloNK® or any study treatment such as lymphodepletion or IL-2). The SAS will 
be the primary population for all safety-related endpoints.  
Following the intent-to-treat (ITT) principle, the full analysis set (FAS) will consist of all subjects enrolled 
into one of the two selected cHL Cohorts in Stage 1 and Stage 2 or the exploratory PTCL Cohort (Cohort 
5), who received at least 1 dose of both acimtamig and AlloNK®. The FAS will be the primary population 
for all efficacy related endpoints. 
Following the ITT principle for analysis of Cohort 6, the NK full analysis set (NK-FAS) will consist of all 
subjects who received at least 1 dose of AlloNK® in Cohort 6. The NK-FAS will be the primary population 
for all efficacy related endpoints concerning Cohort 6. 
The per protocol set (PPS) will consist of all subjects in FAS who did not have any major protocol 
deviations. The primary analysis will be repeated to support the results of the primary analysis on the FAS. 
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 acimtamig and AlloNK® combination dose during Cycle 1. 
The acimtamig PK set consists of all subjects (except those from Cohort 6) who have received at least 1 
dose of acimtamig and have at least 1 post dose acimtamig PK measurement. 
The AlloNK® PK set consists of all subjects who have received at least 1 dose of AlloNK® and have at 
least 1 post dose AlloNK® PK measurement. 
 
 
 
 
 
 
 
 
 
 
 
 


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Secondary Analyses 
Efficacy 
The following secondary efficacy endpoints will be assessed according to the Lugano classification (Cheson 
2014; 
 
• 
DOR by IRC and Investigator 
• 
ORR (CR + PR) by Investigator 
• 
CRR by IRC and Investigator 
• 
PFS by IRC 
In addition, incidence of subjects receiving subsequent transplant and OS will be assessed. 
Safety 
Incidence, severity and relatedness of TEAEs and SAEs. Adverse events will be coded with Medical 
Dictionary for Regulatory Activities (MedDRA) for regulatory standardization and graded according to the 
NCI CTCAE v5.0 (including neurotoxicities that are not considered ICANS) except for CRS and ICANS 
which will be graded according to the ASTCT grading, TLS will be graded according to the Cairo-Bishop 
TLS grading system and acute GVHD will be graded according to the MAGIC criteria. 
Immunogenicity 
Immunogenicity parameters will be summarized by descriptive statistics. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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2. 
INTRODUCTION 
This clinical study will evaluate acimtamig in combination with AlloNK® in subjects with 
recurrent or refractory Hodgkin lymphoma and CD30-positive peripheral T-cell lymphoma 
(PTCL). 
2.1. 
Disease Background 
CD30 is a cell membrane protein of the tumor necrosis factor receptor family universally expressed 
in classical Hodgkin lymphoma (HL) as well as in several sub-types of PTCLs, to varying degrees, 
including anaplastic large-cell lymphoma (ALCL), peripheral T-cell lymphoma, not otherwise 
specified (PTCL-NOS), and angioimmunoblastic T-cell lymphoma (AITL).  
In classical HL, the most common CD30-positive lymphoma, frontline chemotherapy (ABVD or 
BEACOPP) with or without radiotherapy has demonstrated significant effectiveness. In patients 
with advanced classical HL, frontline therapy may also include the CD30-targeting antibody drug 
conjugate brentuximab vedotin with chemotherapy (AVD). However, up to 30% of patients are 
refractory to frontline treatment or will relapse. For patients with relapsed or refractory classical 
HL, 50% or fewer can be cured with high-dose chemotherapy and autologous stem cell 
transplantation (ASCT) (Majhail 2006; Josting 2010; Bartlett 2020). Relapse after ASCT is 
associated with a poor prognosis with a median survival of 26 months (Voorhees 2020). Systemic 
treatment options for refractory/relapsed (R/R) patients may also include agents such as 
brentuximab vedotin either as monotherapy or in combination with another agent, and/or a 
PD-(L)1 inhibitor. Despite recent advancements that have included promising targeted and 
immunological agents, there is still an unmet medical need for treatments in the R/R setting that 
provide a high level of response, longer duration of response, and chance of cure, together with a 
clinically acceptable safety profile. 
With respect to PTCLs, first-line treatment with CHOP or CHOP-like regimens results in poor 
outcomes, except in the case of ALK+ ALCL. Despite intensified approaches in frontline therapy, 
such as consolidation with ASCT, these patients are still at considerable risk of relapse or early 
progression. In general, most if not all patients undergoing treatment for PTCL will not achieve 
remission or will relapse with very poor long-term survival, especially in absence of hematopoietic 
cell transplantation (HCT), with median progression-free survival (PFS) and overall survival (OS) 
estimates as low as 3 and 6 months, respectively (Mak 2013; Biasoli 2015; Bellei 2018). Therefore, 
novel therapeutics and treatment strategies are needed to address the unmet medical needs that 
exist for patients with PTCL. 
2.2. 
Background of the Study Drugs  
2.2.1. 
Acimtamig  
Acimtamig, or AFM13, is a tetravalent bispecific (anti-human CD30 × anti-human CD16A) 
recombinant antibody construct, which is being investigated for the treatment of HL and other 
CD30-positive malignancies including PTCL. Acimtamig targets CD30 antigen expressed on 
malignant lymphoma cells. At the same time, the anti-CD16A domains bind to CD16A (FcγRIIIA) 
on natural killer (NK) cells and macrophages. Acimtamig forms a bridge between the tumor target 
cells and innate effector cells, triggering lysis of CD30 antigen-positive cells by NK cells via 




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• KIR-B haplotype. KIR-B haplotype has been associated with improved clinical outcomes 
in the haploidentical transplant setting and greater therapeutic potential in the allogeneic 
setting 
• CD16 F158V polymorphism. The higher-affinity CD16 F158V variant binding to mAb Fc-
domain is seen to facilitate enhanced ADCC.  
• Unmodified NK cells. No genetic enhancement or gene editing is required for, or is a part 
of, the AlloNK® drug product. 
AlloNK® has demonstrated direct, specific, and potent killing of multiple tumor cell lines in vitro 
and in vivo when combined with tumor targeting monoclonal antibodies and NK cell engaging bi-
specific antibodies. AlloNK® has also demonstrated the ability to secrete cytokines such as tumor 
necrosis TNFα and IFNγ upon activation. 
Nonclinical and clinical data for AlloNK® are described in the AlloNK® IB. 
2.3. 
Rationale and Benefit-Risk Conclusion 
2.3.1. 
Overall Rationale for the Study 
Natural killer cell populations are absent in the immunosuppressive tumor microenvironment of 
HL. Furthermore, NK cells from patients with HL are dysfunctional, due in part to an imbalance 
in activating and inhibitory receptors (Reiners 2022). Because of these limitations in autologous 
NK cell function, optimal NK immunotherapy for HL likely requires an allogeneic source.  
The combination of acimtamig with AlloNK® may prove to be a promising treatment option with 
the potential to synergistically increase the effect and direct the anti-tumor cytolytic activity of NK 
cells towards HL and CD30-positive PTCL cells. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 












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influence of the cytokine-deprived tumor microenvironment (Katakam 2006). Therefore, the 
presence of IL-2 may help to establish a more favorable microenvironment to maintain in vivo 
survival of NK cells. In fact, several clinical studies have demonstrated that low-dose IL-2 given 
after NK cell infusion can selectively promote NK cell expansion and persistence (Fehniger 2000, 
Szmania 2015) but the contribution of IL-2 to efficacy is not completely established. Repeated 
administrations of IL-2 at the planned dose given in this trial are not associated with severe adverse 
events (e.g., capillary leak syndrome and renal failure in patients) and are not expected to sensitize 
regulatory T cells (Tregs) that could otherwise out-compete NK cells for IL-2 (Gasteiger 2013) 
but have a known risk of gastrointestinal, constitutional, and hematological toxicities (Fleming 
2002). Thus, in this clinical study, all subjects who have initially consented under protocol v2.0 
will receive 6 × 106 IU of IL-2 subcutaneously at least 1 hour but no more than 4 hours after the 
completion of each weekly dose of AlloNK® for a maximum of 3 weekly doses per cycle. Based 
on pharmacokinetic data for AlloNK® in NHL (NCT04673617) removal of IL-2 did not lead to 
meaningful differences in peak level of AlloNK® in peripheral blood. Therefore, all subjects who 
have initially consented under protocol v3.0 and later versions will not receive IL-2 after AlloNK® 
treatment to reduce the burden of potential associated adverse events and dosing complexity.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  


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Table 1: 
Summary of Nonclinical Data: Acimtamig in Combination with AlloNK® 
Type of Study  
 Test system 
Noteworthy Findings  
Study Number  
Assessment of 
acimtamig binding 
to AlloNK® cells 
relative to CD16 
expression  
NK cells; AlloNK® 
cells; acimtamig; in 
vitro 
The pattern of acimtamig binding to AlloNK® 
cells was congruent to the frequency of 
CD16A+ AlloNK® cells, suggesting that 
acimtamig can saturate CD16A expressed on 
AlloNK® cells. This robust homogenous 
binding was observed when acimtamig was 
pre-complexed with AlloNK® cells prior to 
cryopreservation and after cryopreservation.  
 
AFM13-AB-101-
001  
Assessment of 
acimtamig-mediated 
cytotoxic activity by 
AlloNK®  
AlloNK® cells; 
Karpas-299 
cells; acimtamig; in 
vitro 
The combination of acimtamig with AlloNK® 
cells demonstrated enhanced cytotoxic activity 
towards CD30-positive tumor cells. This 
activity was shown both when acimtamig was 
pre-complexed with AlloNK® cells prior to 
cryopreservation and after cryopreservation. 
Furthermore, the acimtamig-induced cytotoxic 
activity of AlloNK® was associated with an 
enhanced functional activation status reflected 
by increased degranulation/CD107a 
expression and IFN-γ production by AlloNK® 
cells in response to Karpas-299 cells  
AFM13-AB-101-
002  
 on 
intravenous (i.v.) 
Karpas-299/Luc 
cells in IL-15 NOG 
mice during 
cotreatment with 
NK cell product 
AlloNK® and 
acimtamig   
IL-15 NOG mice; 
Karpas-299/Luc 
cells; AlloNK® cells; 
acimtamig; in vivo 
The lymphoma cell line Karpas-299/Luc 
model in IL-15 NOG mice was used to assess 
the efficacy of AlloNK® in combination with 
acimtamig. Significant anti-tumor efficacy 
was observed in groups receiving AlloNK® in 
combination with acimtamig compared to 
control groups.   
 
MV17746  
Overall, based on preclinical data generated with combining acimtamig with AlloNK®, as well as 
previous experience of administering acimtamig with a similar CBNK cell product with a positive 
benefit-risk profile (AFM13-104 study), it is anticipated that acimtamig administered in 
combination with AlloNK® has the potential to generate a robust ADCC response and clinical 
activity in subjects with relapsed or refractory HL and CD30-positive PTCL. 
2.3.4. 
Benefit-Risk Analysis 
Hodgkin lymphoma and PTCL are serious diseases with significant unmet medical need, 
particularly in the R/R setting, requiring investigation of novel treatment regimens. 
Acimtamig is a tetravalent bispecific (anti-human CD30 × anti-human CD16A) recombinant 
antibody construct which targets the CD30 antigen expressed on malignant lymphoma cells. In 
addition, the anti-CD16A domains of acimtamig simultaneously bind to CD16A (FcRIIIA), 
independent of CD16A genotype, on NK cells and macrophages, leading to lysis of CD30 antigen-
positive cells by NK cells via ADCC and ADCP. Acimtamig has demonstrated a toxicity profile 
that has been generally safe in both the monotherapy and combination therapy setting, with 


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manageable toxicities including IRRs. To mitigate the risk of developing IRRs due to acimtamig 
infusion and/or AlloNK®, premedication with intravenous (i.v.) H1 with or without H2 antagonist 
and oral acetaminophen will be required prior to the infusion (Section 6.1.2). In addition, all 
subjects who are treated with acimtamig/AlloNK® must be observed for at least 1 hour post-
infusion. Other potential risks for acimtamig are serious and opportunistic infections, for which 
there will be close monitoring with subjects receiving appropriate supportive care as clinically 
indicated.  
AlloNK® is composed of expanded allogeneic NK cells, cryopreserved in an infusion-ready 
suspension medium. NK cells have been proven to target and kill cancer cells in a manner not 
dependent on human leukocyte antigen, and, therefore, may have clinical utility in cancer patients 
(Farag 2002; Moretta 2008; Ruggeri 2002). Based on clinical studies using allogeneic NK cells in 
oncology treatment as well as clinical data to date, AlloNK® is expected to be well tolerated with 
few, if any, drug-related adverse events (AEs) (Kim 2006; Ljunggren 2007; Yang 2016). The 
safety of AlloNK® monotherapy at a dose level of 1 billion cells and 4 billion cells has been shown 
to be generally safe and well tolerated (Study AB-101-01). To date, risks associated with AlloNK® 
have been limited to non-serious and non-severe events of CRS. Other potential risks that will be 
reduced by intensified premedication regimen and monitored throughout the study are risks 
associated with allergic and infusion reactions, infection, immune effector cell-associated 
neurotoxicity syndrome, and tumor lysis syndrome (TLS) (refer to the AlloNK® IB). AlloNK® is 
a commercially scaled and cryopreserved allogeneic NK cell product, derived from cord blood, in 
an infusion-ready media, which in combination with acimtamig may provide robust anti-tumor 
activity in subjects with relapsed or refractory HL and CD30-positive PTCL. 
Benefits of lymphodepletion include the dampening of the endogenous T-cell response and the 
provision of an improved environment for the activity of AlloNK® (Section 2.3.2.3). 
Lymphodepleting chemotherapy (fludarabine and cyclophosphamide) may result in hematologic 
toxicities that are typically transient and include low white and red blood cell as well as platelet 
counts. Low absolute neutrophil counts (ANCs) and absolute lymphocyte counts (ALCs), and the 
extended depression of CD4-lymphocyte counts are also common. Opportunistic infections may 
occur (Dudley 2005). Study subjects will receive prophylaxis for infection with pneumocystis 
pneumonia, herpes virus and fungal infections according to National Comprehensive Cancer 
Network guidelines (NCCN 2022) or standard institutional practice. To lessen these risks, subjects 
will be monitored closely and receive supportive care as needed. 
Potential benefits of IL-2 administration may include the establishment of a more favorable 
microenvironment to maintain in vivo survival of NK cells (Section 2.3.2.4). IL-2 given 
subcutaneously at the dose administered in this study may result in Grade 1 to 2 side effects, 
including injection-site pain as well as gastrointestinal, constitutional, and hematological toxicities 
(Fleming 2002). To lessen these risks and to reduce the dosing complexity, all subjects who are 
initially consented under protocol v3.0 and later will not receive IL-2 administrations. All subjects 
with or without IL-2 treatment will be monitored closely and receive supportive care as needed.   
The safety profile of acimtamig has been well characterized in clinical studies with IRRs as a 
known risk and infections as potential risk. IRRs and infections are potential risks associated with 
NK cell products and cell therapy products in general (refer to the AlloNK® IB, Artiva IND 
024149). IRRs are deemed manageable, based on prior clinical experience with interventions for 
prophylaxis and treatment. Toxicities overall are expected to be manageable, based on the clinical 


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experience with each drug administered as monotherapy and in combination with other anti-cancer 
therapies.  
Although no CRS cases were reported in monotherapy studies, five CRS events occurred in three 
subjects during Study AFM13-203, where acimtamig was combined with AlloNK®, an allogeneic, 
cord blood-derived NK-cell product. Most CRS events were mild to moderate in severity, and only 
one severe (ASTCT Grade 3) CRS event was reported. All events resolved quickly with standard 
care, and none resulted in permanent study drug discontinuation. The subject who experienced the 
Grade 3 event was later re-exposed to acimtamig without any re-occurrence of severe CRS or IRR 
reactions. The risk of CRS is under observation due to limited available data. Nevertheless, 
mitigation strategies (see Section 6.3.4) were optimized in this protocol version for the first and 
subsequent doses of actimtamig and AlloNK® combination to further reduce the risk of immune 
mediated events (i.e. IRRs or CRS). 
In summary, the known clinical safety profile of acimtamig and AlloNK® monotherapy or other 
NK cell products can be considered tolerable and manageable. The combination of both drugs does 
not raise the expectation of potential overlapping toxicities, except for IRR/CRS and infections 
which are considered to be manageable based on available clinical data. This study utilizes a safety 
run-in for the first 6 subjects with R/R classical HL in each of the 4 cohorts testing the planned 
doses of acimtamig and AlloNK®, with staggering of 12 days between Day -5 (start of 
lymphodepletion) of one subject to Day -5 (start of lymphodepletion) of the subsequent subject 
(includes a 7-day observation period following administration of Day 1 treatment as part of the 
12-day period).  
Overall, the combination of acimtamig with AlloNK® may prove to be a promising treatment 
option with the potential to synergistically increase the effect of and direct the anti-tumor cytolytic 
activity of NK cells towards HL and CD30-positive PTCL. The benefit-risk analysis is considered 
acceptable for the investigation of acimtamig in combination with AlloNK® in HL and CD30-
positive PTCL. On 11-Apr-2024, an independent safety committee reviewed the safety and if 
available efficacy data from eight subjects (including the first four subjects of each of the first two 
cohorts) of Study AFM13-203. The committee endorsed the benefit-risk assessment and agreed 
that enrollment in Cohorts 1 and 2 should continue until fully enrolled. Subsequently, enrollment 
in Cohorts 3 and 4 will commence. 


