A Phase II Open-label Multicenter Study to Assess the Efficacy and Safety of AFM13 in Patients With Relapsed or Refractory CD30-positive Peripheral T-cell Lymphoma or Transformed Mycosis Fungoides (REDIRECT)
Phase: PHASE2
Conditions: Peripheral T Cell Lymphoma, Transformed Mycosis Fungoides
Sponsor: Affimed GmbH

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CLINICAL STUDY PROTOCOL 
 
A Phase II Open-label Multicenter Study to Assess the 
Efficacy and Safety of AFM13 in Patients with Relapsed or 
Refractory CD30-positive Peripheral T-cell Lymphoma or  
Transformed Mycosis Fungoides (REDIRECT) 
 
 
Protocol No.:   AFM13-202 
 
Version No:   
V7.0  
 
Version Date:   31 May 2023 
 
EudraCT No.: 2019-001003-20 
 
IND No.:   
107652 
 
Protocol version history: 
Protocol V1.0 dated 20 February 2019 
Protocol V2.0 dated 26 March 2019 
Protocol V3.0 dated 07 June 2019 
Protocol V4.0 dated 02 July 2020 
Protocol V5.0 dated 29 June 2021 (note: V5.0 signed but not distributed) 
Protocol  V6.0 dated 12 July 2021 
 
Affimed GmbH 
Im Neuenheimer Feld 582  
69120 Heidelberg  
Germany 
 
The information contained in this document, especially unpublished data, is confidential 
communication from Affimed. Acceptance of this document constitutes the agreement of the recipient 
that this information will not be disclosed to others without written authorization from Affimed, except 
to the extent necessary for Ethics Committee/Institutional Review Board procedures and to obtain 

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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 eg, 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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OTHER CONTACT INFORMATION 
Full contact details for each Investigational site, the Sponsor, the Medical Monitor(s), and key 
coordinating and operational personnel will be maintained in the Trial Master File and in each 
site’s Study File throughout the course of the study. 
 
 
 
 

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PROTOCOL SYNOPSIS 
Study Title 
A Phase II Open-label Multicenter Study to Assess the Efficacy and 
Safety of AFM13 in Patients with Relapsed or Refractory 
CD30-positive Peripheral T-cell Lymphoma or Transformed 
Mycosis Fungoides (REDIRECT) 
Investigational 
Product 
AFM13 
Protocol Number 
AFM13-202 
EudraCT Number 
2019-001003-20 
IND Number 
107652 
Sponsor and 
Contract Research 
Organization 
Sponsor: Affimed GmbH 
Contract Research Organization : ICON plc 
Study Phase 
2 
Study Regions 
North America, Europe and Asia Pacific. 
Number of Subjects 
Up to 150 subjects in total: approximately 100 (maximum of 103) 
subjects in Cohort A (peripheral T-cell lymphoma [PTCL]; defined 
as CD30-positive ≥10% by centrally assessed Ber-H2 targeted 
immunohistochemistry [IHC]), 20 subjects (maximum of 25) in 
Cohort B (PTCL; defined as CD30-positive ≥1% to <10% by 
centrally assessed Ber-H2 targeted IHC), and approximately 20 
(maximum of 22) subjects in Cohort C (transformed mycosis 
fungoides [TMF]; defined as CD30-positive ≥1% by centrally 
assessed Ber-H2 targeted IHC). 
Study Objectives 
PRIMARY: 
• 
To assess the antitumor activity of AFM13 by Independent 
Review Committee confirmed positron emission 
tomography-computed tomography (PET-CT)-based 
objective response rate (ORR) 
SECONDARY: 
• 
To assess the antitumor activity of AFM13 by Independent 
Review Committee -confirmed complete response (CR) and 
partial response (PR) rates and CT scan-based ORR 
• 
To assess the antitumor activity of AFM13 by Investigator-
assessed ORR (defined as ORR-2) 
• 
To assess the duration of response (DOR) to AFM13 
• 
To assess the safety and tolerability of AFM13 
• 
To assess the pharmacokinetics (PK) of AFM13 

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Inclusion and 
Exclusion Criteria 
INCLUSION CRITERIA: 
1. Written informed consent in accordance with federal, local, and 
institutional guidelines. 
2. Age ≥18 years at time of provision of informed consent. 
3. Histologically confirmed CD30-positive (via centrally assessed 
Ber-H2 targeted IHC; cut-offs listed below) PTCL (allowed 
subtypes listed below) or TMF per the revised World Health 
Organization 
2016 
classification 
(Swerdlow, 
2016). 
(Note: Subjects must wait for central results before first dose of 
study drug) 
The PTCL subtypes allowed for Cohorts A and B: 
• 
Enteropathy-associated T-cell lymphoma 
• 
Monomorphic epitheliotropic intestinal T-cell lymphoma 
• 
Hepatosplenic T-cell lymphoma 
• 
Subcutaneous panniculitis-like T-cell lymphoma 
• 
Peripheral T-cell lymphoma, not otherwise specified 
• 
Angioimmunoblastic T-cell lymphoma 
• 
Follicular T-cell lymphoma 
• 
Nodal peripheral T-cell lymphoma with T-follicular helper 
phenotype 
• 
Anaplastic large-cell lymphoma, anaplastic lymphoma 
kinase (ALK)-positive 
• 
Anaplastic large-cell lymphoma, ALK-negative 
• 
Breast implant–associated anaplastic large-cell lymphoma 
The required cut-offs for the CD30-positivity are: 
• Cohort A (PTCL): ≥10% by IHC 
• Cohort B (PTCL): ≥1% to <10% by IHC 
• Cohort C (TMF): ≥1% by IHC 
Note: After the planned Interim Analyses, Cohorts A and B may 

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subjects with CD30 positive ≥ 1% to <10% by IHC, and Cohort C 
(TMF) subjects with CD30 expression ≥1% by IHC. All three 
cohorts will be analyzed independently as described below. 
Analysis Sets: 
The full analysis set (FAS) following the intent to treat principle 
will consist of all subjects who received at least one dose of 
AFM13. The FAS will be the primary population for all efficacy 
related endpoints and the primary objective; an additional sensitivity 
analysis for all subjects who received at least one dose of AFM13 
and had at least one post-baseline efficacy assessment will be 
conducted to support the results of the primary analysis.  
The safety set will consist of all subjects who received at least one 
dose of AFM13 and had at least one post-baseline safety 
assessment, where the statement that a subject had no AE on the AE 
Case Report Form constitutes a safety assessment. The safety set 
will be the primary population for all safety related endpoints. 
Additional analysis sets for sensitivity analyses may be introduced 
in the statistical analysis plan due to the coronavirus disease-2019 
pandemic. 
Missing Data/Discontinuation: 
As this is a non-randomized study design, no missing imputation of 
missing values will be done for any analysis except for 
partial/missing AE dates and concomitant medication dates. 
Reasons for discontinuation of the study and the study drug will be 
listed and summarized. 
Efficacy Analyses: 
ORR (CR+PR) N will be summarized using descriptive statistics 
and 95% confidence limits. In addition, CR and PR will be 
presented separately.
 
 
 
Safety Analyses: 
AEs, related AEs, serious AEs (SAEs) and related SAEs, AEs with 
NCI CTCAE Grades ≥3, related AEs of NCI CTCAE Grades ≥3, 
AEs leading to premature discontinuation, interruptions or 
discontinuation of study drug or dose modification will be analyzed 

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descriptively utilizing corresponding Medical Dictionary for 
Regulatory Activities System Organ Classes and Preferred Terms. 
Safety laboratory results will be graded by NCI CTCAE v5.0 (or 
higher). If no grading exists, then values will be classified into 
low/normal/high based on laboratory normal ranges. Each 
parameter will be presented by descriptive statistics at each visit 
including change from baseline (Screening). Shift tables for 
CTCAE grades and reference ranges will be presented. All 
laboratory values will be listed. A separate listing for abnormal lab 
values (≥Grade 3, and low/high values) will be presented. Vital 
signs will be summarized by descriptive statistics at each visit 
including change from baseline will be presented and a listing will 
be provided. 
Interim Analysis: 
An interim analysis will be performed for Cohorts A and B 
independently, with all subjects enrolled at or prior to the cut-off 
date defined as the completion of the 20th subject for each cohort. 
 