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3. 
OBJECTIVES AND ENDPOINTS 
Table 2: 
Study Objectives and Endpoints 
 
Primary Objective 
Primary Endpoint 
• 
Assess 
the 
antitumor 
activity 
of 
acimtamig in combination with AlloNK® 
in subjects with R/R classical HL and 
CD30-positive PTCLs by ORR. 
• 
ORR (CR + PR) by Independent Radiology Committee 
(IRC) based on positron emission tomography-computed 
tomography (PET-CT) as assessed by the Lugano 
classification 
Secondary Objectives  
Secondary Endpoints 
• 
To assess efficacy of acimtamig in 
combination with AlloNK®  
• 
To assess the incidence of post-treatment 
transplant  
• 
To assess the safety and tolerability of 
acimtamig in combination with AlloNK® 
• 
To 
assess 
the 
immunogenicity 
of 
acimtamig in combination with AlloNK® 
• 
DOR by Investigator and IRC 
• 
Complete response rate (CRR) by Investigator and IRC 
• 
ORR by Investigator based on PET-CT as assessed by the 
Lugano classification 
• 
Incidence of subjects receiving subsequent transplant  
• 
Frequency of subjects with study-drug related TEAEs and 
SAEs (evaluated using NCI CTCAE v5.0 and ASTCT 
grading for TEAES related to CRS and ICANS) 
• 
Frequency of subjects developing ADAs against acimtamig 
or AlloNK® 
• 
PFS by IRC  
• 
OS 
Exploratory Objectives 
Exploratory Assessments 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  


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4. 
OVERALL STUDY DESIGN 
This 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 acimtamig in combination 
with AlloNK® in subjects with R/R classical HL and CD30-positive PTCL. 
A schematic of the study design is provided in Figure 2. Refer to the Schedule of Assessments 
) for details of procedures and assessments to be performed. 
Figure 2: 
Overall Study Design 
 
 
Abbreviations: CD = cluster differentiation; cHL = classical Hodgkin lymphoma; Cy/Flu = cyclophosphamide and 
fludarabine; IA = interim analysis; IL = interleukin; NK = natural killer; PTCL = peripheral T-cell lymphoma; DL1 
= 2 × 109 cells at Day 1, Day 8 and Day 15; DL2 = 4 × 109 cells at Day 1, 2 × 109 cells at Day 8 and Day 15. 
The main aim of this study is to assess the antitumor activity of acimtamig in combination with 
AlloNK® in four cohorts of subjects: 
• Cohort 1: AlloNK® DL1 (2 × 109 cells on Day 1, Day 8, Day 15) + 200 mg acimtamig 
in classical HL (N: 6 to 61)  
• Cohort 2: AlloNK® DL1 + 300 mg acimtamig in classical HL (N: 6 to 61) 
• Cohort 3: AlloNK® DL2 (4 × 109 cells on Day 1; 2 × 109 cells on Day 8, Day 15) + 
200 mg acimtamig in classical HL (N: 6 to 61) 
• Cohort 4: AlloNK® DL2 + 300 mg acimtamig in classical HL (N: 6 to 61) 
 
 


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Two additional exploratory cohorts will be evaluated: 
• Cohort 5: CD30-positive PTCL (N: 20) (AlloNK® DL1 or DL2 + acimtamig at 200 mg 
or 300 mg)  
• Cohort 6: AlloNK® DL1 or DL2 in classical HL (N: up to 12)  
The total number of planned subjects is up to 166. All subjects will receive acimtamig in 
combination with AlloNK® (Cohorts 1-5) or AlloNK® alone (Cohort 6) up to 3 cycles as described 
in Section 6.  
The main part of the study will include subjects with classical HL and will follow a Simon two-
stage design, with two stages designed for each classical HL cohort selected following the safety 
run-in. 
The safety run-in will be utilized for the first 6 classical HL subjects in Cohort 1 and Cohort 2 
(parallel enrollment), with staggering of at least 12 days between Day -5 (start of lymphodepletion) 
of one subject to Day -5 (start of lymphodepletion) of the subsequent subject (included as part of 
the 12-day period is a 7-day observation period following administration of Day 1 treatment). For 
the first 3 subjects enrolled in each cohort, the safety run-in approach will be utilized to monitor 
treatment-related toxicities during the safety run-in observation period, defined as the time from 
the first dose of combination study treatment (acimtamig/AlloNK®) to Day 21 of the treatment 
cycle (C1D21). If a Grade 3 or Grade 4 acimtamig or AlloNK®-related treatment-emergent 
adverse event (TEAE) (meeting criteria as stipulated in Section 10.6) occurs during the safety run-
in observation period for the first 3 subjects, then another 3 subjects will be enrolled using the 
same staggered approach. If no more than one Grade 3 or 4 acimtamig or AlloNK®-related TEAE 
is observed in the first 6 subjects, then enrollment of the first 3 classical HL subjects in Cohort 3 
and Cohort 4 (parallel enrollment) will begin, using the same staggering approach outlined for 
Cohort 1 and Cohort 2. If no Grade 3 or 4 acimtamig or AlloNK®-related TEAEs are not observed 
in the first 3 subjects, then enrollment may continue without staggering in Cohort 1 and Cohort 2 
and enrollment of the first 3 classical HL subjects in Cohort 3 and Cohort 4 (parallel enrollment) 
will begin, using the same staggering approach as outlined for Cohort 1 and Cohort 2. Backfilling 
into Cohorts 1 and 2 will be allowed during the safety clearance period for Cohorts 3 and 4. 
 
 
 
 
 
  
An additional exploratory cohort (Cohort 5) will enroll subjects with CD30-positive PTCL. 
Cohort 5 will be hypothesis generating only, consisting of one part with a total of N=20 
CD30-positive PTCL subjects. This cohort will start enrollment after all classical HL cohorts have 
cleared the safety run-in (i.e., each subject enrolled in Cohort 1 to Cohort 4 have completed the 
safety run-in observation period). The planned dose level will be chosen from the two regimens 
selected for Stage 1 evaluation after analysis of the benefit-risk profile for each regimen. 
Another additional exploratory cohort (Cohort 6) will consist of up to 12 subjects with R/R HL for 
exploratory investigation of AlloNK® monotherapy in cHL. The planned dose of AlloNK® will be 
chosen from the regimen(s) selected for Stage 2. As such, this cohort will start enrollment at the 


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time of Stage 2 of the trial. 
 
 
 
 
   
An independent Safety Review Committee (SRC) will be established prior to the enrollment of the 
first subject. The independent SRC will be responsible for reviewing at regular intervals the safety 
data of all subjects throughout the conduct of the study. Detailed recruitment status and interim 
safety reports will be provided to the SRC on a regular basis. Further details regarding the 
constitution of the SRC and its specific roles and responsibilities and timing of reviews will be 
provided in the SRC charter.  
4.1. 
Study Periods 
This multi-center study will include a Screening Period, a Treatment Period, End of Treatment 
(EOT) visit, a Safety Follow-up visit, and a Long-Term Follow-Up Period.  
4.1.1. 
Screening Period 
The Screening Period lasts up to 28 days prior to Cycle 1 Day -5 (from Day -34 up to Day -5). The 
Screening Period begins when the Informed Consent Form (ICF) is signed and ends on the day 
before the first dose of lymphodepletion on Cycle 1 Day -5. Before entering the study, all study 
procedures and possible risks will be explained to each subject who is asked to participate in the 
study. After provision of written informed consent for the study, screening assessments will 
include a careful review of the subject’s medical history, assessment of Eastern Cooperative 
Oncology Group (ECOG) performance status (PS), physical examination, electrocardiogram 
(ECG), echocardiography, laboratory, and disease assessment, as specified in the Schedule of 
Assessments 
). For subjects with the diagnosis of 
PTCL a fresh tumor biopsy should be obtained during the Screening Period for retrospective 
confirmation of CD30 status, unless archival tissue/slides will be substituted (the specimen must 
be 90 days or younger from Cycle 1 Day -5), refer to Section 8.2 for further details. Subject’s 
laboratory assessments to confirm eligibility criteria (Section 5.1) must be confirmed before D-5 
of the treatment cycle (start of lymphodepletion). The assessments for hepatitis B, hepatitis C, and 
human immunodeficiency virus (HIV) do not need to be repeated for re-screened subjects if 
performed within 3 months before first dose of lymphodepletion (i.e., on Cycle 1 Day -5). Please 
review the inclusion criteria (Section 5.1) and exclusion criteria (Section 5.2) to see allowed time 
periods of screening assessments.  
4.1.2. 
Treatment Period 
Upon confirmation of study eligibility, the subjects will be defined as enrolled, and they will enter 
the Treatment Period which starts with the day of first dose of lymphodepletion on Cycle 1 Day-5 
and will receive study drugs according to their assigned dose level. Day 1 of every Cycle is the 
anchor for all timepoints in the specific cycle. 
The study drugs will be administered in 48-day cycles up to 3 cycles total as detailed in Section 6.1. 
Please refer to 
 
detailing all assessments and procedures to be completed during the Treatment Period 
throughout the study. 




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study drug (acimtamig and/or AlloNK®) if the subject withdraws their consent or 
the Sponsor decides to stop collecting this information. 
4.3. 
Study Initiation and Completion 
The start of this clinical study is defined as the first act of recruitment for a potential subject. 
The end of the study is defined as when the last subject ending treatment has completed the last 
visit, withdrawn consent, has been lost to follow-up, or has died. 


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5. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
Subjects will be considered eligible to be enrolled in the study if ALL the inclusion criteria and 
NONE of the exclusion criteria are met as defined below. Prospective approval of protocol 
deviations to recruitment and enrollment criteria, also known as protocol waivers or exemptions, 
is not permitted. 
5.1. 
Inclusion Criteria 
A subject is eligible to be included in the study only if ALL the following criteria apply: 
1. Subjects with a diagnosis of FDG-avid relapsed or refractory classical HL OR select 
subtypes of FDG-avid 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 (Note: Archival 
tissue may be substituted for a fresh tumor biopsy, please refer to Section 8.1 and the 
Schedule of Assessments (
) for additional details).  
PTCL subtypes 
• PTCL-NOS 
• Angioimmunoblastic T-cell lymphoma 
• ALCL, anaplastic lymphoma kinase (ALK)-positive 
• ALCL, ALK-negative 
2. Prior treatment for the disease under study consistent with the following: 
• 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 
(acimtamig and/or AlloNK®). 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 
drug (acimtamig and/or AlloNK®). 
3. Male or female aged ≥18 years (or as required by local regulation) on the day of signing 
the ICF. 
4. ECOG Performance Status (PS) 0 or 1. 
 


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5. Absolute neutrophil count ≥1000/mm3, hemoglobin ≥7 g/dL, and platelet count 
≥50,000/mm3. 
• Transfusions of packed red blood cells and platelets are allowed up to 
2 weeks prior to Day -5 of the first cycle and as needed during the Treatment 
Period. Growth factors are allowed during Screening up to 2 weeks prior to 
the first dose of lymphodepleting chemotherapy and as needed during the 
Treatment Period. All lab parameters should be checked within 2 days of 
the first dose of lymphodepleting chemotherapy to reassess eligibility. 
6. Adequate organ function defined by the following laboratory parameters during screening: 
• Direct (conjugated) bilirubin ≤2 × the upper limit of normal (ULN), or total 
bilirubin ≤3 × ULN if considered due to Gilbert’s disease AST and alanine 
aminotransferase (ALT) ≤3.0 × ULN, unless considered due to malignant 
disease involvement, in which case AST and ALT can be ≤ 5.0 × ULN. 
• Creatinine clearance (CrCl) ≥50 mL/min. Creatinine clearance will be 
calculated using the Cockcroft and Gault equation. 
• International normalized ratio (INR) <1.5 × ULN and activated partial 
thromboplastin time (aPTT) <1.5 × ULN (for subjects not receiving 
therapeutic anticoagulation) (Note: subjects receiving therapeutic 
anticoagulation may enroll with INR ≥1.5 × ULN).  
7. Adequate pulmonary function with forced expiratory volume (FEV1), forced vital capacity 
(FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for Hgb 
and volume) ≥50%. 
8. Adequate cardiac function with left ventricular ejection fraction ≥50% and no uncontrolled 
arrhythmias or symptomatic cardiac disease. 
9. Capable of giving signed informed consent that includes compliance with the requirements 
and restrictions listed in the ICF and in the study protocol. 
10. Female subjects must have a negative urine or serum pregnancy test within 7 days prior to 
first dose of lymphodepletion if of childbearing potential, or be of non-childbearing 
potential. If the urine pregnancy test is positive or cannot be confirmed as negative, a serum 
pregnancy test will be required. The serum pregnancy test must be negative for the subject 
to be eligible. Non-childbearing potential is defined as: 
• Postmenopausal, defined as no menses for 12 months without an alternative 
medical cause. A high follicle-stimulating hormone (FSH) level in the 
postmenopausal range may be used to confirm a post-menopausal state in 
women not using hormonal contraception or hormonal replacement therapy. 
However, in the absence of 12 months of amenorrhea, a single FSH 
measurement is insufficient.  
• Surgically sterile. Surgical sterilization methods include hysterectomy, 
bilateral salpingectomy, and bilateral oophorectomy. 
11. Females of childbearing potential must agree to sexual abstinence (defined below) or be 
willing to use a highly effective method of contraception for the course of the study from 
14 days prior to the first dose of lymphodepletion through 120 days after the last dose of 


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study drug (acimtamig and/or AlloNK®). Acceptable highly effective birth control methods 
include: 
• Oral, intravaginal, or transdermal combined (estrogen and progestogen 
containing) hormonal contraception associated with inhibition of ovulation;  
• Oral, injectable, or implantable progestogen-only hormonal contraception 
associated with inhibition of ovulation;  
• Intrauterine device;  
• Intrauterine hormone-releasing system;  
• Bilateral tubal occlusion;  
• Vasectomized partner (provided that partner is the sole sexual partner of the 
female of reproductive potential and that the vasectomized partner has 
received medical assessment of the surgical success); and  
• Sexual abstinence. 
In the context of this study, sexual abstinence is considered a highly 
effective method only if defined as refraining from heterosexual intercourse 
from 14 days prior to the first dose of lymphodepletion up to 120 days after 
the last dose of study drug (acimatamig and/or AlloNK®). The reliability of 
sexual abstinence needs to be evaluated in relation to the duration of the 
clinical study and the preferred and usual lifestyle of the subject. 
12. Males who have female partners of childbearing potential must agree to use a highly 
effective method of contraception as described in inclusion criterion 11, starting with the 
first dose of lymphodepletion through 120 days after the last dose of study drug 
(acimatamig and/or AlloNK®). 
5.2. 
Exclusion Criteria 
A subject is not eligible to enroll into the study if they have ANY of the following: 
1. Treatment within prior 3 weeks of Day 1 of treatment schedule (Cycle 1 Day 1) with any 
anti-cancer agent, investigational or approved. 
2. Continued toxicity from prior treatment that has not resolved to Grade ≤ 1, with allowable 
exceptions (e.g., alopecia). 
3. Active central nervous system (CNS) involvement (untreated or uncontrolled parenchymal 
brain metastasis or positive cytology of cerebrospinal fluid). 
4. Previous treatment with acimtamig or CBNK cells. 
5. Known hypersensitivity/allergic reaction ≥Grade 3 to monoclonal antibodies or any 
components used in the acimtamig product preparation, any history of anaphylaxis or 
uncontrolled asthma.  
6. History of a solid organ allograft, or an inflammatory or autoimmune disease likely to be 
exacerbated by IL-2 or other study specific treatment (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. 
Exceptions include any subject on 10 mg or less of prednisone or equivalent, subjects with 
vitiligo, hypothyroidism stable on hormone replacement, Type I diabetes, Graves’ disease, 
Hashimoto’s disease, alopecia areata, eczema, or psoriasis). 