 
 
 
 
 
 
Sample Size: 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
PROTOCOL SYNOPSIS ..................................................................................................................5 
1 
INTRODUCTION ................................................................................................................... 23 
1.1 
Targeting Unique Cell Surface Proteins in Lymphoma ......................................................... 23 
1.2 
CD30-positive Lymphoid Malignancies............................................................................... 23 
1.2.1 
Peripheral T-cell Lymphoma ....................................................................................... 24 
1.2.2 
Transformed Mycosis Fungoides ................................................................................. 24 
1.3 
AFM13 ............................................................................................................................. 25 
1.3.1 
Pharmaceutical and Therapeutic Background................................................................ 25 
1.3.2 
Nonclinical Studies ..................................................................................................... 26 
1.3.2.1 
Characterization of Affinity and Specificity .............................................................. 27 
1.3.2.2 
Primary Pharmacodynamics Activity........................................................................ 27 
1.3.2.3 
Secondary Pharmacodynamics Activity .................................................................... 27 
1.3.2.4 
Safety Pharmacology............................................................................................... 28 
1.3.2.5 
 28 
1.3.3 
AFM13 Clinical Experience ........................................................................................ 28 
1.3.3.1 
Phase 1 First-in-Human Clinical Trial in Relapsed/Refractory Hodgkin Lymphoma .... 28 
1.3.3.2 
Phase 1b/2a Clinical Trial in CD30-positive Lymphoma with Cutaneous Involvement 30 
1.3.3.3 
Phase 1b Clinical Trial of AFM13 in Combination with Pembrolizumab in Patients with 
Relapsed or Refractory Classical Hodgkin Lymphoma ............................................................. 31 
1.4 
Rationale for Dose Selection ............................................................................................... 32 
1.5 
Safety Guidance Information for Investigators ..................................................................... 34 
2 
STUDY OBJECTIVES AND ENDPOINTS ............................................................................ 35 
2.1 
Estimand for the Primary Objective..................................................................................... 36 
3 
SUBJECT ELIGIBILITY AND ENROLLMENT ................................................................... 38 
3.1 
Inclusion Criteria ............................................................................................................... 38 
3.2 
Exclusion Criteria .............................................................................................................. 40 
3.3 
Process for Subject Enrollment ........................................................................................... 42 
3.4 
Definition of Evaluable Subject and Replacement of Subjects ............................................... 42 
3.5 
Reasons for Withdrawal of Subject from Study .................................................................... 42 
3.6 
Subject Compliance, Lost to Follow-up, and Procedures for Subject Discontinuation ............. 43 
3.7 
Study or Site Termination ................................................................................................... 43 
4 
STUDY DESIGN ..................................................................................................................... 45 
5 
STUDY SCHEDULE............................................................................................................... 46 
5.1 
Study Periods..................................................................................................................... 46 
5.1.1 
Pre-screening and Screening Period ............................................................................. 46 
5.1.2 
Treatment Period ........................................................................................................ 47 

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5.1.3 
Efficacy and Safety Follow-up Period .......................................................................... 47 
5.1.4 
Follow-up .................................................................................................................. 47 
5.1.5 
End of Study .............................................................................................................. 47 
5.2 
Schedule of Assessments .................................................................................................... 47 
5.3 
Volume of Blood Sampling ................................................................................................ 58 
5.4 
Description of Study Interventions and Assessments ............................................................ 59 
5.4.1 
Confirmation of CD30-positivity and ALK Status......................................................... 59 
5.4.2 
Medical History.......................................................................................................... 60 
5.4.3 
Pregnancy and Follicle Stimulating Hormone Tests ...................................................... 60 
5.4.4 
Eastern Cooperative Oncology Group Performance Score ............................................. 60 
5.4.5 
Vital Signs ................................................................................................................. 60 
5.4.6 
Physical Examinations ................................................................................................ 60 
5.4.7 
Clinical Chemistry, Hematology, Coagulation, and Urinalysis ....................................... 61 
5.4.8 
Electrocardiogram ...................................................................................................... 61 
5.4.9 
Disease Assessment .................................................................................................... 61 
5.4.10 
Response Assessment ................................................................................................. 62 
5.4.11 
Exploratory Biomarkers .............................................................................................. 63 
5.4.12 
Cytokines ................................................................................................................... 63 
5.4.13 
Anti-drug Antibodies .................................................................................................. 63 
5.4.14 
Pharmacokinetic Sampling .......................................................................................... 63 
5.4.15 
Quality of Life Assessment ......................................................................................... 64 
6 
STUDY MEDICATION AND ADMINISTRATION ............................................................... 65 
6.1 
Provision and Replacement of AFM13 ................................................................................ 65 
6.2 
Labelling of AFM13 .......................................................................................................... 66 
6.3 
Storage of AFM13 ............................................................................................................. 66 
6.4 
Drug Accountability ........................................................................................................... 66 
6.5 
Premedication Regimen and Post Dose Observation ............................................................. 67 
6.6 
AFM13 Dosing Instructions................................................................................................ 67 
6.7 
Duration of Treatment ........................................................................................................ 68 
6.8 
AFM13 Dose Delays or Interruptions .................................................................................. 68 
6.9 
Permitted and Restricted Concomitant Medications .............................................................. 72 
6.9.1 
Acceptable Concomitant Medications .......................................................................... 72 
6.9.1.1 
Highly Effective Contraception ................................................................................ 72 
6.9.2 
Prohibited Concomitant Medications ........................................................................... 73 
6.10 
Blinding and Procedures for Unblinding the Study ............................................................... 73 
7 
ADVERSE EVENTS AND REPORTING REQUIREMENTS ................................................ 74 
7.1 
Assessment of Safety ......................................................................................................... 74 
7.2 
Adverse Event Definition ................................................................................................... 74 
7.3 
Importance of Adverse Event Reporting .............................................................................. 75 
7.4 
Evaluating Adverse Events ................................................................................................. 75 

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9.1 
Data Recording, Monitoring of the Study and Regulatory Compliance .................................. 87 
9.2 
Study Monitoring ............................................................................................................... 87 
9.3 
Clinical Study Audit........................................................................................................... 88 
9.4 
Clinical Study Report ......................................................................................................... 88 
9.5 
Data Availability................................................................................................................ 88 
9.6 
Curricula Vitae and Financial Disclosure of Investigators ..................................................... 88 
9.7 
Protocol Modifications ....................................................................................................... 88 
10 
ETHICAL CONSIDERATIONS ......................................................................................... 89 
10.1 
Ethical Conduct of the Study .............................................................................................. 89 
10.2 
Informed Consent .............................................................................................................. 89 
10.3 
Patient Participation Card ................................................................................................... 90 
10.4 
Insurance ........................................................................................................................... 91 
10.5 
Institutional Review Board/Independent Ethics Committee ................................................... 91 
10.6 
Subject Privacy .................................................................................................................. 91 
11 
DATA CONFIDENTIALITY AND PUBLICATION POLICY ........................................... 92 
12 
DATA HANDLING AND RECORD KEEPING.................................................................. 93 
12.1 
Recording of Data .............................................................................................................. 93 
12.2 
Study Record Retention ...................................................................................................... 93 
 
 
 
 
 
 
 
 
REFERENCES ............................................................................................................................. 120 
 
 
 
 
 

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List of Tables 
Table 1: AFM13 Dose and Schedule for Study AFM13-102 ................................................................ 30 
Table 2: Study Objectives and Endpoints ........................................................................................... 35 
Table 3: Characteristics of AFM13 for IV Infusion ............................................................................. 65 
Table 4: Management of AFM13 Associated Infusion-Related Reactions* ........................................... 70 
Table 5: Contact Information for SAE Reporting ................................................................................ 79 
Table 6: Pharmacokinetic Parameters ................................................................................................. 84 
 
 
List of Figures 
Figure 1: AFM13 Structure ............................................................................................................... 26 
Figure 2: Study Design ..................................................................................................................... 45 
Figure 3: Sample Patient Participation Card........................................................................................ 90 
 
 
 
 