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7. Treatment with any therapeutic mAb or immunosuppressive medications (such as high-
dose steroids defined as ≥10 mg prednisone or equivalent per day) within 4 weeks or 5 half-
lives (whichever is shorter) of Day 1 of treatment schedule. 
Exceptions for the use of corticosteroids: 
• Topical (≤20% of the skin surface area), ocular, intra-articular, intranasal, 
or inhalation corticosteroids with minimal systemic absorption. 
• Short course (≤ 7 days) of corticosteroids prescribed prophylactically (e.g., 
for contrast dye allergy or antiemetic therapy for specific chemotherapy) or 
for treatment of a non-autoimmune causes (e.g., delayed-type 
hypersensitivity reaction caused by contact allergen) as long as <10 mg 
prednisone equivalent. 
• Physiologic corticosteroid replacement therapy for adrenal or pituitary 
insufficiency. 
8. History of any other systemic malignancy, unless previously treated with curative intent 
and the subject has been disease free for 2 years or longer. Subjects who meet the above 
criteria and are on maintenance therapy for prior malignancy may be eligible after 
discussion and approval from the medical monitor. 
9. Live-virus vaccines given within 28 days prior to the initiation of study treatment. 
10. Active, uncontrolled infection requiring systemic therapy. If the infection is controlled or 
has resolved, maintenance and/or prophylactic systemic antimicrobials are permitted. 
11. Known active hepatitis B or hepatitis C as defined in the table below. Antiviral prophylaxis 
for chronic hepatitis B virus infection may be used at the discretion of the Investigator.  
Note: Subjects meeting following criteria are allowed to be enrolled in the study: 
 
Eligible 
HBV 
HB sAg (-) 
HB sAg (+) and HBV DNA <500 IU/mL (or 2500 copies/mL) 
HCV 
HCV Ab (-) 
HCV Ab (+) and HCV RNA (-) 
Abbreviations: HBV = hepatitis B virus; HBs Ag = HBV surface antigen; HCV = hepatitis C virus; 
HCV Ab = HCV antibody  
12. Active HIV infection as evidenced by a positive HIV polymerase chain reaction (PCR) test 
result. 
13. Active acute or chronic GVHD or GVHD requiring immunosuppressive treatment, 
clinically significant central nervous system (CNS) dysfunction (seizure disorder, 
dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy 
syndrome (PRES), autoimmune disease with CNS involvement).  
14. Any uncontrolled medical condition, including but not limited to: unstable angina pectoris, 
symptomatic congestive heart failure (New York Heart Association [NYHA] II, III, IV;, 
myocardial infarction ≤6 months prior to first dose of study drug (acimtamig and/or 
AlloNK®), uncontrolled cardiac arrhythmia e.g., atrial fibrillation/flutter, cerebrovascular 
accidents ≤6 months before first dose of study drug (acimtamig and/or AlloNK®).  
15. Major surgical procedure (i.e., any open surgical procedure that involves the resection or 
manipulation of major organ) or significant traumatic injury within 4 weeks before first 


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dose of study drug (acimtamig and/or AlloNK®) or anticipation of need of a major surgical 
procedure during the course of study. 
Note: Procedures that are considered to be minimally invasive (e.g., peripherally inserted 
central catheters lines and/or port placements, interventional biopsies) will be exceptions. 
16. Pregnant or breastfeeding women. Breastfeeding must be discontinued before onset of and 
during treatment and should be discontinued for at least 3 months after end of treatment. 
17. Substance abuse, medical, psychological, or social conditions that may interfere with the 
subject’s cooperation with the requirements of the study or evaluation of the study results. 
18. Any medical, psychological, or social condition that would interfere with the subject’s 
participation in the study. 
5.3. 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently confirmed as eligible to participate in the study. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure subjects to meet the 
Consolidated Standards of Reporting Trials publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any SAE. 
Subjects who do not meet the criteria for participation in this study for reversible reasons may be 
rescreened. A new subject number will be assigned upon screening (Note: Screening assessments 
that have not been performed within 28 days of Cycle 1 Day -5 for subjects who are rescreened 
must be repeated. The assessments for hepatitis B, hepatitis C, and HIV do not need to be repeated 
for re-screened subjects if performed within 3 months). 
5.4. 
Withdrawal of Subjects in the Study  
5.4.1. 
Withdrawal of Consent 
A subject may withdraw consent to participate in this study at any time without penalty or loss of 
benefits to which the subject is otherwise entitled. When a subject wishes to withdraw consent, it 
is important to distinguish between withdrawing his/her consent for a particular study procedure 
or visit versus withdrawing his/her consent from the study entirely (i.e., premature 
discontinuation). 
When a subject withdraws consent from the study (or study procedure), the reason(s) for 
withdrawal will be recorded by the Investigator or designee on the relevant page of the eCRF. 
5.4.2. 
Premature Discontinuation 
All subjects have the right to refuse further participation in the study at any time and for any reason. 
A subject’s participation must, therefore, be terminated immediately upon his/her request. 
Subjects can withdraw from treatment or participation in this study at any time, for any reason, 
specified or unspecified, and without prejudice. The reasons for study drug (acimtamig and/or 
AlloNK®) discontinuation or study withdrawal may include the following reasons: 
• Radiographic or symptomatic disease progression or disease relapse 


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• Unacceptable toxicity or any study treatment-related event that is deemed life-
threatening, regardless of grade 
• Investigator decision  
• Significant non-compliance with the study procedures by the subject, or the 
Investigator  
• Sponsor terminates the study 
• Pregnancy 
Subjects who are withdrawn from study treatment should complete the EOT visit, Safety Follow-
up visit and will enter into long-term follow-up for progression and survival status (
 
.  
5.5. 
Lost to Follow-up 
Study subjects will be considered lost to follow-up if they repeatedly fail to return for scheduled 
visits and are unable to be contacted by the study site. The following actions must be taken if a 
study subject fails to return to the clinic for a required study visit: 
• The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible and counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in the 
study. 
• Before a subject is deemed lost to follow up, the Investigator or designee must make every 
effort to regain contact with the subject (where possible, 3 telephone calls and, if necessary, 
a registered letter to the subject’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the subject’s medical record; and 
• Should the subject continue to be unreachable, he/she will be considered to have withdrawn 
from the study. 
Situations of non-compliance will be reviewed on a case-by-case basis with the Sponsor and the 
site will be provided guidance on subject withdrawal from treatment and/or the study, where 
appropriate. 
5.6. 
Replacement of Subjects 
During the safety run-in, subjects will be replaced if they have not received at least 66% of the 
AlloNK® and acimtamig combination during cycle 1. 
For the randomized stage 1 and stage 2 part of the study, replacement of a subject may be permitted 
only if a subject discontinues or withdraws prior to receiving both study drugs (i.e., acimtamig and 
AlloNK®). The same rule applies for the exploratory PTCL cohort (Cohort 5). 
For Cohort 6, subjects will be replaced if they have not received at least 66% of AlloNK® during 
cycle 1. 
 
 


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6. 
STUDY TREATMENTS 
6.1. 
Overview of Study Treatments and Administration 
The Investigator shall take responsibility for the study treatments and shall take all steps to 
maintain appropriate records and ensure appropriate supply, storage, handling, distribution, and 
usage of study treatments in accordance with the clinical study protocol and any applicable laws 
and regulations. 
Study treatments described in the sections below will be administered in 48-day cycles, up to 
3 cycles in total, with a 2-week rest period (+ 2 week) between each cycle as indicated in the 
Schedule of Assessments 
 refer also to Figure 2). On treatment days, after 
administration of all study drugs in the treatment regimen, subjects must be observed for at least 1 
hour. 
6.1.1. 
Lymphodepletion 
Prior to the administration of the first acimtamig and AlloNK® infusions in each cycle, a standard 
lymphodepleting regimen will be administered.  
Within 2 days prior to the start of each lymphodepletion regimen of each cycle, the absolute 
neutrophil count, hemoglobin, platelet count, bilirubin, AST, ALT, and creatinine clearance should 
be assessed for suitability to proceed: 
• Absolute neutrophil count ≥1000/mm3, hemoglobin ≥7 g/dL, and platelet count 
≥50,000/mm3. 
• Direct (conjugated) bilirubin ≤2 × ULN, or total bilirubin ≤3 × ULN if considered due to 
Gilbert’s disease, AST and ALT ≤3.0 × ULN, unless considered due to malignant disease 
involvement, in which case AST and ALT can be ≤ 5.0 × ULN. 
• CrCl ≥50 mL/min. Creatinine clearance will be calculated using the Cockcroft and Gault 
equation. 
NOTE: If a subject does not meet the minimum laboratory values for absolute neutrophil count, 
platelet count, bilirubin, AST, ALT, and creatinine clearance stated above, please refer to 
Section 6.3 for allowed dose delays and allowed supportive concomitant medications in 
Section 6.4.1.  
Intravenous cyclophosphamide (300 mg/m2/day) and fludarabine (30 mg/m2/day) will be 
administered daily for 3 consecutive days, starting 5 days before the first dose of acimtamig and 
AlloNK® (i.e., from Day -5 through Day -3). Lymphodepleting therapy may only be started if the 
laboratory values for hematology, renal and liver function meet the requirements of the inclusion 
criteria. Pre-medication should be administered per institutional guidelines but should not include 
steroids. 
 
 




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Subjects may also be administered prophylactic antiemetic medications as indicated.  
6.1.3. 
Acimtamig 
Acimtamig will be administered intravenously at a fixed dose of 200 mg or 300 mg on Day 1, Day 
8, and Day 15 of each cycle prior to administration of AlloNK®. Additionally, acimtamig will be 
administered as the sole therapy at a dose of 200 mg or 300 mg intravenously on Day 22, Day 29 
and Day 36 of each cycle. 
On the days that acimtamig is given in combination with AlloNK®, it will be given first, followed 
by a one-hour observation period. All doses of acimtamig will be infused at an initial infusion rate 
of 50 mg/h (level 1).
 
 
 
 
 
  
6.1.4. 
AlloNK® 
AlloNK® will be administered (as soon as practical after thawing but must be within 90 minutes 
after thawing) upon completion of administration and observation period for acimtamig. Subjects 
at DL1 will be administered a fixed dose of 2 × 109 cells IV on Day 1, Day 8 and Day 15 of each 
cycle. Subjects at DL2 will be administered a fixed dose of 4 × 109 cells IV on Day 1, then 2 x 109 
cells/dose on Days 8 and 15. Those subjects who initially consented under protocol v3.0 and later 
versions and thus will not receive IL-2 after the AlloNK® treatment, the observation period will 
end 1-hour after the AlloNK® infusion on Day 1, Day 8, or Day 15 of every Cycle if AlloNK® is 
given.   
Refer to the AB-101 Storage, Preparation, and Administration Manual for additional information 
on storage, preparation, and administration. 
6.1.5. 
IL-2 
IL-2, dosed at 6 × 106 IU, will be administered to all subjects who initially consented under 
protocol v2.0 subcutaneously, at least 1 hour and no more than 4 hours following the conclusion 
of each AlloNK® dose. IL-2 administration is followed by a 1-hour observation period. Those 
subjects who initially consented under protocol v3.0 and later versions will not receive IL-2 after 
the AlloNK® treatment. For subjects under treatment with IL-2 experiencing IL-2 related adverse 
events, subsequent IL-2 administrations can be stopped.   
Refer to the PROLEUKIN® (aldesleukin) USPI for additional information on storage, preparation, 
and administration. 
6.2. 
Assignment of a Study Number and Dose Level 
6.2.1. 
Assignment of a Subject Number 
At the Screening Visit, each subject will have a unique subject identification (ID) number assigned 
for subject identification. 


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For subjects that are rescreened (Section 5.3), a new subject number will be assigned upon 
rescreening. 
6.2.2. 
Assignment to a Cohort and Dose Level  
Once eligibility has been confirmed by the Investigator, sites must submit a subject eligibility 
packet to the Medical Monitor for review. After Medical Monitor approval to proceed with 
enrollment, subjects will be enrolled first into Cohorts 1 and 2 in parallel (alternating between 
Cohort 1 and Cohort 2). Upon safety clearance of Cohorts 1 and 2, subjects will be enrolled in 
parallel into Cohorts 3 and 4 (alternating between Cohort 3 and Cohort 4). Backfilling into cohorts 
1 and 2 will be allowed during the safety clearance period for Cohorts 3 and 4. After the safety 
run-in is completed for Cohorts 1 to 4, classical HL subjects will be randomized thereafter into the 
two selected cohorts for further evaluation in the Simon two-stage design part of the study (refer 
to Section 4 and Figure 2). After the safety run-in is completed for Cohorts 1 to 4, CD30-positive 
PTCL subjects will be enrolled sequentially into the exploratory Cohort 5. Cohort 6 will be started 
during Stage 2 of the trial. 
6.3. 
Dose Modification, Delays, or Interruptions 
Permitted windows for study specific treatment administration are provided in the Schedule of 
Assessments (
 
Study drug dosing delays may be permitted in the case of medical/surgical events or logistical 
reasons not related to study therapy (e.g., elective surgery, unrelated medical events, subject 
vacation and/or holidays) after obtaining approval from the Sponsor. 
Dose management may be required for subjects to recover from treatment-emergent toxicities and 
return to baseline or Grade 2 and are permitted as specified in Section 6.3.1 for acimtamig and 
Section 6.3.2 for AlloNK®. Management and grading of IRRs and CRS events and provided in 
Section 6.3.4. 
A maximum of 3 days is allowed for a treatment/dose delay of acimtamig, AlloNK® or the 
combination during an individual cycle. If the dose delay is 3 days or less, then the individual cycle 
should continue as scheduled with the appropriate intervals between subsequent doses should 
clinical status allow. If the dose delay is 4 or more days, then the dose should be omitted and the 
subsequent doses/treatment should be administered per the individual cycle plan if clinical status 
allows. The re-initiation of study drugs after a treatment delay of > 7 days will require prior 
authorization from the Medical Monitor. 
A two-week rest period is planned between each treatment cycle. In general, dose delays of up to 
an additional 2 weeks (≤14 days) are allowed between completion of one cycle and start of the 
next cycle, for subjects to recover from any AE and return to baseline or ≤Grade 2. Re-initiation 
of study treatment should be discussed with and approved by the Medical Monitor.  
6.3.1. 
 
 
 
 
 






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Table 3: 
Grading System for IRR and related Events  
CTCAE Term 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Infusion related 
reaction 
Mild transient 
reaction; infusion 
interruption not 
indicated; intervention 
not indicated 
Therapy or infusion 
interruption indicated 
but responds promptly 
to symptomatic 
treatment (e.g., 
antihistamines, 
NSAIDS, narcotics, IV 
fluids); prophylactic 
medications indicated 
for ≤24 hours 
Prolonged (e.g., not rapidly 
responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms 
following initial 
improvement; 
hospitalization indicated for 
clinical sequelae 
Life-threatening 
consequences; urgent 
intervention indicated 
 
Death 
Definition: A disorder characterized by adverse reaction to the infusion of pharmacological or biological substances. Clinically it presents with tachypnea, 
headache, tachycardia, hypotension, rash, chills, fever and/or hypoxia 
Navigational Note: - If related to infusion, use Injury, poisoning, and procedural complication: Infusion related reaction. Do not report both 
Allergic reaction 
Systemic intervention 
not indicated 
Oral intervention 
indicated 
Bronchospasm; 
hospitalization indicated for 
clinical sequelae; 
intravenous intervention 
indicated 
Life-threatening 
consequences; urgent 
intervention indicated 
Death 
Definition: A disorder characterized by an adverse local or general response from exposure to allergen. 
Anaphylaxis 
- 
- 
Symptomatic 
bronchospasm, with or 
without urticaria; parenteral 
intervention indicated; 
allergy related 
edema/angioedema; 
hypotension 
Life-threatening 
consequences; urgent 
interventions indicated  
Death 
Definition: A disorder characterized by an acute inflammatory reaction resulting from the release of histamine and histamine-like substances from mast cells, 
causing a hypersensitivity immune response. Clinically, it presents with breathing difficulty, dizziness, hypotension, cyanosis and loss of consciousness, and 
may lead to death. 


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Table 4: 
Grading System for CRS and Neurotoxicity (ASTCT Grading and ASTCT ICANS Grading)  
ASTCT 
Grading Term  
Grade 1 
Grade 2 
Grade 3 
 
 
Grade 4 
Grade 5  
Cytokine release 
syndrome: 
Fever with,  
 
 
 
 
Temperature 
≥38  C, 
 
 
Temperature 
≥ 38 °C 
 
 
Temperature ≥ 38  C 
 
 
Temperature ≥ 38  C 
Death 
Hypotension 
and/or 
 
No 
Hypotension  
 
Hypotension 
responding to 
fluids;  
 
Hypotension managed with 
one vasopressor with or 
without vasopressin;  
 
Requiring multiple vasopressors 
(excluding vasopressin) 
 
 
Hypoxia 
No hypoxia 
 
Requiring low-
flow nasal 
cannula or blow-
by 
 
Requiring high-flow nasal 
cannula, facemask, 
nonrebreather mask, or 
Venturi mask 
 
Requiring positive pressure (e.g., CPAP, 
BiPAP, intubation and mechanical 
ventilation) 
Definition: A disorder characterized by fever, tachypnea, headache, tachycardia, hypotension, rash, and/or hypoxia caused by the release of cytokines. 
Navigational Note:  
 
Organ toxicities associated with CRS may be graded according to CTCAE v5.0 but they do not influence CRS grading.  
 
Fever is defined as temperature 38 °C not attributable to any other cause. In subjects who have CRS then receive antipyretic or anticytokine therapy 
such as tocilizumab or steroids, fever is no longer required to grade subsequent CRS severity. In this case, CRS grading is driven by hypotension 
and/or hypoxia.  
 
CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. For example, a subject with 
temperature of 39.5 °C, hypotension requiring 1 vasopressor, and hypoxia requiring low-flow nasal cannula is classified as Grade 3 CRS. 
 
Low-flow nasal cannula is defined as oxygen delivered at ≤ 6 L/minute. Low flow also includes blow-by oxygen delivery, sometimes used in 
pediatrics. High-flow nasal cannula is defined as oxygen delivered at >6 L/minute 


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ASTCT ICANS Grading  
NOTE: ICANS/Neurotoxicity should be evaluated and managed according to institutional Standard of Care 
Neurotoxicity 
Domain 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
ICE score 
7-9 
3-6 
0-2 
0 (Subject is unarousable and unable to 
perform ICE) 
Death 
Depressed level 
of consciousness 
Awakens 
spontaneously 
Awakens to 
voice 
Awakens only to tactile 
stimulus 
Subject is unarousable or requires vigorous 
or repetitive tactile stimuli to arouse. 
Stupor or coma 
Seizure 
Not applicable 
Not applicable 
Any clinical seizure focal or 
generalized that resolve 
rapidly or nonconvulsive 
seizures on EEG that resolve 
with intervention 
Life threatening prolonged seizure 
(>5min); or repetitive clinical or electrical 
seizures without return to baseline in 
between 
Motor findings 
Not applicable 
Not applicable 
Not applicable 
Deep focal motor weakness such as 
hemiparesis or paraparesis  
Elevated ICP/ 
cerebral edema 
Not applicable 
Not applicable 
Focal/local edema on 
neuroimaging 
Diffuse cerebral edema on neuroimaging 
decerebrate or decorticate posturing; or 
cranial nerve VI palsy; or papilledema; or 
Cushing´s triad  
 Definition: Psychiatric disorders: Hallucinations or Confusions; Nervous system disorders: Seizure, Dysphasia, Headache 
Definition of ICE score as Encephalopathy assessment Tool: 
Orientation: 4 points; Naming: 3 points; Following commands: 1 point; Writing a standard sentence: 1 point; Attention/Counting backwards: 1 point 
Scoring: 10, no impairment; 7-9, Grade 1 ICANS; 3-6, Grade 2 ICANs;0-2, Grade 3 ICANS; 0, Grade 4 ICANS  
Depressed level of consciousness should be attributable to no other cause (e.g., no sedating medication).  
Tremors and myoclonus associated with immune effector cell therapies may be graded according to CTCAE v5.0, but they do not influence ICANS grading.  
Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is excluded from ICANS grading. It may be graded 
according to CTCAE v5.0. 
Abbreviations: ASTCT = American Society for Transplantation and Cellular Therapy; BiPAP =  bilevel positive airway pressure; CPAP = continuous positive 
airway pressure; CRS = cytokine release syndrome; CTCAE = Common Terminology Criteria for Adverse Events; ICANS = immune effector cell-associated 
neurotoxicity syndrome; ICE = immune effector cell-associated encephalopathy ; ICP = intracranial pressure. 
 