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LIST OF ABBREVIATIONS 
 
ADA 
anti-drug antibodies 
AE 
adverse event 
ALCL  
anaplastic large cell lymphoma  
ALK 
anaplastic lymphoma kinase 
AUC 
area under the concentration versus time curve 
AUC0-∞ 
AUC from time zero to infinity 
AUC0-t 
AUC from time zero to time t 
BSA 
body surface area 
BV 
brentuximab vedotin; brentuximab; Adcetris® 
CAILS 
Composite Assessment of Index Lesions Severity 
CD 
cluster of differentiation 
CHOP 
cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), 
vincristine sulfate (Oncovin), and prednisone 
Cmax 
maximum concentration 
COVID-19 
coronavirus disease 2019 
CR 
complete response/remission 
CRA 
Clinical Research Associate 
CT 
computed tomography 
CTCAE 
common terminology criteria for adverse events 
CTCL 
cutaneous T-cell lymphoma 
DLT 
dose limiting toxicity 
DOR 
duration of response 
EC 
Ethics Committee(s) 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic Case Report Form 
EOI 
end of infusion 
EPOCH 
etoposide phosphate, prednisone, vincristine sulfate (Oncovin), 
cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin) 
EQ-5D 
European Quality of Life 5-Dimensional  
FAS 
full analysis set 
FDA 
(US) Food and Drug Administration 
FDG 
fluorodeoxyglucose 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GvHD 
graft versus host disease 
H1/H2 
histamine 1/histamine 2 
HCT 
hematopoietic stem cell transplantation 
HIV 
Human Immunodeficiency Virus 
HL 
Hodgkin lymphoma 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation  
IHC 
immunohistochemistry 
IND 
Investigational New Drug 

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IPI 
International Prognostic Index 
IRB 
Institutional Review Board 
IRC 
Independent Review Committee 
IRR 
infusion-related reaction 
IV 
intravenous(ly) 
MedDRA 
Medical Dictionary for Regulatory Activities 
MF 
mycosis fungoides 
MRI 
magnetic resonance imaging 
mSWAT 
modified Severity Weighted Assessment Tool 
NCI  
National Cancer Institute  
NHL 
non-Hodgkin lymphoma 
NK 
natural killer 
NYHA 
New York Heart Association 
ORR 
objective (or overall) response rate 
OS 
overall survival 
PBMC 
peripheral blood mononuclear cells 
PD 
progressive disease 
PET 
positron emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PR 
partial response 
PS 
performance score 
PT 
preferred term 
PTCL 
peripheral T-cell lymphoma 
QxW 
every x weeks 
QOL 
quality of life 
R/R 
relapsed or refractory 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
sCD30 
soluble CD30 
SUSAR 
suspected unexpected serious adverse reaction 
t½ 
half-life 
TEAE 
treatment emergent adverse event 
TMF 
transformed mycosis fungoides  
TNF 
tumor necrosis factor 
ULN 
upper limit of normal 
US 
United States (of America) 
Vss 
volume of distribution at steady state 
WHO 
World Health Organization 
 
 
 
 
 

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1 
INTRODUCTION 
1.1 
Targeting Unique Cell Surface Proteins in Lymphoma 
Non-Hodgkin lymphoma (NHL) is a heterogeneous group of lymphoproliferative malignancies 
with multiple histological subtypes. It is estimated that approximately 65,540 new cases of NHL 
were diagnosed in 2010 and 20,210 patients died of their disease (Jemal, 2010). Based on the 
World Health Organization (WHO) classification of hematological and lymphoid tumors, NHL 
can be broadly classified as B or T/natural killer (NK)-cell neoplasms (Campo, 2011). In the 
United States of America (US), about 85% of cases are categorized as B-cell lymphomas and 
15% are categorized as T/NK-cell lymphomas (Jemal, 2010). 
The expression of unique proteins on the cell surface allows for the identification and differential 
diagnosis of lymphoid malignancies. Several cell markers have been exploited as treatable 
targets by immunotherapeutics, such as rituximab, a genetically-engineered chimeric 
immunoglobulin G1 monoclonal antibody that targets cluster of differentiation (CD)20, and 
brentuximab vedotin ([BV] Adcetris®), an antibody drug conjugate targeting CD30. CD30, a 
member of the tumor necrosis factor (TNF)-receptor superfamily, has pleiotropic biologic 
functions, and antibodies targeting CD30 and other TNF family receptors can exhibit both 
agonistic and antagonistic signaling functions. CD30 was identified in the early 1980s as a 
protein recognized by monoclonal antibody Ki-1 (Schwab, 1982) and abundantly and selectively 
expressed on the surface of Hodgkin and Reed-Sternberg cells. Later, its expression in other 
neoplastic cells such as anaplastic large cell lymphoma (ALCL), and other lymphoid 
malignancies as well as on several non-lymphoid malignancies including selected germ cell 
tumors was demonstrated. Expression of CD30 on normal cells is highly restricted, thereby 
allowing differential targeting of malignant cells. Brentuximab vedotin has shown striking 
efficacy in Phase 1, 2, and 3 trials, with manageable toxicity, and is approved for the treatment of 
classical Hodgkin lymphoma (HL), systemic ALCL and in primary cutaneous ALCL or CD30-
expressing mycosis fungoides (MF). These results provide clinical validation for therapeutic 
targeting of CD30 in the setting of HL, ALCL, and cutaneous T-cell lymphoma (CTCL). 
1.2 
CD30-positive Lymphoid Malignancies 
In hematologic malignancies, CD30 expression is strongly increased in HL and ALCL, but has 
also been noted in other lymphoid malignancies, such as diffuse large B-cell lymphoma , 
including primary mediastinal (thymic) large B-cell lymphoma , peripheral T-cell lymphoma 
(PTCL), lymphomatoid papulosis, MF, and Epstein-Barr virus -driven clonal 
lymphoproliferative disease enteropathy-associated T-cell lymphoma type I, human T-cell 
lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma, and primary effusion 
lymphoma harboring human herpes virus-8 (Bhatt, 2013; Sibon, 2016; Hu, 2013; Lunning, 2012; 
de Leval, 2010). Additionally, primary CTCL represents a heterogeneous group of neoplasms 
derived from skin-homing T-cells that also regularly expresses CD30.  

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1.2.1 
Peripheral T-cell Lymphoma 
Peripheral T-cell lymphomas are a heterogeneous group of aggressive lymphomas that make up 
~15% of all NHLs in adults. Some of the many known subtypes include PTCL, not otherwise 
specified, ALCL, and angioimmunoblastic T-cell lymphoma. 
While the identified subtype of the PTCL can lead to different survival rates and initial treatment 
options, in general without treatment the survival of PTCL patients is measured in months. With 
combination chemotherapy (eg, cyclophosphamide, doxorubicin hydrochloride 
(hydroxydaunorubicin), vincristine sulfate (Oncovin®), and prednisone [CHOP] or etoposide 
phosphate, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, and doxorubicin 
hydrochloride (hydroxydaunorubicin) [EPOCH]), 5-year overall survival (OS) rates range from 
49 to 74% for those patients with low to intermediate scores (scores 0 to 2) on the International 
Prognostic Index (IPI); however, such low-intermediate risk patients are not common and the 
5-year OS after combination chemotherapy for the more common patients with the IPI scores 
of 3 or 4 to 5 are 21 and 6%, respectively (Sonnen, 2005). 
The poor outcomes with chemotherapy have led to more aggressive approaches such as 
autologous hematopoietic stem cell transplantation (HCT) or radiation therapy as consolidation. 
The use of autologous HCT may depend on the subtype of PTCL and the IPI score. 
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 HCT, with estimates as 
low as a median progression-free survival (PFS) and OS of 3 and 6 months, respectively (Mak, 
2013; Biasoli, 2015; Bellei, 2018). 
No optimal therapy is defined for relapsed or refractory (R/R) PTCL with the exception of BV 
for the ALCL subtype and there is sparsity of data regarding long term outcomes for these 
patients. For those patients who are potential candidates for autologous or allogeneic HCT, 
achieving an objective response as a bridge to transplant is vitally important (Laribi, 2018; 
Corradini, 2004; Le Gouill, 2008; Jacobsen, 2011; Goldberg, 2012). 
1.2.2 
Transformed Mycosis Fungoides 
Mycosis fungoides is the most common subtype of primary CTCL and is a mature T-cell 
lymphoma with cutaneous presentation but with potential systemic involvement. 
Advanced stage is considered to be a persistent disease with multiple relapses. Due to the chronic 
nature of the condition, the choice of therapy depends on the goals of therapy, including 
long-term disease control, symptom relief to increase quality of life and addressing more 
clinically aggressive disease. 
Once the disease is widespread, systemic therapies are needed as skin-directed therapies are 
insufficient for treatment (Whittaker, 2003; Trautinger, 2006; Willemze and Dreyling, 2010; 
NCCN Clinical Practice Guidelines in Oncology V2.2021; Sugaya, 2013; Olsen, 2011). Such 
systemic approaches include single agent or combination therapies; with agents considered to be 

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immune-preserving (eg, retinoids, low dose methotrexate) or immunostimulatory (eg, interferon) 
being utilized first (Jawed, 2014a; Jawed, 2014b). Other systemic therapies include 
phototherapy, histone deacetylase inhibitors, BV, and alemtuzumab. 
Large cell transformation, which is the histopathological transformation of neoplastic 
lymphocytes to a clonally identical large cell phenotype (Wolfe, 1995, Wood, 1993), occurs in 
20 to 50% of patients with advanced MF. Such transformation is often associated with poor 
prognosis and is associated with mean 5-year OS of less than 20% (Salhany, 1988). CD30 
expression is also associated with a reduced survival and often seen in diseases with large cell 
transformation leading to a more aggressive clinical course (Benner, 2012). 
Currently the only known curative therapy for patients with transformed mycosis fungoides 
(TMF) is allogeneic HCT and the patients are in dire need for other therapeutic options. 
1.3 
AFM13 
Please refer to the Investigator’s Brochure (IB) for additional details of non-clinical and clinical 
studies conducted with AFM13. 
1.3.1 
Pharmaceutical and Therapeutic Background 
The investigational medicinal product AFM13 is a tetravalent bispecific chimeric (anti-human 
CD30 x anti-human CD16A) recombinant antibody construct that is being developed for the 
indication of HL (Reusch, 2014) and other CD30-postive T-cell malignancies. 
 
 
 
 
 
 

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1.3.2.1 
Characterization of Affinity and Specificity 
 
 
 
 
 
 
 
 
 
 
 
1.3.2.2 
Primary Pharmacodynamics Activity 
 
 
 
 
 
 
 
  
1.3.2.3 
Secondary Pharmacodynamics Activity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1.3.2.4 
Safety Pharmacology 
 
 
 
 
1.3.2.5 
Tissue Cross Reactivity 
 
 
 
 
 
 
 
 
 
 
1.3.3 
AFM13 Clinical Experience 
A first-in-human Phase 1 study with AFM13 was conducted and completed in patients with R/R 
HL (AFM13-101). Currently, there are three ongoing clinical studies with AFM13 in patients 
with CD30-positive lymphoid malignancies, namely, AFM13-102 (R/R T-cell lymphoma), 
AFM13-103 (R/R HL), and AFM13-201 (R/R HL). Data from the clinical studies AFM13-101 
and AFM13-103 which informed this study design are provided below. 
1.3.3.1 
Phase 1 First-in-Human Clinical Trial in Relapsed/Refractory Hodgkin 
Lymphoma 
The clinical first-in-human study, AFM13-101, was conducted in patients with heavily pre-
treated R/R HL (Rothe, 2015). Escalating doses of AFM13 were administered to determine the 
safety and tolerability of AFM13. Twenty-eight patients (16 males, 12 females) were enrolled 
and received treatment with AFM13 in 8 dose cohorts. Twenty-four patients received increasing 
doses of AFM13 ranging from 0.01 to 7.0 mg/kg on a weekly dosing schedule for 4 weeks. In 
addition, 4 patients were treated with 4.5 mg/kg twice weekly for 4 weeks.   
The median age was 38.5 years (range 19 to 72 years). Fourteen of the 28 patients (50%) had 
refractory disease and the remainder had relapsed disease; all were CD30-positive. Patients had 
received a median of 6 (range 3 to 11) previous lines of therapy for HL. Twenty-four patients 

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(85.7%) had previously received radiotherapy and 22 patients (78.6%) had previously undergone 
stem cell transplantation. Nine patients had previously received BV. 
All 28 patients were included in the Safety population, 2 patients had to be excluded from the 
Efficacy population: 1 patient withdrew the informed consent; 1 patient discontinued due to 
adverse events (AEs) of pneumonia and multi-organ failure. Twenty-three of the 28 patients 
experienced at least one AE which was evaluated as treatment-related by the Investigator. Most 
AEs were mild or moderate; only 18 of 196 (9.2%) of documented AEs were National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥3. One 
dose limiting toxicity (DLT) was documented; Grade 4 hemolytic anemia considered possibly 
related to AFM13. The patient subsequently died due to aspergillus pneumonia and multi-organ 
failure which was assessed as not/unlikely to be related to study drug. The most frequent AEs 
were symptoms associated with infusion-related reactions including pyrexia, chills, headache and 
nausea. Treatment-associated infections were rare; nasopharyngitis and pneumonia was 
documented in 5 and 4 patients, respectively.  
After review of the safety data, the Independent Data Monitoring Committee concluded that the 
maximum feasible dose of 7 mg/kg following a weekly dose schedule was reached without 
toxicity concerns or reaching the maximum tolerated dose. Additionally, the 4 patients treated 
with 4.5 mg/kg twice weekly completed the treatment without toxicity concerns of the 
Independent Data Monitoring Committee. Apart from the DLT event, administration of AFM13 
was not associated with clinically significant changes in any laboratory parameters, nor was it 
associated with clinically significant changes in any vital signs or electrocardiogram (ECG) 
parameters.  
Twenty-six of 28 patients were eligible for efficacy evaluation. No patients had a complete 
response (CR) and 3 of 26 patients had a partial response (PR) at the final study visit. The 
objective response rate (ORR) (CR + PR) was 11.5%. At the end of study assessment 13 patients 
(50%) had stable disease and 10 patients (38.5%) had disease progression. 
Overall, the effect of AFM13 treatment was more pronounced in patient cohorts with AFM13 
doses ≥1.5 mg/kg with an ORR of 23% (3/13).  
 
 
 
 
 

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The most commonly observed AE has been rigors, a symptom known to be associated with 
infusion-related reaction (IRR), which occurred during AFM13 infusions and was considered 
related to AFM13. These AEs were all Grade 1 in severity. 
1.3.3.3 
Phase 1b Clinical Trial of AFM13 in Combination with Pembrolizumab in 
Patients with Relapsed or Refractory Classical Hodgkin Lymphoma 
AFM13-103 was an open label Phase 1b dose escalation study to assess the safety of AFM13 in 
combination with pembrolizumab in patients with R/R classical HL. The study consisted of Part 
1 (dose escalation) and Part 2 (extension study). Part 1 was 3+3 dose escalation design and Part 2 
was dose extension study with optional translational substudy. Treatment duration for AFM13 
was until Week 25 and treatment duration for pembrolizumab was up to Week 52. In Part 1 (dose 
escalation), the AFM13 was escalated in sequential cohorts, while the dose of pembrolizumab 
was fixed at 200 mg once every 3 weeks (Q3W). 
A total of 30 patients (12 in Part 1 [dose escalation] and 18 in Part 2 [extension study]) were 
analyzed for safety and efficacy; 10 patients completed all 52 weeks of study drug. 
The maximum tolerated dose was not exceeded and the minimal activation dose was determined 
to be 7 mg/kg. Overall, all 30 patients experienced at least one treatment emergent adverse 
events (TEAEs). The most frequently reported events by preferred terms (PTs) were infusion 
related reaction (28 [93.3%] patients), nausea (12 [40.0%] patients), pyrexia (12 [40.0%] 
patients), diarrhea (10 [33.3%] patients), rash (10 [33.3%] patients), upper respiratory tract 
infection (9 [30.0%] patients), cough (8 [26.7%] patients), fatigue (8 [26.7%] patients), headache 
(7 [23.3%] patients), pruritus (7 [23.3%] patients), alanine aminotransferase increased (6 [20.0%] 
patients), and vomiting (6 [20.0%] patients). 
 
 
 
 
 
 
 
 

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The ORR was 83.3% (25/30 patients) with 95% CI of 65.3, 94.4. CR was observed in 11 
(36.7%) patients and partial response was observed in 14 (46.7%) patients: Stable disease was 
observed in 2 (6.7%) patients and progressive disease was observed in 10.0% (3 patients). 
1.4 
Rationale for Dose Selection 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1.5 
Safety Guidance Information for Investigators 
Throughout the study, Investigators should refer to the current edition of the IB for a full review 
of the potential risks associated with treatment with AFM13 and details of expected AEs. 

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The estimand corresponding to the primary objective consists of: 
• Population: defined through appropriate inclusion/exclusion criteria to reflect the targeted 
subject population for approval.  
• Variable: Response assessment from the first assessment as assessed by the modified 
Lugano Classification (Cheson, 2014) for Cohorts A and B (PTCL) and after at least 
8 weeks from the first assessment as assessed by Olsen Criteria (Olsen, 2011) for 
Cohort C (TMF) 
 
• Intercurrent event strategy will follow the treatment policy strategy: subjects non-
evaluable for efficacy will not be replaced.  
Subjects with missing post-baseline response assessment will be classified as non-
responders regardless of the reason. 
 