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Table 5: 
Clinical Grading of Acute GVHD (MAGIC Criteria) 
Overall clinical grade (based upon most severe target organ involvement): 
Grade 0 
No stage 1–4 of any organ 
Grade 1 
Stage 1–2 skin without liver, upper GI or lower GI involvement 
Grade 2 
Stage 3 rash and/or stage 1 liver and/or stage 1 upper GI and/or stage 1 lower GI 
Grade 3 
Stage 2–3 liver and/or stage 2–3 lower GI, with stage 0–3 skin and/or stage 0–1 upper GI 
Grade 4 
Stage 4 skin, liver or lower GI involvement, with stage 0–1 upper GI 
 
 
 
 
 
Stage 
Skin (active erythema only) 
Liver (bilirubin) 
Upper GI 
Lower GI (stool output/day) 
0 
No active (erythematous) GVHD 
rash 
< 2 mg/dl 
No or intermittent nausea, vomiting 
or anorexia 
Adult: 
< 
500 
ml/day 
or 
<3 
episodes/day 
Child: < 10 ml/kg/day or <4 
episodes/day 
1 
Maculopapular rash 
2–3 mg/dl 
Persistent 
nausea, 
vomiting 
or 
anorexia 
Adult: 500–999 ml/day or 3–4 
episodes/day 
<25% BSA 
Child: 10–19.9 ml/kg/day or 4–6 
episodes/day 
2 
Maculopapular rash 
3.1–6 mg/dl 
- 
Adult: 1000–1500 ml/day or 5–7 
episodes/day 
25 – 50% BSA 
Child: 20 – 30 ml/kg/day or 7–10 
episodes/day 
3 
Maculopapular rash 
6.1–15 mg/dl 
- 
Adult: 
>1500 
ml/day 
or 
>7 
episodes/day 
> 50% BSA 
Child: > 30 ml/kg/day or >10 
episodes/day 
4 
Generalized erythroderma (>50% 
BSA) plus bullous formation and 
desquamation > 5% BSA 
>15 mg/dl 
- 
Severe abdominal pain with or 
without ileus, or grossly bloody stool 
(regardless of stool volume). 
Abbreviations: BSA = body surface area; GI = gastrointestinal; GVHD = graft versus host disease. 
Source: Adapted from the Mount Sinai Acute GVHD International Consortium (MAGIC) criteria (Harris 2016). 










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6.4. 
Concomitant Medications 
Any medication (other than those excluded by the study protocol) that is considered necessary for 
the subjects’ welfare may be given at the Investigator’s discretion. Supportive medications will be 
reported in the eCRF with their reason for prescription, start and end date, route of administration, 
and daily dose. If a subject requires treatment with a prohibited medication (Section 6.4.2), this 
should be discussed with the Medical Monitor. 
6.4.1. 
Permitted Medications 
• Short term treatment (i.e., <1 week) with low doses (e.g., <10 mg prednisone equivalent) 
of systemic corticosteroids when medically necessary for the control of acute symptoms  
• Red blood cell and platelet transfusions per institutional guidelines. 
• Growth factors (e.g., granulocyte-colony stimulating factor [G-CSF]) may be considered 
during study treatment for subjects who develop neutropenia along with fever and/or 
infection, or who are considered at high risk of developing a life-threatening infection, 
according to the institutional standard of care. Growth factors and pegylated G-CSF must 
be stopped 7 and 14 days, respectively, prior to the bone marrow aspiration in the absence 
of an urgent medical need for continuing G-CSF administration.  
• Antibiotics (e.g., quinolone), antifungals, and antivirals may be used as standard of care 
for the prevention or treatment of infections. 
• Immunoglobulins should be administered with caution at the discretion of the Investigator. 
Immunoglobulins should not be administered within 3 days of any study drug (acimtamig 
and/or AlloNK®) administration.  
• Palliative radiotherapy for emergency treatment of complications of the disease under 
study is allowed provided the irradiated tumor site is not the only tumor manifestation. 
However, may not be given concomitantly with study treatments. 
6.4.2. 
Prohibited Medications 
• Subjects may not receive concomitant chemotherapy, immunotherapy, non-emergent 
radiotherapy, transplant, or any ancillary therapy that is not specified in the protocol, or 
that is considered to be investigational (i.e., used for non-approved indications(s) and in 
the context of a research investigation) while on study treatment. 
 
 
 
 
 
 
 
 
 
 


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6.5. 
Blinding and Procedures for Unblinding the Study 
This is an open-label study; there are no procedures for blinding and unblinding. 


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7. 
STUDY DRUG MATERIALS AND MANAGEMENT 
7.1. 
Study Drug Materials  
Acimtamig and AlloNK® are investigational medicinal products, the storage, preparation, and 
administration of which are summarized in the section below and will be described in more detail 
in their respective pharmacy manuals. 
The other study drugs (see Section 6.1) will be supplied from commercial sources or provided by 
the Sponsor. The Investigators should refer to the respective package inserts for information on 
use and administration. 
7.1.1. 
Acimtamig Investigational Product, Labeling, Storage, and Handling  
Acimtamig drug product is an injection intended to be used for i.v. infusion. 
The Sponsor will supply acimtamig study drug as a sterile lyophilized powder for reconstitution 
for intravenous (IV) infusion.  
Acimtamig study drug will be labeled as required per country requirement. Acimtamig vials 
containing drug product must be stored at 2 °C to 8 °C (36 °F – 46 °F). Acimtamig will be shipped 
to the site and must be stored at the site in a secure location under controlled conditions and in the 
required temperature range.  
Acimtamig infusions should be prepared on the day of dosing and used immediately after 
preparation. If not administered immediately, the acimtamig infusions (diluted drug product) 
should be stored ≤24 hours at 2 °C to 8 °C (36 °F – 46 °F). If necessary, the infusion solution is 
stable for up to 24 hours at room temperature (≤ 25°C / ≤77°F), however the accumulated time for 
storage, warm-up and infusion must not exceed 24 hours. In case of cold storage, a warm-up time 
of at least 30 minutes should be allowed before the start of infusion.  
Please refer to the current version of the acimtamig IB for information on the physical, chemical, 
and pharmaceutical properties of acimtamig. 
7.1.2. 
AlloNK® Investigational Product, Labeling, Storage, and Handling  
AlloNK® drug product is an injection intended to be used for i.v. infusion. 
AlloNK® is comprised of ex vivo-expanded allogeneic CBNK cells cryopreserved in an infusion-
ready suspension medium.  
 
 
 
 
 
 
 
 
 
 
 
 
 


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7.2. 
Accountability 
The Investigator is obliged to keep sufficient documentation of the delivery, use, and destruction 
or return of unused, used, or partially used study drug. The documentation must include dates, 
quantities, subject numbers, batch numbers, or other identification number. The Investigator may 
assign some or all of the Investigator’s duties for drug accountability to an appropriate pharmacist. 
Roles and responsibilities of site staff will be recorded in the Investigator Site File. 
The Investigator should maintain records that document adequately that the subjects were 
administered the doses specified in the protocol and reconcile all study drug received for the study. 
The local Clinical Research Associate (CRA) will be responsible for checking the drug 
accountability records maintained by the site during study monitoring visits. 
Study drug provided for this study is for use only as directed in the protocol. It is the Investigator 
and their institution’s responsibility to establish a system for handling study drug so as to ensure 
that: 
• Deliveries of study drug are correctly received by a responsible person; 
• Such deliveries are recorded; 
• Study drug is handled and stored safely and properly as stated on the label; 
• Study drug is only dispensed to study subjects in accordance with the protocol; and 
• Any unused study drug is destroyed locally or returned for destruction in liaison with the 
CRA after written approval by the Sponsor. 
Certificates of delivery and return must be signed by the responsible pharmacist or delegate and 
copies retained in the Pharmacy File. Throughout the study, it must be possible to reconcile 
delivery records with records of usage and any destroyed/returned stock of study drug. To help 


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with compliance checks, records of usage should include an appropriate form of identification of 
the subject to whom the study treatment was dispensed (using an indirect form to allow cross 
reference to the subjects’ identity), plus the quantity and date of dispensing. 
The return or destruction of unused drug will be conducted after written approval by the Sponsor, 
with appropriate documentation and drug accountability procedures completed following 
destruction. 
7.3. 
Treatment Compliance 
Administration of study drug will be supervised by the Investigator or sub-Investigator. Any 
delegation of this responsibility must follow the standard operating procedures. 
All subjects will be dosed at the site; thus, they will receive study drug directly from the 
Investigator or designee, under medical supervision. The date, time, and total amount delivered of 
each dose administered in the clinic will be recorded in the source documents and recorded in the 
eCRF. Should the total amount of study drug not be delivered or there is an interruption to dosing, 
the reason(s) and any associated AEs will be recorded in the source documents and recorded in the 
eCRF. 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
The planned application of the study medication, the study procedures and study evaluations for 
efficacy, safety and tolerability assessments as well as translational research evaluations are 
summarized in the Schedule of Assessments 
 
8.1. 
Confirmation of CD30-positive PTCL  
Histological confirmation of CD30-positive PTCL by locally assessed Ber-H2 targeted IHC is 
required for study participation (Section 5.1). In addition, CD30-positive PTCL will be assessed 
centrally for retrospective confirmation of CD30-positivity using Ber-H2 targeted IHC. 
The following criteria must be met to confirm CD30-positivity: 
• CD30 detected in ≥1% of neoplastic cells;  
• Total lymphocytes may be used only if enumeration of neoplastic cells is not 
feasible; this must be clearly documented by the local pathologist; 
• CD30 staining at any intensity above background; and membranous, cytoplasmic, 
and/or Golgi pattern of expression of the CD30 antigen. 
8.2. 
PTCL Tumor Procurement 
Four to ten (4-10) unstained slides from a fresh tumor biopsy will be required (mandatory) to be 
submitted to the Sponsor, or their selected vendor, for CD30 expression confirmation in PTCL 
subjects (Section 8.1). If archival tissue/slides will be substituted for a biopsy, the specimen must 
be collected not more than 90 days before Cycle 1 Day -5 and must be from a malignant node or 
extra-nodal tissue (including bone marrow) obtained by excisional/incisional or core biopsy. Fine 
needle aspirate or cytology samples will not be acceptable. Cutaneous biopsies will not be 
accepted. 
During the study, new lesions suspicious for relapse or progression will be considered in all 
subjects for biopsy as clinically indicated or to confirm response. Biopsies will be used for the 
below-mentioned analyses (Section 8.6.1), to better understand resistance mechanism related to 
the drug treatments after obtaining subject consent for optional analysis.  
Residual blood and biopsy samples will be stored to enable investigational research questions that 
may arise in the future to help gain information in understanding the cancer and/or the actions of 
the study treatments.  
The Sponsor may decide at any point during the trial to suspend or terminate exploratory biomarker 
assessments. 
8.3. 
Efficacy Assessments 
Disease and efficacy assessments will be conducted at Screening and on Day 43 (± 3 days) of each 
cycle, regardless of any treatment/cycle delays that may occur, as indicated in the Schedule of 
Assessments 
  
Response assessment will follow the Lugano classification (Cheson 2014; 
 for 
definition of CR, complete metabolic response (CMR), PR, partial metabolic response (PMR), 


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progressive disease , and progressive metabolic disease (PMD). Subjects who achieve a response 
and proceed to receive subsequent transplant will be followed for progression and survival status. 
Assessments utilizing PET-CT will be performed both locally and centrally. Treatment decisions 
should be based on the local disease assessment.  
At the discretion of the investigator, subjects with the assessment of “indeterminate” response on 
PET/CT and no clinical evidence of progression, may continue to receive treatment on study 
pending further evaluation to confirm true progression versus pseudoprogression. 
8.4. 
Safety and Tolerability Assessments 
Safety and tolerability will be assessed by monitoring and recording of all AEs graded by the NCI 
CTCAE v.5.0 (including neurotoxicities that are not considered ICANS) except for CRS and 
ICANS which will be graded according to the ASTCT grading (Table 4), TLS will be graded 
according to the Cairo-Bishop TLS grading system (Appendix H) and acute GVHD will be grading 
according to the MAGIC criteria (Table 5). For further details on severity grading, please refer to 
Section 10.2.1. The time points for the different study assessments related to safety and tolerability 
are listed in the Schedule of Assessments (
  
8.4.1. 
Medical History 
There will be a baseline assessment of relevant medical history conducted at Screening to confirm 
eligibility and to record significant medical history and concurrent illnesses in the eCRF. 
Concurrent illnesses recorded at Screening (excluding the primary disease under evaluation), that 
worsen in severity or frequency from this baseline assessment during the study, should be reported 
as AEs (see Section 10). 
8.4.2. 
Pregnancy and Follicle Stimulating Hormone Tests 
Female subjects of reproductive potential will be required to have a pregnancy testing during study 
participation. The first pregnancy test must be carried out within 7 days prior to the first dose of 
lymphodepletion. Subsequent tests are required for each cycle within 7 days before the start of 
lymphodepletion, on Day 1 and Day 29 of each cycle during the Treatment Period, and at the EOT 
visit 
 A urine test is acceptable; however, where a urine test is equivocal, a blood 
test must be performed to confirm the result. Subjects confirmed as pregnant will be excluded from 
participation in the clinical study. 
Female subjects who require documented confirmation of post-menopausal status will have their 
FSH levels assessed at Screening. A urine test is acceptable; however, where a urine test is 
equivocal, a blood test must be performed to confirm the result. Where post-menopausal status is 
not confirmed, subjects will be required to undergo pregnancy testing per protocol to confirm 
suitability to proceed. 
8.4.3. 
Eastern Cooperative Oncology Group Performance Status 
ECOG PS will be assessed at the times given in Schedule of Assessments 
 Details 
of the ECOG PS categories are presented in 
 Subjects must be confirmed as ECOG 
PS 0 or 1 at Screening to be eligible for study participation (Section 5.1). 


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8.4.4. 
Vital Signs 
Vital sign parameters will be taken at the times given in Schedule of Assessments (
 
The date and time of collection will be recorded in the source data and in the eCRF. 
Vital sign parameters will consist of measurements of temperature, resting heart rate, seated blood 
pressure (systolic/diastolic) and respiratory rate. 
If any clinically significant findings are identified during the study, the Investigator will record 
these as an AE, where the finding represents a change from baseline. 
8.4.5. 
Physical Examinations 
A physical examination, including measurement of weight, will be taken at the times given in 
Schedule of Assessments 
 The subject’s height will be measured at Screening. The 
subject’s weight will also be assessed at Screening and prior to each acimtamig administration. 
Height and body weight will be obtained while the subject is wearing light clothing (without 
shoes). 
A full physical examination will include assessment of the following categories: head, eyes, ears, 
nose, throat, heart, lungs, abdomen, skin, musculoskeletal, extremities, neurological, lymph nodes, 
and ‘other’. After the Screening assessment, the physical examination may be reduced to a 
symptom-directed assessment. 
If any clinically significant findings are identified during the study, the Investigator will record 
these as an AE, where the finding represents a change from baseline. 
8.4.6. 
Clinical Chemistry, Hematology, Coagulation, and Urinalysis 
Blood and urine samples for determination of clinical chemistry, hematology, and urinalysis 
parameters will be taken at the times given in Schedule of Assessments (
 and recorded 
in the source data and in the eCRF. Coagulation will be assessed at Screening and EOT visit only 
and may be assessed from the hematology sample. 
The laboratory variables to be measured are described in 
 
Copies of laboratory accreditation certificates and reference ranges will be obtained from each 
study site prior to analysis of their first subject sample and maintained over the course of the study. 
If any clinically significant findings are identified during the study, the Investigator will record 
these as an AE, where the finding represents a change from baseline. 
8.4.7. 
Electrocardiogram 
A resting 12-lead ECG will be performed at the times given in Schedule of Assessments 
  
All 12-lead ECGs should be recorded while the subject is in the supine position. ECGs will be 
recorded at 25 mm/sec. All efforts should be made to ensure that an identical ECG machine is used 
to collect traces for individual subjects. The Investigator or designated physician will review the 
ECG results. If any clinically significant findings are identified during the study, the Investigator 
will record these as an AE, where the finding represents a change from baseline. 