 
  
• Population-level summary: Percentage of subjects achieving an overall response. 
Estimator: Best objective response rate assessed via positron emission tomography (PET)-
computed tomography (CT) and evaluated by independent central review, for all subjects in the 
full analysis set (FAS). 
Sensitivity estimand:
 
 
 
 
 

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3 
SUBJECT ELIGIBILITY AND ENROLLMENT 
For Cohorts A, B and C, subjects who meet all the following inclusion criteria and none of the 
exclusion criteria will be enrolled into the study. 
Subjects who express CD30 (≥10% CD30 expression for PTCL subjects in Cohort A, ≥1% to 
<10% CD30 expression for PTCL subjects in Cohort B, and ≥1% CD30 expression for TMF 
subjects in Cohort C) by centrally assessed Ber-H2 targeted immunohistochemistry (IHC) 
(Section 5.4.1), and who have received at least one prior line of systemic therapy and have 
progressed on, or are not eligible for all standard approved therapy, will be enrolled in this study. 
Subjects with PTCL will be enrolled to Cohorts A or B and subjects with TMF will be enrolled 
to Cohort C. The specific subtypes for the PTCL cohorts are listed under the Inclusion Criteria 
(Section 3.1). After the planned Interim Analyses, Cohorts A and B may be combined to include 
subjects with ≥1% CD30 expression. 
3.1 
Inclusion Criteria 
1. 
Written informed consent in accordance with federal, local, and institutional guidelines. 
2. 
Age ≥18 years at time of provision of informed consent. 
3. 
Histologically confirmed CD30-positive (via centrally assessed Ber-H2 targeted IHC; 
cut-offs listed below) PTCL (allowed subtypes listed below) or TMF per the revised WHO 
2016 classification (Swerdlow, 2016) (Note: Subjects must wait for central results before 
first dose of study drug). 
The PTCL subtypes allowed for Cohorts A and B: 
• 
Enteropathy-associated T-cell lymphoma 
• 
Monomorphic epitheliotropic intestinal T-cell lymphoma 
• 
Hepatosplenic T-cell lymphoma 
• 
Subcutaneous panniculitis-like T-cell lymphoma 
• 
Peripheral T-cell lymphoma, not otherwise specified 
• 
Angioimmunoblastic T-cell lymphoma 
• 
Follicular T-cell lymphoma 
• 
Nodal peripheral T-cell lymphoma with T-follicular helper phenotype 
• 
Anaplastic large-cell lymphoma, anaplastic lymphoma kinase (ALK)-positive 
• 
Anaplastic large-cell lymphoma, ALK-negative 
• 
Breast implant–associated anaplastic large-cell lymphoma 
The required cut-offs for the CD30-positivity are: 
• 
Cohort A (PTCL): ≥10% by IHC 
• 
Cohort B (PTCL):  ≥1% to <10% by IHC 
• 
Cohort C (TMF):  ≥1% by IHC 
Note: After the planned Interim Analyses, Cohorts A and B may be combined with the 
CD30-positivity defined as ≥1% by centrally assessed IHC. 

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3.6 
Subject Compliance, Lost to Follow-up, and Procedures for Subject 
Discontinuation 
Please refer to Section 6.8 for details of permitted AFM13 dose delays or interruptions. 
A subject 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 certified 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. 
• Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
All 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.  
Per Section 5.1.2, subjects who discontinue treatment due to achieving CR, are still considered to 
be on study and are required to undergo study assessments per the Schedule of Assessments 
 Such subjects may resume treatment where there is subsequent radiological 
evidence of disease progression, following a documented discussion with the Sponsor. 
Upon withdrawal from study drug, the reason for withdrawal should be sought and recorded in 
the subject file and the electronic case report form (eCRF). Every effort will be made to 
complete the Final Study Visit and for the subject to be followed up every 3 months thereafter to 
check for disease progression and survival status. Where a subject withdraws his/her consent to 
participate in the study, such follow-up assessments cannot be conducted. The management and 
holding of data around subject withdrawal will be described in the subject ICF.  
3.7 
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 
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. 

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• Failure of an Investigator(s) to comply with pertinent clinical trial regulations. 
• Submission of knowingly false information from the study site to the Sponsor, clinical 
research associate (CRA), or Competent Authority. 
• 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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4 
STUDY DESIGN 
This is an open-label, multicenter, Phase 2 study in subjects with R/R CD30-positive PTCL or 
TMF to investigate the antitumor activity and safety of AFM13 dosed weekly at 200 mg until 
disease progression, unacceptable toxicity, Investigator discretion or withdrawal of consent.  
Subjects with PTCL or TMF who express CD30 (ie, are confirmed to have ≥1% CD30 
expression) as determined by centrally assessed Ber-H2 targeted IHC (Section 3.1), and who 
meet all of the inclusion criteria and none of the exclusion criteria, will be allowed for this study. 
Subjects with PTCL will be enrolled to Cohort A and Cohort B based on the centrally 
determined CD30 expression levels of ≥10% and ≥1% to <10%, respectively, and subjects with 
TMF will be enrolled to Cohort C based on the centrally determined CD30 expression of ≥1%. 
After the planned Interim Analyses, Cohorts A and B may be combined to include subjects with 
≥1% CD30 expression. The specific subtypes of PTCL allowed for Cohorts A and B are listed in 
the Inclusion Criteria (Section 3.1). A summary of the study design is provided in Figure 2. 
Subjects will receive AFM13 until disease progression, intolerable toxicity, or withdrawal of 
consent. Reasons for withdrawing a subject from the study are described in Section 3.5. 
Figure 2: Study Design 
 
Abbreviations: CD = cluster of differentiation; IHC = immunohistochemistry; PTCL = peripheral T-cell lymphoma; 
R/R = relapsed/refractory; TMF = transformed mycosis fungoides

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5 
STUDY SCHEDULE 
The study consists of a Pre-screening Period, a Screening Period, a Treatment Period, an 
Efficacy and Safety Follow-up Period (Final Study Visit), plus Survival Follow-up. Informed 
consents (one for Pre-screening and a second one for the main study after the confirmation of 
CD30-expression) must be obtained using the current, approved versions of the ICF prior to 
commencing Pre-screening and Screening, respectively. Subjects will undergo a Pre-screening 
for CD30 expression up to 28 days before Screening and, if confirmed, will start Screening 
assessments up to 21 days before receiving the first dose of AFM13. Due to the nature of the 
diseases being studied, Screening assessments may, in practice, be carried out over a shorter 
time-period. The Efficacy and Safety Follow-up Period (Final Study Visit) assessments may be 
conducted between 30 to 37 days after the subject has permanently discontinued AFM13 study 
drug; however, a final AE and concomitant medication review must take place 30 days after the 
last dose of AFM13. Where applicable, disease progression and survival status will be checked 
every 3 months by telephone interview, or during the subject’s routine clinic visits, following 
completion of the Final Study Visit assessments. 
5.1 
Study Periods 
All subjects enrolled may participate in the following study periods: 
• Pre-screening Period   
• Screening Period  
• Treatment Period  
• Efficacy and Safety Follow-up Period (Final Study Visit) 
• Survival Follow-up (after completion of the study) 
Each study period is described below. Subjects will undergo study assessments from the 
Screening Period to the Efficacy and Safety Follow-up Period (Final Study Visit) at scheduled 
site visits as described in the Schedule of Assessments table 
 All subjects are 
considered “on-study” until they complete the Efficacy and Safety Follow-up Period (Final 
Study Visit), withdraw consent, are lost to follow up, or die. 
5.1.1 
Pre-screening and Screening Period 
The study includes a Pre-Screening and a Screening Period. The maximum number of days from 
the time of informed consent for Pre-Screening to the Main study ICF is 28 days.  
During this Pre-Screening Period the subject will be tested for CD30 expression. In addition, the 
ALK status for subjects with systemic ALCL will also be determined.  
The main screening period can last up to 21 days to assess the subject’s full eligibility to move to 
the treatment period of the trial (ie, the subject cannot start dosing until all screening assessments 
confirm the subject’s eligibility). 
Please refer to the guidance document ‘Enrollment process’ for specific details about the 
enrollment process. 

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5.1.2 
Treatment Period 
The Treatment Period will begin following the Screening Period, on Cycle 1 Day 1. Study drug 
will be administered only if the subject meets all inclusion criteria and none of the exclusion 
criteria as defined in Section 3.1 and Section 3.2.  
 
 
 
  
 
 
   
If a subject permanently discontinues study drug, they should continue to the Efficacy and Safety 
Follow-up Period (Final Study Visit). 
5.1.3 
Efficacy and Safety Follow-up Period 
 
 
  
5.1.4 
Follow-up 
 
 
 
 
 
 
5.1.5 
End of Study 
End of study is defined as the point when all subjects have completed their Efficacy and Safety 
Follow-up Period (Final Study Visit) assessments following permanent discontinuation of study 
drug. On completion of the study, data will be reconciled, and the database will be locked for 
analysis. 
5.2 
Schedule of Assessments 
 
 
 
 

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5.4.2 
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 7). 
5.4.3 
Pregnancy and Follicle Stimulating Hormone Tests 
Female subjects of reproductive potential will have a pregnancy test carried out at Screening. 
This test must be carried out within 3 days prior to first AFM13 administration. 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 of reproductive potential with a negative pregnancy test at Screening will 
continue to have pregnancy tests conducted at least every 4 weeks during the study and at the 
Final Study Visit 
 
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.   
5.4.4 
Eastern Cooperative Oncology Group Performance Score 
ECOG Performance Score (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. 
5.4.5 
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.   
5.4.6 
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 AFM13 administration. 

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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.   
5.4.7 
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 Final 
Study 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 
trial. 
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. 
5.4.8 
Electrocardiogram 
A resting 12-lead ECG will be performed at the times given in Schedule of Assessments 
 For those occasions when both an ECG and peripheral blood sample collection 
are required at the EOI of AFM13, the blood draw must be completed first as close to the EOI as 
possible, followed by the ECG. Both procedures should be completed within 10 minutes after the 
EOI (+10 minutes, note plus only).   
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. 
5.4.9 
Disease Assessment 
Imaging assessments, including FDG-PET and CT assessments for Cohorts A and B (PTCL) and 
CT scan or MRI for Cohort C (TMF), will be performed at Screening and every 8 weeks for the 
first 3 assessments, then every 12 weeks thereafter, as well as at the time of suspected clinical 
progression, as described in Schedule of Assessments 
 This scheduling is 
regardless of any treatment/cycle delays that may occur. All imaging assessments will be 

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conducted according to local institutional practice and the same modality should be used for 
initial staging at Screening and all restaging assessments. 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
Further details of the conduct and processing of imaging assessments will be described in the 
Imaging Manual for the study. 
5.4.10 
Response Assessment 
Response assessment will be performed in conjunction with the post dose disease assessments ie, 
every 8 weeks for the first 3 assessments, then every 12 weeks thereafter, as well as at the time 
of suspected clinical progression, as described in Schedule of Assessments 
 
Response assessment will follow the modified Lugano Classification Revised Staging System for 
malignant lymphoma (Cheson, 2014) for subjects with PTCL (Cohorts A and B) and the Olsen 
Criteria (Olsen, 2011) for subjects with TMF (Cohort C) 
  
The modified Lugano Classification refers to the protocol’s separate use of PET-CT based 
response criteria from CT-based response criteria from the Lugano Classification to guide 
clinical decisions and assessment of overall response. The CT-based overall response will be one 
of the secondary endpoints. 
For Cohort C (TMF), the Olsen Criteria determines the global response (GR) based on the 
following: 
• skin assessment by the modified Severity Weighted Assessment Tool (mSWAT) and 
Composite Assessment of Index Lesions Severity (CAILS) 

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• lymph node assessment by CT (or MRI) 
• visceral disease assessment by CT (or MRI) 
• blood assessment by flow cytometry (ie, CD4-positive/CD7-negative and CD4-
positive/CD26-negative subsets) 
 
 
  
Assessments will be performed both locally and centrally, and all imaging scans (PET-CT for 
Cohorts A and B, CT or MRI for Cohort C) will be collected for independent review. Treatment 
decisions should be based on the local disease assessment. 
5.4.11 
Exploratory Biomarkers 
 
 
 
 
 
 
5.4.12 
Cytokines 
All subjects will have blood samples taken to assess cytokine levels at the time points described 
in Schedule of Assessments
 
 
Full details of sample collection and handling of cytokine samples will be described in Lab 
Manual for the study. 
5.4.13 
Anti-drug Antibodies 
All subjects will have blood samples taken to assess for ADA at the time points described in 
Schedule of Assessments 
 
Full details of sample collection and handling of ADA samples will be described in Lab Manual 
for the study. 
5.4.14 
Pharmacokinetic Sampling 
Evaluation of the levels of AFM13 in serum will be performed at the time points described in 
Schedule of Assessments 
 
 

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6 
STUDY MEDICATION AND ADMINISTRATION 
Affimed will supply AFM13 study drug as a sterile lyophilized powder for reconstitution for 
intravenous (IV) infusion (Table 3). Full details on the preparation and administration of AFM13 
are provided in the Pharmacy Manual for the study. 
The Investigator shall take responsibility for the study drug and shall take all steps to maintain 
appropriate records and ensure appropriate supply, storage, handling, distribution, and usage of 
study drug in accordance with the protocol and any applicable laws and regulations. 
The Quality Control Standards and requirements for AFM13 study drug are described in separate 
release protocols/Certificate of Analysis. 
Please refer to the current version of the IB for additional information on the physical, chemical, 
and pharmaceutical properties of AFM13. 
6.1 
Provision and Replacement of AFM13 
Sufficient doses of AFM13 study drug will be supplied. Where study drug supplies (or 
packaging) are apparently damaged on receipt or considered unfit for use by the study site, the 
Sponsor (or their delegate) must be notified immediately. Where required, clinical trial supplies 
will be replaced. Further details on the handling of AFM13 study drug at site will be described in 
the Pharmacy Manual.   

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6.2 
Labelling of AFM13 
AFM13 clinical trial supplies will be labeled in compliance with Good Manufacturing Practice 
Annex 13 requirements, US Food and Drug Administration (FDA) requirements, and any other 
applicable local regulatory guidelines. 
6.3 
Storage of AFM13 
AFM13 study drug 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 (Table 3). 
6.4 
Drug Accountability 
The Investigator is obliged to keep sufficient documentation of the delivery, use and destruction 
or return of unused, used or partially used AFM13 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 AFM13 study drug received for 
the trial. The local CRA will be responsible for checking the drug accountability records 
maintained by the site during study monitoring visits. 
AFM13 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 AFM13 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. 
Certificates of delivery and return must be signed by the responsible pharmacist, 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 AFM13. To help with 
compliance checks, records of usage should include an appropriate form of identification of the 
subject to whom the study drug 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. 

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6.7 
Duration of Treatment 
Treatment with AFM13 should continue until disease progression, unacceptable toxicity, 
Investigator discretion or withdrawal of consent.  
 
 
 
 
 
 
  
6.8 
AFM13 Dose Delays or Interruptions 
The dosing schedule for Study visits that include AFM13 administration permit a tolerance 
window of ±1 day at Cycle 1 Day 8, then a ±3-day tolerance window for all visits thereafter. 
However, the minimum time period between any two consecutive AFM13 administrations 
cannot be less than 3 days.  
AFM13 dosing delays may be permitted in the case of medical/surgical events or logistical 
reasons not related to study therapy (eg, elective surgery, unrelated medical events, subject 
vacation and/or holidays) after obtaining approval from the Sponsor. 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 

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6.9 
Permitted and Restricted Concomitant Medications 
Medications specifically prohibited in the exclusion criteria (Section 3.2) are not allowed during 
the ongoing trial. If there is a clinical indication for any medication specifically prohibited during 
the trial, discontinuation from trial therapy may be required. The final decision on any supportive 
therapy rests with the Investigator and/or the subject's primary physician. However, in such 
cases, the decision to continue the subject on AFM13 study drug requires the mutual agreement 
of the Investigator, Sponsor and the subject. 
6.9.1 
Acceptable Concomitant Medications 
All treatments and supportive care that the Investigator considers necessary for a subject’s 
welfare may be administered at the discretion of the Investigator in keeping with the study site’s 
standards of medical care except for the prohibited concomitant medications listed in 
Section 6.9.2. All concomitant medication will be recorded in the eCRF including all 
prescription, over-the-counter, herbal supplements, and iv medications and fluids. If changes 
occur during the trial period, documentation of drug dosage, frequency, route, and date may also 
be included in the eCRF. All concomitant medications received within 30 days before the first 
dose of study drug and 30 days after the last dose of study drug should be recorded. Concomitant 
medications administered >30 days after the last dose of study drug should be recorded for 
serious adverse events (SAEs) that are considered related to study drug (Section 7.10). 
6.9.1.1 
Highly Effective Contraception 
Both sexually active females of childbearing potential and non-vasectomized male subjects with 
female partners of childbearing potential are required to use highly effective methods of 
contraception, initiated prior to first dose of study drug, continued during study drug, and for at 
least 60 days after the last dose of study drug. Note that for non-vasectomized male subjects, 
some of these methods are applicable to their female partners. 
Highly effective methods of contraception, including abstinence, are defined as follows: 
• Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with the inhibition of ovulation; may be oral, intravaginal or transdermal method; 
• Progestogen-only hormonal contraception associated with the inhibition of ovulation; 
may be oral, injectable, implantable method; 
• An intrauterine device; 
• Intrauterine hormone-releasing system; 
• Bilateral tubal occlusion; 
• Vasectomized partner of a female subject (provided that the vasectomized partner is the 
sole sexual partner of the woman of childbearing potential study subject and that the 
vasectomized partner has received medical assessment of surgical success); or 
• Sexual abstinence (defined as refraining from heterosexual intercourse during the entire 
period of risk associated with the study drug, starting prior to first dose of study drug, for 
the duration of study drug, and for at least 60 days after the last dose of study drug. Total 
sexual abstinence should only be used as a contraceptive method if it is in line with a 