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8.5. 
Pharmacokinetic Sampling 
All subjects will be required to participate in PK sampling in the study, and serial blood samples 
will be collected and analyzed at specified times for measurement of acimtamig and AlloNK® 
  
The nominal PK blood sampling times requested should be adhered to as closely as possible. It is 
essential that the actual date and time of collection of each blood sample is recorded in the subject’s 
records and in the eCRF. 
8.6. 
Additional Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
8.6.2. 
Anti-drug Antibodies 
All subjects will have blood samples taken to assess anti-drug antibodies (ADAs) at the time points 
described in Schedule of Assessments 
).  
8.6.3. 
Quality of Life Assessment  
Evaluation of QoL parameters will be performed at the time points described in Schedule of 
Assessments (
).  
Subjects will be evaluated utilizing EORTC QLQ-C30, an example is provided in 
 


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8.7. 
Volume of Blood Sampling 
Total blood volumes required during study participation will be provided in the ICF provided to 
each subject. Efforts will be made to limit blood sampling and to avoid any redundancy. 
Residual blood samples may be stored and used as the basis for additional exploratory analysis 
after the study to help gain information in understanding HL, PTCL or other hematological 
malignancies and/or the actions of the study treatments. 
 


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9. 
STATISTICAL METHODS AND DATA ANALYSIS 
The Statistical Analysis Plan (SAP) will be developed and finalized before database lock. This 
section is a summary of the planned statistical analyses. Detailed statistical analysis information 
will be provided separately in the SAP, which will also outline protocol deviation criteria. Any 
deviations to the planned analyses specified or populations defined within the SAP will be justified 
in writing and presented within the final clinical study report (CSR). 
The clinical database lock will occur after all data are reconciled (i.e., “cleaned”) for all subjects 
who receive at least one dose of acimtamig and AlloNK®. A single CSR will be generated for this 
study. 
An addendum (or addenda) to the CSR will be generated as required to report any data obtained 
during the Follow-up Assessments. 
The study will have six separate cohorts, which will be analyzed independently as described below. 
Those subjects who initially consented under protocol v3.0 and later versions, and thus will not 
receive IL-2 after the AlloNK® treatment, will be analysed separately. 
9.1. 
Analysis Sets 
The safety analysis set (SAS) will consist of all subjects who received any amount of any 
component of the regimen (acimtamig, AlloNK® or any study treatment such as lymphodepletion 
or IL-2). The SAS will be the primary population for all safety-related endpoints.  
Following the ITT principle, the full analysis set (FAS) will consist of all subjects enrolled into 
one of the two selected cHL Cohorts in Stage 1 and Stage 2 or the exploratory PTCL Cohort 
(Cohort 5), who received at least 1 dose of both acimtamig and AlloNK®. The FAS will be the 
primary population for all efficacy related endpoints. 
Following the ITT principle for analysis of Cohort 6, the NK full analysis set (NK-FAS) will 
consist of all subjects who received at least 1 dose of AlloNK® in Cohort 6. The NK-FAS will be 
the primary population for all efficacy related endpoints concerning Cohort 6. 
The per protocol set (PPS) will consist of all subjects in FAS who did not have any major protocol 
deviations. The primary analysis will be repeated to support the results of the primary analysis on 
the FAS. 
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 acimtamig and AlloNK® combination dose during Cycle 1. 
The acimtamig PK set consists of all subjects (except those from Cohort 6) who have received at 
least 1 dose of acimtamig and have at least 1 post dose acimtamig PK measurement. 
The AlloNK® PK set consists of all subjects who have received at least 1 dose of AlloNK® and 
have at least 1 post dose AlloNK® PK measurement. 
Subjects who were screened and have signed the informed consent but did not receive any 
treatment will be listed including reason for screening failure and any SAE that is related to study 
procedure. These subjects will not be part of any summary table except for summarizing 
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Further populations might be explored and the final populations for analyses will be specified in 
the SAP. 
9.2. 
Sample Size Determination 
After the exhaustion of initial chemo, brentuximab vedotin (BV) and PD1 inhibitor 
(pembrolizumab, nivolumab) therapies, options for the heavily pretreated cHL patients are limited 
and largely palliative in nature and therefore patients should be included into clinical trials 
(Hanel 2022). 
Single agent or combination chemotherapy regimens recommended by the NCCN guideline 
Version 2.2013, such as bendamustine (Moskowitz 2013), gemcitabine + oxaliplatin 
(Gutierrez 2014), or bendamustine + carboplatin + etoposide (Budde 2018), as well as non-
chemotherapeutic targeted options such as lenalidomide (Fehninger 2011) and everolimus 
(Johnston 2010) have shown activity in r/r cHL patients.  
All studies cited above were uncontrolled Phase 1/ 2 or 2 studies with small sample size. 
Importantly, patients had not been pretreated with BV and PD1 inhibitor, thus do not reflect the 
target population of the proposed study AFM13-203.  
The Phase 1/2 single-center study AFM13-104 enrolled subjects with r/r cHL (n=41) that were 
treated with multiple lines of systemic therapy including BV and PD1 inhibitor – a study 
population that is comparable to that of AFM13-203. The study reported no responses to the 
immediate prior therapy before study inclusion (Nieto ASH 2022). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Cohort 5 (CD30-Positive PTCL) 
Due to the exploratory nature of Cohort 5, a sample size of N=20 is planned, to assess preliminary 
efficacy, safety and PD data and allow for hypotheses generation for follow up studies. 
Cohort 6 (cHL) 
Due to the exploratory nature of Cohort 6, a sample size of up to 12 subjects is planned to assess 
the efficacy and safety of AlloNK® given as monotherapy. 
9.3. 
Randomization 
The two selected cHL Cohorts in Stage 1 and Stage 2 of the trial will be randomized. The details 
about the randomization will be described in a separate document. Cohorts 5 and 6 will not be 
randomized. 
9.4. 
Demographic, Medical History, Prior Medication and Other Baseline 
Characteristics 
Demographic and tumor characteristics, prior anti-cancer therapies and surgeries, medical history, 
prior medication and other baseline data will be listed and summarized using descriptive statistics 
for continuation data and contingency tables for categorical data. Prior medication/Prior anti-
cancer therapies will be coded by World Health Organization (WHO) Anatomical, Therapeutic, 
and Chemical (ATC) terms. Medical history will be coded utilizing corresponding Medical 
Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and PTs. 
9.5. 
Study Drug 
The number of doses of acimtamig and AlloNK® administered over the entire study period will be 
listed and summarized using descriptive statistics. The time on acimtamig or AlloNK® until last 
treatment received will be listed and presented by descriptive statistics. 
9.6. 
Concomitant Medication 
Concomitant medication and significant non-drug therapies after the start of acimtamig or 
AlloNK® will be listed and summarized by WHO ATC terms in contingency tables. 
 
 
 
 
 
 
 
 
 
 
  


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9.7.1. 
ORR by IRC for Cohort 6 
The ORR by IRC for Cohort 6 is based on the ORR (CR + PR) assessed by IRC according to the 
Lugano classification (Cheson 2014; 
 and will be analyzed in a similar way as 
described above, but on the NK-FAS. Furthermore, subjects who do not develop a response (at 
least PR) after cycle 1 (i.e., after the first assessment) will be counted as treatment failures.  
The ORR will be presented as percentage rate including the 95% confidence interval. In addition 
to the ORR, the CRR and PRR will be provided, calculated as the proportion of subjects having a 
best response of CR or PR, respectively. 
9.8. 
Secondary Analyses 
9.8.1. 
Secondary Efficacy Analyses 
Secondary efficacy analyses will be performed based on IRC assessment and/or Investigator 
assessment of disease response as specified below. Consequently, endpoints using IRC 
assessments will be derived using only responses provided by IRC regardless of Investigator 
responses. Similarly, endpoints using Investigator assessments will be derived using only 
responses provided by Investigator regardless of IRC responses. The following secondary efficacy 
endpoints will be assessed according to the Lugano classification (Cheson 2014; 
): 
• DOR by IRC and Investigator 
• CRR by IRC and Investigator 
• ORR (CR + PR) by Investigator  
• PFS by IRC 
In addition, incidence of subjects receiving subsequent transplant and OS will be assessed. 
9.8.1.1. 
Duration of Response by IRC and Investigator 
The DOR defined as time from first assessment of PR or CR to the first assessment of progressive 
disease will be summarized by descriptive statistics including median DOR and respective 95% 
CIs and Kaplan-Meier estimates. DOR will also be listed.  
Subjects who started a new anti-lymphoma therapy prior to a documented progressive disease will 
be censored at the last disease assessment prior to initiation of new anti-lymphoma therapy. 
Detailed censoring rules will be described in the SAP. 


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9.8.1.2. 
CRR by IRC and Investigator 
The CRR will be calculated as the proportion of subjects having CR as best response. 
9.8.1.3. 
ORR by Investigator  
The primary analysis will be repeated using the local Investigator assessments.  
9.8.1.4. 
Progression-free Survival by IRC and Overall Survival 
Time from first treatment (acimtamig/AlloNK®) received until PFS/OS will be summarized by 
Kaplan-Meier estimates, median PFS/OS and respective 95% CIs. Subjects with no event will be 
censored at the last available disease assessment for PFS and at the last time point known alive for 
OS. A detailed censoring rule table will be presented in the SAP. 
9.8.1.5. 
Subsequent Transplant 
The incidence of subjects receiving subsequent transplant will be assessed and summarized by 
percentage rates and 95% CIs. 
Additional efficacy parameters may be defined in the SAP. 
9.8.2. 
Safety Analyses 
Treatment-emergent adverse events are those events with onset at/or after the first administration 
of any study drug of the regimen (acimtamig, AlloNK® or any study treatment such as 
lymphodepletion or IL-2) until 30 days after last administration of any study drug. TEAEs and 
SAEs will be coded using MedDRA and graded using NCI CTCAE v5.0 (including neurotoxicities 
that are not considered ICANS) except for CRS and ICANS, which will be graded according to 
the ASTCT grading, TLS will be graded according to the Cairo-Bishop TLS grading system and 
acute GVHD will be grading according to the Mount Sinai Acute GvHD International Consortium 
(MAGIC) criteria. 
Incidence, relatedness, and severity of TEAEs and SAEs will be tabulated and listed. Deaths within 
30 days after the last dose and the corresponding reasons will be summarized. Also, overall 
mortality will be summarized.  
Safety laboratory results will be graded by NCI CTCAE v5.0 if no grading exists values will be 
classified into low/normal/high based on laboratory normal ranges. All laboratory values will be 
listed. A separate listing for abnormal lab values (Grade 3 and higher, and low/high values) will 
be presented. 
Vital Signs will be summarized by descriptive statistics at each visit including change from 
baseline. All values will also be listed. 
9.8.3. 
Immunogenicity Analyses 
Immunogenicity parameters, including frequency of subjects developing ADAs against acimtamig 
or AlloNK®, will be summarized by descriptive statistics and listed for both acimtamig and 
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10. 
SAFETY MANAGEMENT 
10.1. 
Safety Definitions 
10.1.1. 
Adverse Event  
An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical 
condition in a subject or clinical investigation subject administered a medicinal product and which 
does not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (including a clinically significant abnormal laboratory finding, 
symptom, or disease temporally associated with the use of a medicinal (investigational) product or 
study procedure, whether assessed as related or unrelated. 
During clinical studies, AEs can be spontaneously reported or elicited during open-ended 
questioning, examination, or evaluation of a subject. To prevent reporting bias, subjects should not 
be questioned regarding the specific occurrence of one or more AEs. Adverse events include: 
• Worsening (change in nature, severity, or frequency) of conditions present at the start of 
the study; 
• Intercurrent illness; 
• Drug interactions; 
• Any safety events resulting from procedures required by the protocol. 
• Experiences related or possibly related to concomitant medications; 
• Clinically significant abnormal laboratory values or shifts from baseline;  
• Clinically significant abnormalities in physical examination, vital signs, weight, or ECG; 
and 
• An accident or injury.  
10.1.2. 
Special Considerations Related to AE Reporting 
The Investigator shall record in the eCRF all AEs, and special situations including Misuse, 
Medication error, Overdose (refer to Section 10.1.5) or a new cancer that is not a condition of the 
study, after the subject signs the ICF until 30 days after the last administration or before start of 
any new anti-cancer treatment whichever is sooner, regardless of causal relationship to the 
investigational medicinal product (IMP). 
The term “disease progression” alone should not be used when reporting AEs or SAEs. 
Additionally, death that occurs as consequence of disease progression is an outcome, and NOT an 
AE.  
Example, a subject died due to a pulmonary hemorrhage secondary to tumor progression; a SAE 
report with the event pulmonary hemorrhage should be notified as a Grade 5 (fatal).  
Surgical procedures or other therapeutic interventions themselves are not AEs, but the condition 
for which the surgery/intervention is required is an AE and should be documented accordingly. 


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Planned surgical measures and the condition(s) leading to these measures are not AEs, if the 
condition(s) was (were) known before the period of observation and did not worsen during study. 
In the latter case, the condition should be reported as medical history. 
Pregnancy is not considered an AE, although a subject will be withdrawn from the study if a 
pregnancy occurs (please refer to Section 5.4.2 for more details). The pregnancy must be reported 
as instructed in Section 10.3.2 and will be followed for at least 8 weeks after delivery. 
10.1.3. 
Adverse Events of Special Interest  
An AE of special interest (AESI) (serious or non-serious) is one of scientific and medical concern 
specific to the Sponsor’s product or program, for which ongoing monitoring and rapid 
communication by the Investigator to the Sponsor are necessary.  
In order to increase the understanding of infusion-related reaction (IRR) and CRS, these events are 
considered to be AESIs and must be reported by the Investigator within 24 hours as per the 
instructions outlined in Section 10.3.1. All symptoms suggesting an IRR or CRS should be 
mentioned in the report. Information related to the timely development of symptoms relative to 
dose per time, actions taken as well as outcome of events are of particular interest and shall be 
reported to the Sponsor or delegate for proper case evaluation. 
Infusion related reactions can manifest with allergic or anaphylactic symptoms, including but not 
limited to chills, flushing, hypotension, fever, hypoxia, loss of consciousness, bronchospasm and 
even with cardiac arrest. Although the majority of such IRRs are mild to moderate, in some rare 
cases these can be life threatening or even fatal. Most of the IRRs are associated with the first 
infusion (during or shortly after the infusion); however, IRRs can happen during or after any 
infusion, despite the lack of previous signs or symptoms. Infusion related reaction severity shall 
be graded using the classifications of NCI CTCAE v5.0 
Cytokine release syndrome occurring during or following infusion of study treatment can be 
further defined by symptoms such as fever, hypotension, and/or hypoxia as described in the 
ASTCT grading system. 
10.1.4. 
Serious Adverse Event  
An SAE is any AE, occurring at any dose and regardless of causality that is defined as any 
untoward medical occurrence that at any dose causes or qualifies as the following: 
• Fatal; 
• Results in death; 
• Life-threatening; “Life-threatening” means that the subject was at immediate risk of death 
at the time of the SAE; it does not refer to an SAE that hypothetically might have caused 
death if it were more severe. 
• Requires hospitalization or prolongation of existing hospitalization. – This means that 
hospital inpatient admission or prolongation of hospital stay were required for the treatment 
of the SAE or that they occurred as a consequence of the event. 
 
 


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Note :  
- 
Visits to a hospital by ambulance or to the emergency room without admission will not 
be regarded as hospitalization unless the event fulfills any other of the serious criteria. 
- 
Hospitalization for elective treatment or diagnostic procedure of a pre-existing 
condition that did not worsen from baseline (including study disease) is NOT 
considered an SAE.  
- 
Hospitalization and pre-planned admission to hospital for administration of 
chemotherapy, AlloNK®, IL-2 (if applicable), acimtamig, or other protocol-mandated 
procedures (i.e., lymphodepletion or biopsy) do NOT qualify as serious unless a new 
AE occurs that results in prolongation or meets any of the other “seriousness” criteria. 
• Results in persistent or significant disability or incapacity – “Persistent or significant 
disability or incapacity” means a permanent or significant and substantial disruption of a 
person’s ability to carry out normal life functions.  
• Is a congenital anomaly or birth defect; and/or 
• Is an important medical event – An important medical event is a serious event that may 
not be immediately life threatening or result in death, hospitalization, disability or 
incapacity but may jeopardize the subject or may require medical intervention to 
prevent one or more outcomes listed in the definition of serious. Examples of such events 
include potential drug induced liver injury (DILI), graft versus host disease (GVHD), 
multiple organ dysfunction syndrome, mucosal necrosis, intensive treatment (in an 
emergency room or at home) for allergic bronchospasm, convulsions that do not result in 
hospitalization, or the development of drug dependency or abuse, overdose or misuse. For 
more examples refer to the latest IME list released by EMA.For more examples refer to the 
latest IME list released by EMA. 
All SAEs will be followed until resolution, the condition stabilizes or is considered chronic, the 
event is otherwise explained, or the subject is lost to follow-up or withdraws consent. 
10.1.5. 
Overdose, Medication Error, and Misuse 
Overdose is defined as: >10% above the intended study drug daily dose is given or a dose interval 
<4 days between two consecutive doses. If the pharmacy discovers that an overdose has or may 
have been administered, they should contact the Investigator and Sponsor (or their delegate) 
immediately. 
Medication error is defined as: an unintended failure in the drug treatment process that leads to, or 
has the potential to lead to, harm to the subject. 
Misuse is defined as: situations where an investigational medicinal product is intentionally and 
inappropriately used not in accordance with the terms of the current protocol. 
10.2. 
Evaluation and Classification 
Following the subject’s written consent to participate in the study, all AEs will be collected. 
Pre-existing conditions that are detected prior to the subjects written consent will be recorded as 
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For all subjects, the AE reporting period will start with signing the informed consent form (ICF) 
for all AEs and continue until 30 days after the last dose study treatment (acimtamig and/or 
AlloNK®) or before initiation of subsequent anticancer therapies. (Note: any SAEs that occur prior 
to the first dose of lymphodepletion will still be reported according to the instructions provided on 
reporting of SAEs in Section 10.3.1). Where known, the diagnosis of the underlying illness or 
disorder should be recorded, rather than listing individual symptoms. 
The following Information should be captured for all AEs: date of onset and resolution, severity 
of the event, assessment as to whether the event was serious or non-serious, Investigator’s opinion 
of the relationship to study drug(s), treatment required for the AE, action taken with study drug(s), 
and information regarding resolution/outcome. 
10.2.1. 
Severity Assessment 
All AEs (including SAEs) are to be accurately recorded on the AE page of the subject’s eCRF. 
Each event will be graded for severity using the classifications of NCI CTCAE v5.0 (including 
neuro-toxicities that are not considered ICANS) except for CRS and ICANS, which will be graded 
according to the ASTCT grading (Table 4), TLS will be graded according to the Cairo-Bishop 
TLS grading system (Appendix H), and acute GVHD will be grading according to the MAGIC 
criteria (Table 5). For events not addressed in the NCI CTCAE v5.0, ASTCT grading 
classifications, the Cairo-Bishop TLS grading system, or MAGIC criteria, the following grading 
will apply: 
• Mild (Grade 1) – Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
• Moderate (Grade 2) – Moderate; minimal, local, or non-invasive intervention indicated; 
limiting age-appropriate instrumental activity of daily living. 
• Severe (Grade 3) – Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
activity of daily living. 
• Life-threatening (Grade 4) – Life-threatening consequences; urgent intervention indicated. 
• Fatal (Grade 5) – Related to AE. 
During initial dosing and its respective post-observation period, any clinical finding despite its 
severity that represents a change from baseline (e.g., mild skin reaction, fatigue, myalgia, etc.) 
should be recorded and followed until resolution. Likewise, any clinically significant finding 
identified during the remaining course of the study, which represents a change from baseline would 
be required to be recorded by the Investigator. 
10.2.2. 
Expectedness Assessment 
The Sponsor will assess all SAEs whether they are expected or unexpected. An unexpected AE is 
any adverse drug event, the outcome, specificity, or severity of which is not listed in the current 
Reference Safety Information (RSI) of the IB. 