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7 
ADVERSE EVENTS AND REPORTING REQUIREMENTS 
7.1 
Assessment of Safety 
All subjects who receive treatment with AFM13 will be considered evaluable for safety. All AEs 
and SAEs will be collected from the time the subject gives informed consent up to and including 
 There will be a baseline medical condition review 
taken at Screening. AEs, other than the primary disease under evaluation, that worsen in severity 
or frequency from this baseline assessment during the study, should be recorded and reported as 
AEs.   
In addition, as part of the documentation of an AE in the electronic documentation system, sites 
will be asked to identify whether the event is related to an infusion-related reaction. 
If the Investigator detects an SAE in a study subject after the end of the period of observation 
and considers the event possibly related to prior study drug or procedures, they should contact 
the Sponsor to determine how this event should be documented and reported. 
7.2 
Adverse Event Definition 
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, for example), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not considered related to AFM13. 
During clinical trials, 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. AEs include: 
• Worsening (change in nature, severity, or frequency) of conditions present at the start of 
the study;  
• Intercurrent illness;  
• Drug interactions;  
• Experiences related or possibly related to concomitant medications;  
• Clinically significant abnormal laboratory values or shifts from baseline; and  
• Clinically significant abnormalities in physical examination, vital signs, weight or ECG. 
Symptoms and signs of exacerbation or worsening of the subject’s primary disease will not be 
captured as AEs. Progression of the disease under study will not be captured as an AE unless it is 
considered to be drug-related by the Investigator. 
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. 
7.3 
Importance of Adverse Event 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 trial conduct. 
7.4 
Evaluating Adverse Events 
Following the subject’s written consent to participate in the study, all AEs should be collected. 
All identified AEs must be recorded and described on the appropriate AE page of the eCRF, 
except for those events occurring prior to the first dose of study drug, which should be recorded 
on the Medical History eCRF page. 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 (see definitions in Section 7.5), assessment whether the event was serious or 
non-serious, Investigator's opinion of the relationship to AFM13 (see definitions in Section 7.8) 
treatment required for the AE, action taken with AFM13 study drug and information regarding 
resolution/outcome. 
7.5 
Severity 
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 (or higher) 
 For events not addressed in the NCI CTCAE v5.0 classifications, 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 noninvasive 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. 

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7.6 
Serious Adverse Events 
An SAE is defined as any untoward medical occurrence that at any dose causes or qualifies as 
the following: 
• Results in death. 
• Is life-threatening: 
o “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: 
o 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. 
o 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. 
Note: Preventive hospitalization due to current COVID-19 pandemic (eg, to 
minimize exposure to COVID-19) will not be categorized as SAE. 
• Results in persistent or significant disability or incapacity: 
o “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. 
• Is an important medical event: 
o Medical and scientific judgment should be exercised in deciding whether expedited 
reporting is appropriate in situations where none of the outcomes listed above 
occurred. Important medical events that may not be immediately life-threatening or 
result in death or hospitalization but may jeopardize the subject or may require 
intervention to prevent one of the other outcomes listed in the definition above should 
also usually be considered serious. Examples of such events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias, or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse. 
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.  
7.7 
Other Important Events for Immediate Reporting 
AEs meeting the below criteria, although not categorized as ‘Serious’ per ICH definition, are 
reportable to the Sponsor in the same timeframe as SAEs to meet certain local requirements and 
the study needs: 
• A new cancer (that is not a condition of the study); 
• A reported pregnancy or lactation after receipt of study drug and for ≤60 days from last 
dose; 

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• An overdose (defined as any dose of AFM13 which more than the assigned dose for that 
subject is). 
• 
Any confirmed or suspected COVID-19 infection (eg, in case the subject cannot be tested 
due to lock-down) should be reported as Important Medical Event, regardless of the 
hospitalization status or severity of the event; as this is an adverse event that may 
jeopardize the subject safety or may require intervention to prevent a severe, life 
threatening or fatal outcome. Note: Continuation in the study should be assessed by the 
Investigator and according to the protocol criteria for study termination. Dose delay vs. 
study termination should be driven by the overall health status of the subject, and the 
safety of the subject shall prevail at all times. 
Such events must be reported within 24 hours to the Sponsor by means of an SAE form either by 
electronic report or paper.  
7.7.1 
Exposure During Pregnancy or Lactation 
Although pregnancy and lactation are not considered AEs, it is the responsibility of Investigators 
or their designees to report any pregnancy or lactation in a subject (spontaneously reported to 
them) or pregnancy in a subject’s partner that occurs during the trial. 
Pregnancies and lactations that occur in subjects after the ICF is signed but before starting study 
drug must be reported by the Investigator if they cause the subject to be excluded from the trial. 
Pregnancies and lactations that occur in a study subject or a pregnancy in a subject’s partner 
from the time of first study drug through to 60 days following cessation of AFM13 study drug, 
must be reported by the Investigator. All reported pregnancies must be followed to the 
completion or termination of the pregnancy. If the pregnancy continues to term, the outcome ie, 
the health of the infant, will be requested by the Sponsor. 
Such events must be reported within 24 hours to the Sponsor via email, fax, or telephone. The 
reporting procedures can be found in the SAE completion guidelines located in the Study 
Operations Manual (or equivalent). 
7.7.2 
Misuse and Overdose 
Study drug misuse or overdose should be reported in the same format and within the same 
timelines as an SAE, even if they may not result in an adverse outcome. In the event of overdose, 
the subject should be observed closely for signs of toxicity. Appropriate supportive treatment 
should be provided if clinically indicated. 
For the purpose of this protocol, an overdose is any dose of AFM13 which is more than the 
assigned dose level for that subject. 
If the pharmacy discovers that an overdose has or may have been administered, they should 
contact the Investigator and Sponsor (or their delegate) immediately. 

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7.7.3 
Investigational Product Complaints 
Pharmaceutical technical complaints associated with the investigational product must be reported 
to the Sponsor immediately, following the guidance specified in the Pharmacy Manual. The 
same reporting timelines as for SAEs will apply.  
7.8 
Relationship 
All AEs (including SAEs) will be assessed for the relationship of the AE to the study drug using 
the following definitions: 
• Not/unlikely related - The AE is not related if exposure to the investigational product 
has not occurred, OR the occurrence of the AE is not reasonably related in time, OR the 
AE is considered unlikely to be related to use of the investigational product because there 
are no facts (evidence) or arguments to suggest a causal relationship AND there is a 
possible alternative explanation.  
• Possibly related - The administration of the investigational product and AE are 
considered reasonably related in time AND the AE could be explained by causes other 
than exposure to the investigational product. 
• Probably related - Exposure to the investigational product and AE are reasonably related 
in time AND the investigational product is more likely than other causes to be responsible 
for the AE OR is the most likely cause of the AE. 
• Definitely related - There is a reasonable temporal sequence between exposure to the 
investigational product and the AE, OR the event follows a known or expected response 
pattern to the investigational product AND is confirmed by improvement on stopping the 
dosage of the investigational product. It may also be confirmed by reappearance upon 
repeated exposure where this is medically and ethically acceptable. 
Please also refer to supporting information provided in
 The relationship of the study 
drug to an AE will be determined by the Investigator and subsequently reviewed by the Sponsor. 
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. 
7.9 
Unexpected Adverse Events 
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 consistent with those 
noted in the current IB section Reference Safety Information. 
7.10 
Reporting Serious Adverse Events 
Adverse Events classified as serious require expeditious handling and reporting to the assigned 
Drug Safety contact to comply with regulatory requirements.  
Any SAE that occurs while a subject is on study ie, occurs within 30 days of the last study drug 
administration, regardless of any opinion as to the relationship of the SAE to the study drug, 

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7.12 
Follow Up Information on an SAE 
Collection of complete information concerning SAEs is extremely important. Thus, follow-up 
information that becomes available as the SAE evolves, as well as supporting documentation (eg, 
hospital discharge summaries and autopsy reports), should be collected subsequently, if not 
available at the time of the initial report, and immediately sent using the same procedure as the 
initial SAE report. The original SAE form must be kept on file at the study site. The Sponsor (or 
their delegate) will also review SAE reports for missing information and send queries to the site 
for resolution as appropriate. 
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). An SAE is followed until it is considered resolved, returns to baseline, 
is chronically ongoing, stabilized or is otherwise explained by the Investigator.  
 