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10.2.3. 
Causality Assessment 
All AEs (including SAEs) will be assessed by the Investigator and Sponsor for the causal 
relationship of the AE to the study drug(s) using the following definitions described in Table 8. 
For reporting and data analysis purposes, AEs reported with a causality assessment of “Definitely”, 
“Probably”, and “Possibly” are to be considered as “having a reasonable causal relationship” to 
study drug. In case of disagreement between the Investigator and the Sponsor, the more 
conservative assessment will determine the reportability of the case. 
Table 8: 
Relationship to Study Drug 
 
Relationship 
Description 
1 
Not related 
This category applies to those AEs which, after careful consideration, are clearly and 
incontrovertibly due to extraneous causes (disease, environment, etc.). 
2 
Unlikely 
(must have 2) 
In general, this category can be considered applicable to those AEs which, after careful 
medical consideration at the time they are evaluated, are judged to be unrelated to the 
test drug. An AE may be considered unlikely if or when: 
1. It does not follow a reasonable temporal sequence from administration of the test drug. 
2. It could readily have been produced by the subject’s clinical state, environmental or 
toxic factors, or other modes of therapy administered to the subject. 
3. It does not follow a known pattern of response to the test drug. 
4. It does not reappear or worsen when the drug is re-administered. 
3 
Possibly 
(must have 2) 
This category applies to those AEs for which, after careful medical consideration at the 
time they are evaluated, a connection with the test drug administration appears unlikely 
but cannot be ruled out with certainty. An AE may be considered possibly related if or 
when: 
1. It follows a reasonable temporal sequence from administration of the test drug. 
2. It could not readily have been produced by the subject’s clinical state, environmental 
or toxic factors, or other modes of therapy administered to the subject. 
3. It follows a known pattern of response to the test drug. 
4 
Probably 
(must have 3) 
This category applies to those AEs for which, after careful medical consideration at the 
time they are evaluated, are felt with a high degree of certainty to be related to the test 
drug. An AE may be considered probably related if or when: 
1. It follows a reasonable temporal sequence from administration of the test drug. 
2. It could not be reasonably explained by the known characteristics of the subject’s 
clinical state, environmental or toxic factors, or other modes of therapy administered to 
the subject. 
3. It disappears or decreases on cessation or reduction in dose. There are important 
exceptions when an AE does not disappear upon discontinuation of the drug, yet drug-
relatedness clearly exists (e.g., bone marrow depression, fixed drug eruptions, tardive 
dyskinesia). 
4. It follows a known pattern of response to the test drug. 
5 
Definitely 
(must have all) 
This category applies to those AEs which, the Investigator feels are incontrovertibly 
related to test drug. An AE may be assigned an attribution of definitely related if or when: 
1. It follows a reasonable temporal sequence from administration of the test drug. 
2. It could not be reasonably explained by the known characteristics of the subject’s 
clinical state, environmental or toxic factors, or other modes of therapy administered to 
the subject. 


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Relationship 
Description 
3. It disappears or decreases on cessation or reduction in dose with re-exposure to drug. 
(Note: this is not to be construed as requiring re-exposure of the subject, however, a 
category of definitely related can only be used when a recurrence is observed.)  
4. It follows a known pattern of response to the test drug. 
Abbreviations: AE = adverse event 
10.3. 
Safety Reporting 
Timely and complete reporting of safety information is very important to assist in the identification 
of any untoward medical occurrence, thereby ensuring: 
• The safety of study subjects; 
• A greater understanding of the overall safety profile of the investigational drug; 
• Recognition of any dose-related investigational drug toxicity; 
• Appropriate modification of study protocols; 
• Improvements in study design or procedures as required; and 
• Adherence to required ethical and regulatory requirements for clinical study conduct. 
10.3.1. 
Safety Reporting of Serious Adverse Events and Adverse Events of Special 
Interest  
Investigators must report SAEs/AESIs to the Sponsor or delegate within 24 hours of becoming 
aware of the event, by entering all required information into the Electronic Data Capture (EDC) 
system by completing an electronic Case Report Form (eCRF) in accordance with the eCRF 
completion guidelines.  
Upon completion of the eCRF and submission of the eCRF, an automated notification will be 
triggered to the sponsor (or delegate). The investigator will receive an acknowledgement of receipt 
within one business day of submitting the report. 
 
 
 
 
 
 
 
Other supporting documentation of the event may be requested by the Sponsor or delegate and 
should be provided as soon as possible in an anonymized manner. Follow-up information about a 
previously reported SAE/AESI must be reported within the same applicable timeframe of 
receiving it. Serious AEs/AESIs will be followed up until resolution or stabilization at a level 
acceptable to the Investigator and/or the Sponsor. 
The Investigator is not responsible for actively seeking new SAEs/AESIs after the safety follow-up 
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10.3.2. 
Exposure During Pregnancy or Lactation 
Although pregnancy and lactation are not considered AEs, they are considered an exclusion 
criterion for this study (Section 5.2). 
Any pregnancy or lactation in a subject, or pregnancy in a subject’s partner that occurs after the 
ICF is signed through 60 days following cessation of study drug treatment shall be recorded by the 
Investigator on the Pregnancy Form provided by the sponsor (or delegate) as soon as possible but 
no later than 14 days of being made aware of the pregnancy. 
 
Any events (including congenital anomalies/birth 
defects) that meet the definition of a SAE would need to be notified to the Sponsor as per 
Section 10.3.1. The Investigator must also ensure that any pregnancy is followed up until outcome, 
i.e., the health of the infant will be queried by the Sponsor or delegate. Parental and neonatal 
outcomes must be recorded even if they are completely normal and without AEs. Off-spring should 
be followed up for at least 8 weeks after delivery. Longer observation periods may be determined 
by the Sponsor or delegate if an adverse outcome of the pregnancy was observed.  
A congenital anomaly will only need to be expedited to competent authorities and ECs/IRBs if it 
meets the definition of a suspected unexpected serious adverse reaction (SUSAR). In addition, 
pregnancy case(s) will be reported as part of the annual Development Safety Update Report 
(DSUR). 
10.3.3. 
Other Reporting Obligations 
Special situations including misuse, medication error, overdose, or a new cancer that is not a 
condition of the study, shall be recorded in the eCRF. Those events shall be collected from the 
time the subject signs the ICF until 30 days after the last administration or before start of any new 
anti-cancer treatment whichever is sooner, regardless of causal relationship to the IMP.  
If the special situation results in an adverse event that meets any of the seriousness criterion defined 
in Section 10.1.4, the case qualifies for immediate reporting and has to be reported within 24 hours 
using the instructions for SAE reporting stated in Section 10.3.1. 
10.4. 
Follow-Up Information on Reported Events 
The Sponsor (or their delegate) will review SAE reports for missing information and send queries 
to the site for resolution as appropriate. 
An SAE is followed until it is considered resolved, returns to baseline, is chronically ongoing, 
stabilized, or is otherwise explained by the Investigator. 
Collection of complete information concerning reported events is extremely important. Thus, 
follow-up information that becomes available as the event evolves, as well as supporting 
documentation (e.g., hospital discharge summaries and autopsy reports), should be collected 
subsequently if not available at the time of the initial report and immediately uploaded to the eCRF.  


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Appropriate diagnostic tests should be performed and therapeutic measures, if indicated, should 
be instituted. Appropriate consultation and follow-up evaluations should be carried out by the 
Investigator (or designee).  
10.5. 
Reporting of Serious Adverse Events to Regulatory Authorities 
In accordance with the 21 CFR Part 312.32 and the International Council for Harmonization (ICH) 
Guidelines for Clinical Safety Data Management Definitions and Standards for Expedited 
Reporting, the Sponsor must submit written documentation in the form of an IND Safety Report 
or SUSAR reports, respectively. The Sponsor should submit to the regulatory authority all safety 
updates and periodic reports, as required by applicable regulatory requirements. The IND Safety 
Reports/SUSARs are required to be reported within 7 calendar days for fatal and life-threatening 
events and/or 15 calendar days for all other SUSARs. These timeframes begin with the date when 
the Sponsor or their delgate becomes aware of the IND Safety Reports/SUSARs. 
The Sponsor (or their delegate) will determine whether expedited reporting is necessary for SAEs 
depending on the assessment of seriousness, expectedness, and causal relationship. In case of 
disagreement between the Investigator and the Sponsor regarding causal relationship, the more 
conservative assessment will determine the reportability of the case. 
The Investigator must ensure they are aware and comply with any additional local reporting 
requirements. For all SAEs regardless of expectedness and causal relationship, the Sponsor (or 
their delegate) will assign a case number/ID to be used in all case-related correspondence regarding 
the event and can provide a MedWatch or Council for International Organizations of Medical 
Sciences (CIOMS I) form describing the event, for the Investigators to report to their local 
Institutional Review Board (IRB)/Ethics Committee (EC) or other committee. Other SAEs (e.g., 
expected or unrelated SAEs) should be reported per the relevant institution’s procedures (if 
required). 
Where required, submission of Safety Updates by the Investigator to local regulatory agencies 
should be handled according to local regulations. Otherwise, periodic safety reports to the 
regulatory agencies will be handled by the Sponsor (or their delegate). These safety updates will 
also include SAEs that do not require expedited reporting to the authorities. 
Periodically (at least annually), the IB will be updated to include new and relevant safety 
information. Expectedness assessment shall be based on the RSI section approved by regulatory 
agencies at the onset of the event. 
10.6. 
Study Interruption or Stopping Criteria for Safety Concerns 
Stopping rules for safety concerns include any of the following: 
1. Any Grade 5 TEAE at least possibly related to acimtamig and/or AlloNK® and clearly 
unrelated to either underlying HL/PTCL or disease progression.  
2. Any unexpected, significant or unacceptable risk to subjects as determined by the 
independent SRC 
3. Any Grade 3 or 4 TEAE at least possibly related to acimtamig and/or AlloNK® and 
clearly unrelated to either underlying HL/PTCL, disease progression occurring in ≥33% 


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of subjects with at least 6 subjects enrolled in the safety-run-in or ≥33% of subjects in 
the main study with the following exceptions: 
• ASTCT Grade 3 CRS or CTCAE Grade 3 IRR related toxicity that improve to 
Grade 2 or lower within 72 hours of adequate medical support 
• CTCAE Grade 3 fever, neutropenic fever, or infections that improve to Grade 2 or 
lower within 72 hours 
• CTCAE Grade 3 fatigue that improves to Grade 2 or lower within 10 days 
• CTCAE Grade 3 nausea, vomiting, or diarrhea that does not result in 
hospitalization, total parenteral nutrition, or tube feeding 
• CTCAE Grade 3 ALT, AST, alkaline phosphatase (ALP) (>5 × ULN) or bilirubin 
(>3 × ULN) resolving to Grade 1 or baseline within 7 days;  
• CTCAE Grade 3 electrolyte abnormalities that can be corrected with supportive 
therapy within 72 hours 
• CTCAE Grade 3 laboratory abnormality unless confirmed with a repeat test and 
considered clinically significant  
• QT interval with Fridericia’s correction (QTcF) prolongation (>500 msec or >60 
msec change from baseline) must be confirmed by 2 separate ECGs at least 6 hours 
apart or must be associated with arrhythmias in order to be considered a study 
interruption criterion 
If at least one of the stopping rules is met, subject recruitment will be paused and the safety data 
will be reviewed by the independent SRC (additional details will be provided in a separate charter). 
If the new safety findings are considered treatment related by the independent SRC, subjects who 
are already receiving study treatment and are deriving clinical benefit may continue study 
treatment at the discretion of the Investigator only after reconsenting a second informed consent 
that has been updated with the new safety information. 


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11. 
QUALITY, CONTROL, AND QUALITY ASSURANCE 
This study will be conducted under GCP and all applicable regulatory requirements. To ensure 
data accuracy, completeness, and compliance, the study center should have processes in place for 
data review and quality control. Sponsor (or delegate) may also conduct a quality assurance audit. 
11.1. 
Data Recording, Monitoring of the Study, and Regulatory Compliance 
The project manager, or their designee, will make an initiation site visit to each institution to review 
the protocol and its requirements with the Investigator(s), inspect the drug storage area, fully 
inform the Investigator of his/her responsibilities and the procedures for assuring adequate and 
correct documentation. During the initiation site visit, the eCRF and other pertinent study materials 
will be reviewed with the Investigator’s research staff. During the course of the study, the CRA 
will make regular site visits in order to review protocol compliance, examine CRFs and individual 
subject’s medical records, and assure that the study is being conducted according to pertinent 
regulatory requirements including ICH-GCP. Sites should ensure that source documentation is 
available to enable verification of all eCRF data entries. The review of medical records will be 
done in a manner to ensure that subject confidentiality is maintained. 
All data will be collected using an eCRF within a fully validated and 21 CFR Part 11 compliant 
EDC system. All data will be entered into the eCRF by the site staff. These data will then be 
source-data verified and reviewed by the CRAs before data cleaning by data management is 
performed. All queries will be raised and resolved within the EDC system. During entry, 
programmatic checking of the data will be performed, and, once saved into the database, more 
complex programmatic checks will also be performed. During the conduct of the study, all system 
users will have real-time access to the data. The level of access to the data and study privileges 
will be determined by their user role. 
After all queries have been resolved, the SAP approved and signed, and any summary/analysis 
populations approved, the database will be locked, and the data released for summary and analysis. 
All summary and analysis of the data will be performed using appropriate versions of SAS® and 
WinNonLin Pro, or equivalent. 
11.2. 
Study Monitoring 
Clinical Research Associates will be responsible for the monitoring of the study. The CRA will 
review the progress of the study on a regular basis to ensure adequate and accurate data collection. 
Monitoring site visits to review the eCRF, subject case notes, administrative documentation 
including the Investigator Site File, and frequent telephone/e-mail communications with site will 
be performed throughout the study. 
At each study monitoring visit, the Investigator will make available all records pertaining to the 
study. To allow sufficient time to assemble documentation for the CRA, monitoring visits will be 
confirmed in advance of planned visits. 
The process for study monitoring and source data verification requirements for the study will be 
specified in the Monitoring Plan (or equivalent). 


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11.3. 
Clinical Study Audit 
The Sponsor, Sponsor representative, or external regulatory agency may at any time during or after 
completion of the study conduct a GCP audit. Prior notice will be given to each site selected for 
audit in advance of a planned audit. 
11.4. 
Clinical Study Report 
The results of the study will be presented in a Clinical Study Report according to ICH guidelines. 
The CSR will be written once all enrolled cohorts reached the primary endpoint assessment. 
In case subjects are still being treated with study medication at the final data cut-off date for this 
study, such subjects will be kept on treatment in the study and data collected will then be reported 
in an addendum to the final CSR. It will be noted in the final CSR that such a revised report may 
be provided. 
11.5. 
Data Availability 
The Investigator is required to maintain copies of all essential study documentation, including the 
Site Study File, all eCRF data (including the full audit trail and all data queries), signed ICFs, and 
records for the receipt and disposition of study drug. 
During the study, the Investigator must make study data accessible to the CRA, the Sponsor (or a 
third-party auditor assigned by the Sponsor), and relevant IRB/EC and regulatory agencies. A file 
(or appropriate records) for each subject must be maintained that includes the signed ICF and all 
source documentation related to that subject. The Investigator must ensure the availability of 
source documents from which the information in the eCRF was derived. 
Please refer to Section 13.2 for details of required record retention for the study. 
11.6. 
Curricula Vitae and Financial Disclosure of Investigators  
All Principal Investigators will be required to provide a current signed and dated curriculum vitae, 
a completed FDA Form 1572 (or accepted equivalent), and a financial disclosure statement. All 
Sub-investigators will be required to provide a current curriculum vitae and a financial disclosure 
statement. 
11.7. 
Protocol Modifications 
No modification of the protocol should be implemented without the prior written approval of the 
Sponsor. Any such changes which may affect a subject’s treatment or informed consent, especially 
those increasing potential risks, must receive prior approval by the IRB/EC. The exception to this 
is where modifications are necessary to eliminate an immediate hazard to study subjects, or when 
the change involves only logistical or administrative aspects of the study (e.g., change in monitor, 
change in telephone number, typos). Other administrative revisions which may impact the clinical 
portion of a study will be duly reported to the IRB/EC by the Principal Investigator. 
11.8. 
Study or Site Termination 
If the Sponsor or their representatives, Investigator, or Competent Authority discover conditions 
during the study that indicate that the study or site involvement should be terminated, this action 


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may be taken after appropriate consultation with the Sponsor and the Investigator. Conditions that 
may warrant termination of the study or a study site include, but are not limited to: 
• 
The discovery of an unexpected, serious, or unacceptable risk to subjects enrolled 
in the study; 
• 
The decision on the part of the Sponsor to suspend or discontinue testing, 
evaluation, or development of the study drug; 
• 
Failure of an Investigator(s) to comply with pertinent clinical study regulations; 
• 
Submission of knowingly false information from the study site to the Sponsor, 
CRA, or Competent Authority; and 
• 
Insufficient adherence to protocol requirements. 
Study termination and/or site close out will be performed in accordance with applicable local 
regulations. 
 
 


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12. 
ETHICAL CONSIDERATIONS 
The Investigator will obtain written informed consent from each subject, or their authorized 
representative, participating in the study. The form must be signed, witnessed and dated. The ICF 
will contain all the Essential Elements of Informed Consent set forth in 21 CFR Part 50, the ICH 
Guideline for GCP, and the terms of the Declaration of Helsinki. Copies of the signed document 
should be given to the subject and filed in the Investigator’s Study File, as well as the subject’s 
medical record if in conformance with the institution’s Standard Operating Procedures. 
The final study protocol and subject ICF will be approved by the appropriate IRB/EC for each 
investigational site. Approval will be received in writing before initiation of the study. 
Changes to the protocol during the study will be documented as amendments. Depending on the 
contents of the amendments and local legal requirements, the amendment will be submitted for 
approval to the relevant IRB/EC and to the relevant competent authorities prior to implementation. 
Exceptions are cases of changes made to protect subject safety, which will be implemented 
immediately. 
If an amendment substantially alters the study design, increases the potential risk to the subjects, 
affects the treatment of the subject, or might otherwise influence the willingness of the subject to 
participate in the study, then the ICF must be revised and submitted to the relevant IRB/EC and, 
where necessary, to the relevant competent authorities, for review and approval. When a subject 
is currently undergoing study procedures and is affected by the amendment, then the subject must 
be asked to consent again using the new ICF. 
12.1. 
Ethical Conduct of the Study 
The study will be conducted in accordance with ICH GCP, the Declaration of Helsinki, the Clinical 
trials – Regulation EU No 536/2014, the GCP Directive 2005/28/EC, the requirements of local 
IRBs/ECs, and the 21 CFR Part 50. 
12.2. 
Informed Consent 
The principles of informed consent in the Declaration of Helsinki and GCP guidelines will be 
implemented before any protocol-specific procedures or interventions are carried out. 
All subjects will be informed that participation is voluntary and that they can cease participation 
at any time without necessarily giving a reason and without any penalty or loss of benefits to which 
they are entitled. 
With the help of the ICF, the subject will be informed about the study treatments and anticipated 
effects and the reason, design, and implication of the study. The subject must give consent to 
participate prior to enrollment in the study. This consent must be given in writing. The Investigator 
who conducts the informed consent discussion must also sign. The Investigator may delegate this 
responsibility to a suitably qualified member of the study team (e.g., Sub-Investigator) if permitted 
by local regulations. This delegation of responsibility must be recorded in the Study File. By giving 
signed consent, the subject will confirm that his or her participation is voluntary and that he or she 
will follow the instructions of the Investigator and answer the questions asked. Signatures must be 
personally dated. 


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The signed and dated consent form will be kept by the Investigator. Prior to participation in the 
study, the subject should receive a copy of the signed and dated written ICF. 
The ICF must include all elements required by law, local regulations, GCP and ICH guidelines 
including consent to allow the Sponsor, Sponsor representative, or external regulatory auditor to 
review the subject’s medical records. This gives permission to examine, analyze, verify, and 
reproduce any records and reports that are important to the evaluation of the study. 
Any party with direct access must take all reasonable precautions within the constraints of the 
applicable regulatory requirement(s) to maintain the confidentiality of the subjects’ identities and 
Sponsor’s proprietary information. It is the CRA’s responsibility to verify that each subject has 
consented, in writing, to direct access. 
12.3. 
Subject Participation Card 
A study participation card will be provided to subjects where required by local regulations or 
IRB/EC. The card will indicate that he or she is participating in a clinical study and give the 
name and contact details of the Sponsor and the Investigator/study site. The subject will be asked 
to retain this card while participating in the study and show it to any other medical practitioners 
consulted during this time. Subjects will be advised to contact the Investigator/study site if there 
are any questions.  
12.4. 
Insurance 
Appropriate insurance for this study will be arranged by Affimed (or their delegate), as Sponsor 
of the clinical study, in accordance with the regulatory requirements of the countries involved. A 
copy of the country-specific insurance certificate will be held in the Trial Master File (TMF) and 
in the Investigator Site File. 
12.5. 
Institutional Review Board/Independent Ethics Committee 
The study will not be initiated without the approval of the IRB/EC and compliance with all 
administrative requirements of the governing body of the institution. This protocol, consent 
procedures, and any amendments must be approved by the IRB/EC in compliance with current 
regulations of the FDA and the European Union as applicable and in accordance with ICH GCPs. 
A letter of approval will be sent to the Sponsor prior to initiation of the study and when any 
subsequent modifications are made. The IRB/EC will be kept informed by the Investigator, 
contract research organization or the Sponsor, as required by national regulations, as to the 
progress of the study as well as to any serious and unexpected adverse events. 
12.6. 
Subject Privacy 
The Investigator must ensure that subject privacy is maintained. On the eCRF or other documents 
submitted to the Sponsor, subjects will be identified by a subject number only. Clinical study 
documents that are not submitted to the Sponsor (e.g., signed ICF) should be kept in a confidential 
file by the Principal Investigator. 
In accordance with local, national, or federal regulations, the Investigator will allow the Sponsor 
or their designee personnel access to all pertinent medical records to verify the data gathered on 
the CRFs and to audit the data collection process. Regulatory agencies such as the FDA may also 


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request access to all study records, including source documentation for inspection. Clinical 
information will not be released without the written permission of the subject as outlined in the 
subject consent form. 
 
 


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13. 
DATA HANDLING AND RECORDKEEPING 
13.1. 
Recording of Data 
The Investigator will be responsible for the recording of all data on the CRFs provided, as certified 
by the Investigator’s signature and date on the designated pages. Should any value be significantly 
different from normal, the Investigator will comment in the appropriate sections provided in the 
CRFs. 
The Investigator will provide access to his/her original records to permit a representative from the 
Sponsor to verify the proper transcription of data. To facilitate photocopying, entries must be 
recorded legibly in black ink only. Erroneous entries will be crossed out with a single line, so as 
to remain legible. The correct value will be entered above the error and then initialed and dated by 
the person authorized to make the correction. 
13.2. 
Study Record Retention 
All clinical study documents must be retained by the Investigator until at least 2 years or according 
to local laws, whichever is longer, after the last approval of a marketing application in an ICH 
region (i.e., US, Europe, or Japan) and until there are no pending or planned marketing applications 
in an ICH region. If no application is filed or if the application is not approved for such indication, 
the Investigator must retain all clinical study documents until 2 years after the investigation is 
discontinued and regulatory authorities have been notified. Investigators may be required to retain 
documents longer if specified by regulatory requirements, or by local regulations. 
Subjects’ medical files should be retained in accordance with applicable legislation and with the 
maximum period permitted by the hospital, institution, or private practice. 


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Research; 2021 April 8-13; New Orleans LA. Philadelphia (PA): AACR; 2022. Abstract 
Nr  CT003.  
Nieto Y, Banerjee P, Kaur I et al. Innate Cell Engager (ICE®) AFM13 Combined with Preactivated 
and Expanded Cord Blood (CB)-Derived natural killer (NK) Cells for Patients (Pts) with 
Refractory CD30-Positive Hodgkin (HL) or Non-Hodgkin Lymphomas (NHL). American Society 
of Hematology 2022  
Nieto Y., et al., Innate Cell Engager (ICE®) AFM13 Combined with Preactivated and Expanded 
(P+E) Cord Blood (CB)-Derived Natural Killer (NK) Cells for Patients with Refractory CD30-
Positive Lymphomas: Final Results, Blood, Volume 142, Supplement 1, 2023, Page 774, ISSN 
0006-4971, https://doi.org/10.1182/blood-2023-172980. 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655. 
Ramos CA, Grover NS, Beaven AW, et al. Anti-CD30 CAR-T Cell Therapy in Relapsed and 
Refractory 
Hodgkin 
Lymphoma. J 
Clin 
Oncol. 
2020;38(32):3794-3804. 
Doi:10.1200/JCO.20.01342. 
Reagan PM, Friedberg JW. Axicabtagene ciloleucel and brexucabtagene autoleucel in relapsed 
and refractory diffuse large B-cell and mantle cell lymphomas. Future Oncol. 2021 ;17(11) :1269-
1283. Doi :10.2217/fon-2020-0291. 
Reiners KS, Kessler J, Sauer M, et al. Rescue of impaired NK cell activity in Hodgkin lymphoma 
with bispecific antibodies in vitro and in patients. Mol 2018-1092, Version 13.0 19 January 2022 
Page 47 of 47 Ther 2013;21:895-903. 
Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in 
mismatched hematopoietic transplants. Science. 2002 Mar 15;295(5562):2097-100.  
Shi J, Tricot G, Szmania S, et al. Infusion of haplo-identical killer immunoglobulin-like receptor 
ligand mismatched NK cells for relapsed myeloma in the setting of autologous stem cell 
transplantation. Br J Haematol. 2008 Dec;143(5):641-53.  
Shimasaki N, Jain A, Campana D. NK cells for cancer immunotherapy. Nature Reviews Drug 
Discovery. 2020 Jan; 19: 200-218.  
Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 
Mar;10(1):1-10.  
Suen WC, Lee WY, Leung KT, et al. Natural Killer Cell-Based Cancer Immunotherapy: A Review 
on 10 Years Completed Clinical Trials. Cancer Invest. 2018 ;36(8) :431-457.  
Szmania S, Lapteva N, Garg T, et al. Ex vivo-expanded natural killer cells demonstrate robust 
proliferation in vivo in high-risk relapsed multiple myeloma patients. J Immunother. 2015 
Jan;38(1):24-36.  
Voorhees TJ, Beaven AW. Therapeutic Updates for Relapsed and Refractory Classical Hodgkin 
Lymphoma. 
Cancers 
(Basel). 
2020;12(10):2887. 
Published 
2020 
Oct 
8. 
Doi:10.3390/cancers12102887. 


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Yang Y, Lim O, Kim TM, et al. Phase I study of random healthy donor–derived allogeneic natural 
killer cell therapy in patients with malignant lymphoma or advanced solid tumors. Cancer 
immunology research. 2016 Mar 1;4(3):215-24. 






















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APPENDIX E. CONTRACEPTIVE GUIDANCE 
Section E.1.  
Female Participants 
Females of childbearing potential must agree to sexual abstinence (defined below) or be willing to 
use a highly effective method of contraception for the course of the study from 14 days prior to 
the first dose of lymphodepletion through 120 days after the last dose of study drug (acimtamig 
and/or AlloNK®). Acceptable highly effective birth control methods include: 
• Oral, intravaginal, or transdermal combined (estrogen and progestogen containing) 
hormonal contraception associated with inhibition of ovulation;  
• Oral, injectable, or implantable progestogen-only hormonal contraception associated 
with inhibition of ovulation;  
• Intrauterine device;  
• Intrauterine hormone-releasing system;  
• Bilateral tubal occlusion;  
• Vasectomized partner (provided that partner is the sole sexual partner of the female of 
reproductive potential and that the vasectomized partner has received medical 
assessment of the surgical success); and  
• Sexual abstinence. 
In the context of this study, sexual abstinence is considered a highly effective method 
only if defined as refraining from heterosexual intercourse from 14 days prior to the 
first dose of lymphodepletion up to 120 days after the last dose of study drug 
(acimtamig and/or AlloNK®). The reliability of sexual abstinence needs to be evaluated 
in relation to the duration of the clinical study and the preferred and usual lifestyle of 
the subject. 
Section E.2.  
Male Participants 
Male subjects are eligible to participate if they agree to the following, starting with the first dose 
of lymphodepletion through 120 days after the last dose of study drug (acimtamig and/or AlloNK®) 
• Refrain from donating sperm 
AND 
• Female partners must agree to use contraception/barrier as detailed below 
Section E.3.  
Collection of Pregnancy Information 
Male subjects with partners who become pregnant: 
• The Investigator will attempt to collect pregnancy information on any male subject’s 
female partner who becomes pregnant while the male subject is in this study. 
• After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the Investigator will record pregnancy information on the appropriate 
form and submit it to the Sponsor within 24 hours of learning of the partner’s 
pregnancy. The female partner will also be followed to determine the outcome of the 
pregnancy. Information on the status of the mother and child will be forwarded to the 


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Sponsor. Generally, the follow-up will be at least 8 weeks following the delivery. Any 
termination of the pregnancy will be reported regardless of fetal status (presence or 
absence of anomalies) or indication for the procedure. 


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APPENDIX H. CAIRO-BISHOP DEFINITION AND GRADING OF 
TUMOR LYSIS SYNDROME 
Table 14: Cairo-Bishop Definition of Laboratory Tumor Lysis Syndrome 
Uric acid 
x ≥ 476 µmol/L or 25% increase from baseline 
Potassium 
x ≥ 6.0 mmol/L or 25% increase from baseline 
Phosphorous 
x ≥ 1.45 mmol/L or 25% increase from baseline   
Calcium 
x ≤ 1.75 mmol/L or 25% decrease from baseline 
Source: Cairo and Bishop 2004 
 
Table 15: 
Cairo-Bishop Definition of Clinical Tumor Lysis Syndrome 
(1) Creatine: x ≥ 1.5 ULN (age >12 years or age adjusted) 
(2) Cardiac arrhythmia/sudden death 
(3) Seizure 
Source: Cairo and Bishop 2004 
 
 
 
 
 


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Table 16: 
Cairo-Bishop Grading Classification of Tumor Lysis Syndrome 
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
LTLS 
–  
+ 
+ 
+ 
+ 
+ 
Creatinine 
≤ 1.5 × ULN 
1.5 × ULN 
> 1.5 × ULN 
> 3.0 – 6.0 × ULN 
> 6.0 × ULN 
Death 
Cardiac 
Arrhythmia 
None 
Intervention not 
indicated 
Non-urgent 
medical 
intervention 
indicated 
Symptomatic and 
incompletely 
controlled 
medically or 
controlled with 
device (e.g., 
defibrillator) 
Life-threatening 
(e.g., arrythmia 
associated with 
CHF, hypotension, 
syncope, shock) 
Death 
Seizure 
None 
- 
One brief 
generalized 
seizure; seizure(s) 
well controlled by 
anti-convulsant(s) 
or infrequent focal 
motor seizures not 
interfering with 
ADL 
Seizure in which 
consciousness is 
altered; poorly 
controlled seizure 
disorder; with 
breakthrough 
generalized 
seizures despite 
medical 
intervention 
Seizure of any kind 
which are 
prolonged, 
repetitive, or 
difficult to control 
(e.g., status 
epilepticus, 
intractable 
epilepsy) 
Death 
Notes: Clinical tumor lysis syndrome (CTLS) requires one or more clinical manifestations (Table 14) along with criteria for laboratory tumor lysis syndrome 
(LTLS) (Table 15). 
Maximal CTLS manifestation (renal, cardiac, neuro) defines the grade. 
Source: Cairo and Bishop 2004 
 
 
 
 
 
 
 

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Statistical Analysis Plan template version 1.0 dated 29-Oct-2020
STATISTICAL ANALYSIS PLAN
PROTOCOL AFM13-203
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 CD30-Positive Peripheral T-Cell 
Lymphoma (LuminICE-203)
Protocol code: 
AFM13-203
SAP Version: 
Final 2.0
SAP Date: 
20-SEP-2024
Author: 






Statistical Analysis Plan: AFM13-203
Review Status: Final
Version: 2.0
Version Date: 20-SEP-2024
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Statistical Analysis Plan template version 1.0 dated 29-Oct-2020
APPROVAL SIGNATURES
STUDY 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 CD30-Positive Peripheral T-Cell 
Lymphoma (LuminICE-203)
PROTOCOL NUMBER: AFM13-203
SAP Final 2.0, 20-SEP-2024
PSI
Signature:
................................................................
Date:
......................
Signature:
........... ....................................................
Date:
......................
Signature:
................................................................
Date:
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Signature:
........... ....................................................
Date:
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Affimed GmbH
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Date:
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Date:
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Statistical Analysis Plan: AFM13-203 
Review Status: Final 
 
Version: 2.0 
 
Version Date: 20-SEP-2024 
 
 
 
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Statistical Analysis Plan template version 1.0 dated 29-Oct-2020 
 
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS .......................................................................................................................................... 6 
1. 
INTRODUCTION ............................................................................................................................................. 8 
2. 
STUDY OBJECTIVES ...................................................................................................................................... 8 
2.1 
Primary Objectives ................................................................................................................................ 8 
2.2 
Secondary Objectives............................................................................................................................. 8 
2.3 
Exploratory Objectives ........................................................................................................................... 8 
3. 
STUDY DESCRIPTION .................................................................................................................................... 8 
4. 
SAMPLE SIZE AND POWER CALCULATION .................................................................................................... 8 
5. 
ANALYSIS ENDPOINTS .................................................................................................................................. 9 
5.1 
Primary Endpoint and Estimand............................................................................................................... 9 
5.2 
Secondary Endpoints ............................................................................................................................. 9 
5.3 
Exploratory Endpoints ........................................................................................................................... 10 
6. 
ANALYSIS POPULATIONS ............................................................................................................................ 10 
7. 
ANALYTICAL PLAN AND STATISTICAL METHODS ........................................................................................ 11 
7.1 
General Conventions and Statistical Considerations ................................................................................... 11 
7.2 
Definition of Baseline, Study Visits, and Visit Windows .............................................................................. 12 
7.3 
Handling of Missing Data ....................................................................................................................... 12 
7.4 
Protocol Deviations ............................................................................................................................... 12 
7.5 
Participant Disposition........................................................................................................................... 13 
7.6 
Participant Characteristics ..................................................................................................................... 13 
7.6.1 
Baseline and Demographic Characteristics ......................................................................................... 13 
7.6.2 
Medical History and Current Medical Conditions ................................................................................. 13 
7.6.3 
Prior and Concomitant Medication ....................................................................................................... 14 
7.7 
Efficacy Endpoints and Analysis .............................................................................................................. 14 
7.7.1 
Analysis of Primary Efficacy Endpoint .................................................................................................. 14 
7.7.2 
Analysis of Secondary Efficacy Endpoints ........................................................................................... 16 
7.7.3 
Analysis of Exploratory Endpoints ........................................................................................................ 19 
7.7.4 
Sensitivity Analysis ................................................................................................................................ 19 
7.8 
Safety Endpoints and Analysis ................................................................................................................ 20 
7.8.1 
Exposure to Study Treatment ............................................................................................................... 20 
7.8.2 
Adverse Events ..................................................................................................................................... 21 
7.8.3 
Laboratory Data ..................................................................................................................................... 22 
7.8.4 
ECG, Vital Signs, Physical Examination and ECOG Status ................................................................ 22 
7.8.5 
Cytokines ............................................................................................................................................... 22 
7.9 
Other Endpoints and Analysis................................................................................................................. 23 
7.9.1 
Subgroup Analysis ................................................................................................................................ 23 
8. 
INTERIM ANALYSIS ...................................................................................................................................... 23 
8.1 
Risk-Benefit Analysis of Safety Run In Period ........................................................................................... 23 
8.2 
Interim Analysis After 1st Stage of Simon’s Design Part.............................................................................. 24 
8.3 
Primary Analysis ................................................................................................................................... 25 
9. 
FINAL ANALYSIS ......................................................................................................................................... 25 
10. 
INDEPENDENT SAFETY REVIEW COMMITTEE (SRC)..................................................................................... 25 
11. 
DEVIATIONS FROM ANALYSIS AS DESCRIBED IN THE PROTOCOL .............................................................. 25 
12. 
PROGRAMMING SPECIFICATIONS ............................................................................................................... 26 
13. 
REFERENCES .............................................................................................................................................. 26 
 


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LIST OF ABBREVIATIONS 
 
ADA 
Anti-drug antibody 
AE 
Adverse event 
AESI 
Adverse events of special interest 
ASTCT 
American Society for Transplantation and Cellular Therapy 
ATC 
Anatomical Therapeutic Chemical (classification system) 
CI 
Confidence interval 
CR  
Complete response/remission 
CRR  
Complete response rate 
CRS 
Cytokine release syndrome 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Coefficient of variation 
DCR 
Disease control rate 
DOR  
Duration of response 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EORTC 
European Organisation for Research and Treatment of Cancer 
FAS 
Full analysis set 
HL 
Hodgkin lymphoma 
IA 
Interim analysis 
ICANS 
Immune effector cell-associated neurotoxicity syndrome 
IL-2 
Interleukin-2  
IRC  
Independent Radiology Committee 
ITT 
Intention-to-treat 
LTEAE 
Lymphodepletion-TEAEs 
MAGIC 
Mount Sinai Acute GvHD International Consortium 
Max 
Maximum 
MedDRA 
Medical Dictionary of Regulatory Activities 
mFAS 
Modified full analysis set 
Min 
Minimum 
MRD 
Measurable residual disease 
NCI 
National Cancer Institute 
NK 
Natural killer 
oFAS 
Overall full analysis set 
ORR 
Objective response rate 
OS 
Overall survival 
PET-CT  
Positron emission tomography-computed tomography 
PFS 
Progression-free survival  
PK 
Pharmacokinetic(s) 
PPS 
Per-protocol set 
PR  
Partial response 
PRR 
Partial responses rate 
PRO 
Patient-reported outcome 
PT 
Preferred term 
PTCL 
Peripheral T-cell lymphoma 
QoL 
Quality of Life 
R/R 
Refractory/relapsed 


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Statistical Analysis Plan template version 1.0 dated 29-Oct-2020 
 
SAE 
Serious adverse event 
SAS 
Safety analysis set 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
SOC 
System organ class 
SRC 
Safety Review Committee 
SRI 
Safety run-in set 
TEAE 
Treatment emergent adverse event 
TFL 
Tables, figures, listings 
TLS 
Tumor lysis syndrome 
WHO 
World Health Organization 
 
 








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cohorts of the study except for Cohort 6 (in run-in phase, Stage 1, and Stage 2) who 
received at least 1 dose of both acimtamig and AlloNK®. The oFAS will be used for 
sensitivity analyses of the primary endpoint. The exploratory cohorts are not included in 
oFAS because the results would be identical with those from the FAS analyses. 
x 
Safety run-in set (SRI): The SRI consists of all participants of the 4 safety run-in cohorts 
who received at least 66% of the acimtamig and AlloNK® combination during Cycle 1. The 
SRI will be used for the analysis of run-in phase data.  
x 
Acimtamig PK set: The acimtamig PK set consists of all participants (except those from 
Cohort 6) who have received at least 1 dose of acimtamig and have at least 1 post dose 
acimtamig PK measurement. 
x 
AlloNK PK set: The AlloNK PK set consists of all participants who have received at least 
1 dose of AlloNK® drug and have at least 1 post dose AlloNK® PK measurement. 
Participants who were screened and signed the informed consent but did not receive any 
treatment will be listed, including the reason for screen failure and any SAE that is related to a 
study procedure. These participants will not be part of any summary table except for summarizing 
disposition. 
 
7. 
ANALYTICAL PLAN AND STATISTICAL METHODS 
7.1 
GENERAL CONVENTIONS AND STATISTICAL CONSIDERATIONS 
Continuous variables will be summarized with the following statistics: number of non-missing 
observations, number of missing observations, mean, standard deviation (SD), median, 
1st quartile, 3rd quartile, minimum (min), and maximum (max). Moreover, geometric mean, 
coefficient of variation (CV), and geometric CV will be calculated for certain PK parameters.  
Categorical variables will be summarized using frequency table with counts for all categories 
including missing, and percentages for all non-missing category, calculated with the total number 
of non-missing values as denominator.  
Percentages for categorical data summaries will be displayed with 1 decimal point (e.g. 51.4%), 
except for 100% which will be presented with no decimals (i.e. 100%). Unless otherwise specified, 
percentages for baseline summaries will be based on the total number of participants in the 
analysis set, percentages for post-baseline summaries will be based on the total number of 
participants with non-missing values. 
Use of decimal places in descriptive statistics:  
x 
Min, Max: same as the actual data 
x 
Mean, Median, Q1, Q3: actual data + 1 decimal 
x 
SD: actual data + 2 decimals 
A maximum of 3 significant digits will be displayed. 
Analysis will be presented by cohort. Moreover, all HL cohorts (except Cohort 6) pooled will be 
analyzed (2 pooled cohorts for FAS, 4 pooled cohorts for oFAS and SAS).  




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7.5 
PARTICIPANT DISPOSITION 
The disposition summaries of participants will include: 
x 
Number of participants screened, number and percentage of screening failures with 
reasons for screening failure; percentages will be calculated from all screened 
participants. 
For all enrolled participants, the following will be presented for each cohort, and moreover 
separately in each cohort for participants who received and who did not receive IL-2 (percentages 
will be calculated from all enrolled participants in each cohort / from all participants who received 
and who did not receive IL-2 in each cohort): 
x 
Number and percentage of participants enrolled, overall and by site 
x 
Number and percentage of participants in the analysis sets 
x 
Number and percentage of participants discontinued treatment (with reason for treatment 
discontinuation) 
For all participants in FAS, the following will be presented (percentages will be calculated from all 
participants in FAS): 
x 
Number and percentage of participants continued and not continued into follow-up period 
x 
Reason for end of study for participants, with number and percentage of participants  
x 
Number and percentage of participants in each treatment cycle 
Inclusion and exclusion criteria violations and enrollment will be presented for all screened 
participants in data listings. The disposition listing will be created for all enrolled participants. 
7.6 
PARTICIPANT CHARACTERISTICS 
7.6.1 
BASELINE AND DEMOGRAPHIC CHARACTERISTICS 
The following characteristics will be summarized by treatment arms in FAS: 
x 
Demography: age at screening, sex, ethnicity, race 
x 
Vital signs: height, weight, temperature, respiratory rate, heart rate, systolic and diastolic 
blood pressure, overall vital signs assessment,  
x 
Physical examination result 
x 
Childbearing potential 
Listings of demography and baseline characteristics data will be created. 
7.6.2 
MEDICAL HISTORY AND CURRENT MEDICAL CONDITIONS 
The following will be summarized in FAS, and also listed: 
x 
The lymphoma history: 
o Subtype, time since initial cytological/histological diagnosis until screening 
o Stage and B-symptoms presence at initial diagnosis and at screening 


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o For 
HL 
cohorts: 
Classical 
HL-specific 
prognostic 
factors 
(erythrocyte 
sedimentation rate, lymph node involvement, Extranodal disease sites) at initial 
diagnosis and at screening, International Prognostic Score for HL at initial 
diagnosis, soluble CD30 result at screening 
o For PTCL cohort: Non-Hodgkin Lymphoma-specific prognostic factors (extranodal 
disease sites) at initial diagnosis and at screening, International Prognostic Index 
at initial diagnosis, local CD30 result (%) and soluble CD30 result 
x 
Medical history other than lymphoma 
x 
Prior anti-cancer therapies and surgeries (number of prior therapies, therapeutic agents, 
prior stem cell transplant, PD1 Inhibitor therapy, Brentuximab Vedotin (BV) therapy, Car-T 
therapy and radiotherapy, best response to the last line prior to the study start)  
Prior anti-cancer therapies will be coded by World Health Organization (WHO) Anatomical, 
Therapeutic, and Chemical (ATC) terms, summarized and listed.  
Medical history will be coded utilizing corresponding Medical Dictionary for Regulatory Activities 
(MedDRA; version 26 or later), summarized by System Organ Classes (SOCs) and Preferred 
Terms (PTs) and listed. 
7.6.3 
PRIOR AND CONCOMITANT MEDICATION 
Medication will be coded by World Health Organization (WHO) Anatomical, Therapeutic, and 
Chemical (ATC) terms (version March 2023 or later). All prior (ended before the first day of any 
study treatment, including lymphodepletion) and concomitant (started on or after the first day of 
study treatment or ongoing on that day) medications will be summarized by ATC level 2 term and 
PT for FAS. Where start and end dates are partially available, imputation will be done as outlined 
in Section 7.3. If start and end dates are completely missing or classifications cannot be 
conclusively made based on the available information, such treatments will be classified as 
concomitant medications. 
Prior and concomitant medications will be also presented in data listings. 
 
7.7 
EFFICACY ENDPOINTS AND ANALYSIS 
The endpoints by IRC assessments will be derived using only responses provided by IRC 
regardless of Investigator responses. Similarly, endpoints by Investigator assessments will be 
derived using only responses provided by Investigator regardless of IRC responses. All cohorts 
will be analyzed independently. 
All the efficacy endpoints values and original variables used for their evaluation will be listed; the 
subgroups (as defined in Section 7.9.1) will be included in the primary endpoint listing. 
7.7.1 
ANALYSIS OF PRIMARY EFFICACY ENDPOINT 
7.7.1.1 
ENDPOINT DESCRIPTION 
The primary endpoint is based on the ORR, calculated as the proportion of participants with 
having a best response of CR or PR as assessed by IRC according to the Lugano classification. 
A participant will be assumed as a responder if he/she achieves complete or partial response at 
any postbaseline visit; otherwise, he/she will be a non-responder. Participants with missing post-
baseline response will be classified as non-responders. 














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The summaries for exposure to study treatment will be presented for acimtamig, AlloNK® and 
lymphodepletion. Exposure for IL-2 will be listed only. 
7.8.2 
ADVERSE EVENTS 
TEAEs are those events with onset at/or after the first administration of any study drug of the 
regimen (acimtamig,  AlloNK® or any study treatment such as lymphodepletion or IL-2) until 30 
days after last administration of any study drug.  
Lymphodepletion-TEAEs (LTEAEs) are the TEAEs with onset at/or after the date of the first 
lymphodepletion and before the first administration of acimtamig or AlloNK®. 
The acimtamig/AlloNK®-TEAEs (ATEAEs) are the TEAEs with onset at/or after the first 
administration of acimtamig or AlloNK®. 
TEAEs and SAEs will be coded using MedDRA, version 26 or later, and graded using NCI CTCAE 
v5.0 (including neurotoxicities that are not considered ICANS) except for CRS and ICANS, which 
will be graded according to the ASTCT grading, tumor lysis syndrome (TLS) will be graded 
according to the Cairo-Bishop TLS grading system and acute GVHD will be grading according to 
the Mount Sinai Acute GvHD International Consortium (MAGIC) criteria. 
Changes in the severity of one and the same AE will be collected as separate records in the eCRF, 
but they will be linked. As it is only a change of grading in one and the same AE, such an AE will 
be counted only once in AE tables, using the highest grade reported. If such an AE is recorded 
as both serious and non-serious, it will be counted as serious AE in the tables. If such an AE is 
recorded as both related (possibly, probably, definitely related) and not-related, it will be counted 
as related AE in the tables.  
The number and percentage of participants with an AE and the number of AEs will be summarized 
for the following TEAEs: 
x 
TEAE, serious TEAE, LTEAE, serious LTEAE, ATEAE, serious ATEAE 
x 
AE of special interest (AESI)  
x 
TEAE of severity grade 3, 4 or 5 for CTCAE 5.0, ASTCT, ASTCT ICANS, MAGIC, Cairo-
Bishop grading 
x 
TEAE and serious TEAE related to acimtamig, to AlloNK® and to acimtamig or AlloNK®; 
an AE is considered a study drug related if it is possibly, probably or definitely related 
according to eCRF 
x 
TEAE of CTCAE Grade 3, 4 or 5 related to acimtamig, to AlloNK® and to acimtamig or 
AlloNK® 
x 
TEAE leading to acimtamig interruption, to AlloNK® interruption, to permanent 
discontinuation of acimtamig, to permanent discontinuation of AlloNK® 
x 
Fatal TEAE, fatal TEAE related to acimtamig, fatal TEAE related to AlloNK® 
x 
TEAE of preferred term “Infusion-Related Reactions” 
The summary described above will be repeated for participants who received and who did not 
receive IL-2 in each cohort. 
The incidence of following TEAEs will be tabulated by system organ class (SOC) and preferred 
term (PT): 










Statistical Analysis Plan: AFM13-203 
Review Status: Final 
 
Version: 2.0 
 
Version Date: 20-SEP-2024 
 
 
 
CONFIDENTAL 
Page 26 of 26 
Statistical Analysis Plan template version 1.0 dated 29-Oct-2020 
 
12. 
PROGRAMMING SPECIFICATIONS 
All outputs will be produced using SAS version 9.4 or a later version. 
The margins should be at least 1.50 inches for the binding edge and 1.0 inches for all others.  
In the top left portion of each table/listing, the protocol number will be presented. On the next line, 
a table/listing number followed by the title of the table/listing and population information will be 
displayed. Horizontal lines will appear after the column heading of the table/listing. Footnotes will 
be put under the main body of text at the bottom of the page. The source listing number will be 
displayed for all tables. The SAS program name will appear on the bottom left corner of each 
table/listing in a string, followed by the database lock date, and the page number will appear on 
the bottom right corner of each table/listing. The date and time of creation of the table/listing will 
appear on the bottom left corner under to the SAS program name line.  
Courier New 8-point bold font will be used for all tables and listings. Usually, a landscape layout 
is suggested for both tables and listings, but it is not mandatory. Any date information in the listing 
will use the date9. format, for example, 07MAY2002. 
The list of tables, listings, and figures, and shells for unique tables are provided in a separate 
Mock-Up tables, figures, and listings (TFLs) document. 
13. 
REFERENCES 
Koyama T, Chen H. Proper inference from Simon’s two-stage designs. Stat Med. 
2008;27(16):3145-3154. Doi:10.1002/sim.3123.