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8 
STATISTICAL METHODS AND DATA ANALYSIS 
Detailed statistical analysis information will be provided separately in the Statistical Analysis 
Plan (SAP) which will be finalized and signed before the database is locked. The SAP will detail 
all data handling rules, including the management of missing values and the handling of data for 
withdrawn subjects. The SAP 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 (ie, “cleaned”) for all subjects 
who receive at least one dose of AFM13. 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. 
Where appropriate, tables, listings and figures will be reported by Cohort. Data may be 
combined and/or summarized by cohort, dose (if different from cohort) and time point.  
8.1 
Analysis Sets 
The study will have three separate cohorts: first cohort (Cohort A) with R/R PTCL subjects with 
CD30 ≥10%, second cohort (Cohort B) with R/R PTCL subjects with CD30 ≥1% to <10%, and 
the third cohort (Cohort C) with R/R TMF subjects with CD30 ≥1%. All three cohorts will be 
analyzed independently as described below. 
The full analysis set (FAS) following the intent to treat (ITT) principle will consist of all 
subjects who received at least one dose of AFM13. The FAS will be the primary population for 
all efficacy related endpoints and the primary objective; a sensitivity analysis for all subjects who 
received at least one dose of AFM13 and had at least one post-baseline efficacy assessment will 
be conducted to support the results of the primary analysis. 
The safety set will consist of all subjects who received at least one dose of AFM13 and had at 
least one post-baseline safety assessment (where the statement that a subject had no AE on the 
AE eCRF constitutes a safety assessment). The safety set will be the primary population for all 
safety related endpoints. 
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 pharmacokinetic set (PK) set consists of all subjects who have at least received one dose of 
study drug and have at least one post dose PK measurement. 
Additional sensitivity analyses might be needed due to the COVID-19 pandemic and those will 
be defined in the SAP, if deemed necessary. 
Subjects who were screened and have signed the ICF but did not receive any treatment will be 
listed including reason for screen failure and any SAE (this will be recorded in the medical 

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history). These subjects will not be part of any summary table except for summarizing 
disposition. 
8.1.1 
Missing Data and Discontinuation 
As this is a non-randomized study design, no imputation of missing values will be done for any 
analysis except for partial/missing AE dates and concomitant medication dates. Reasons for 
discontinuation of the study and the study drug will be listed and summarized. 
Subjects with missing post-baseline response will be classified as non-responders; however, due 
to the COVID-19 pandemic additional analyses might be needed and will be specified in the 
SAP (see Section 2.1). 
8.2 
Demographic, Medical History, Prior Medication and Other Baseline 
Characteristics 
Demographic 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 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. 
8.3 
Study Drug 
The number of doses of AFM13 administered over the entire study period will be listed and 
summarized using descriptive statistics. The time on study drug until last treatment received will 
be listed and presented by descriptive statistics.   
8.4 
Concomitant Medication 
Concomitant medication and significant non-drug therapies after the start of study drug will be 
listed and summarized by WHO ATC terms in contingency tables. 
8.5 
Primary Analysis 
8.5.1 
Overall Response Rate 
Overall response by PET-CT as defined by achieving CR and/or PR assessed by an Independent 
Review Committee (IRC) utilizing the modified Lugano Classification Revised Staging System 
for malignant lymphoma (Cheson, 2014) for Cohorts A and B (PTCL) and the Olsen Criteria 
(Olsen, 2011) for Cohort C (TMF). Subjects with missing post-baseline response will be 
classified as non-responders in the FAS. Results will be presented by percentage rates and 95% 
CIs. In addition, CR and PR will be presented separately. For all response assessments, swimmer 
plots will be presented. All response assessments will be listed. 
Cohorts A and Cohort C will be analyzed separately and independent from each other at the final 
analysis. Cohort A may be opened after the interim analysis for all PTCL subjects with 
CD30 ≥1%, if Cohort B showed the required ORR (see Section 8.8.1). The final analysis for 

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Cohort A will be conducted once all subjects have completed at least two post-baseline disease 
assessments (ie, ~ 16 weeks post-baseline assessment) to be categorized under the response 
endpoint or have withdrawn from study drug. 
8.6 
Secondary Analysis 
8.6.1 
Efficacy Analyses 
Efficacy analyses will be performed based on IRC assessment and Investigator assessment of 
disease response. 
8.6.1.1 
Investigator-assessed ORR 
The primary analysis will be repeated using the local Investigator-assessed ORR. 
8.6.1.2 
Duration of Response 
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 
(PD) 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. 
8.6.2 
Safety Analysis 
8.6.2.1 
Adverse Events 
Adverse events, related AEs, SAEs and related SAEs, AEs with NCI CTCAE Grades ≥3, related 
AEs of NCI CTCAE Grades ≥3, AEs leading to premature discontinuation, interruptions or 
discontinuation of study drug or dose modification will be analyzed descriptively utilizing 
corresponding MedDRA SOCs and PTs. NCI CTCAE toxicity grades will be utilized for 
classifying severity. 
8.6.2.2 
Safety Laboratory 
Safety laboratory results will be graded by NCI CTCAE version v5.0 (or higher). If no grading 
exists values will be classified into low/normal/high based on laboratory normal ranges. Each 
parameter will be presented by descriptive statistics at each visit including change from baseline 
(Screening). Shift tables for CTCAE grades and normal ranges will be presented. All laboratory 
values will be listed. A separate listing for abnormal lab values (≥Grade 3, and low/high values) 
will be presented. 
8.6.2.3 
Vital Signs 
Vital signs will be summarized by descriptive statistics at each visit including change from 
baseline will be presented and a listing will be provided. 

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9 
QUALITY ASSURANCE 
9.1 
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, 
and 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. 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 assure that subject confidentiality is maintained. 
All eCRF data will be collected using an eCRF within a fully validated and CFR 21 Part 11-
compliant electronic data capture 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 electronic data 
capture 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 version of 
SAS® and WinNonLin Pro, or equivalent. 
9.2 
Study Monitoring 
CRAs 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 collections. 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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9.3 
Clinical Study Audit 
The Sponsor, Sponsor representative, or external regulatory agency may at any time during or 
after completion of the study conduct a Good Clinical Practice (GCP) audit. Prior notice will be 
given to each site selected for audit in advance of a planned audit. 
9.4 
Clinical Study Report 
The results of the study will be presented in an integrated CSR according to ICH guidelines. 
9.5 
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 12.2 for details of required record retention for the study. 
9.6 
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. 
9.7 
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 trial 
subjects, or when the change involves only logistical or administrative aspects of the trial (eg, 
change in monitor, change in telephone number). Other administrative revisions which may 
impact the clinical portion of a study will be duly reported to the IRB/EC by the Principal 
Investigator. 
 

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10 
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 trial will be documented as amendments. Depending on the 
contents of the amendment 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 trial 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 trial, 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 trial procedures and is affected by the amendment, then the subject must 
be asked to consent again using the new ICF. 
10.1 
Ethical Conduct of the Study 
The study will be conducted in accordance with ICH GCP, the Declaration of Helsinki, the 
European Union  Clinical Trials Directive 2001/20/EC, the GCP Directive 2005/28/EC, the 
requirements of local IRB/EC, and the US Code of Federal Regulations, Title 21 CFR Part 50.  
10.2 
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 AFM13 study drug and 
anticipated effects and the reason, design and implication of the trial. The subject must give 
consent to participate prior to enrolment in the trial. 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 (eg, 
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 

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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. 
The signed and dated consent form will be kept by the Investigator. Prior to participation in the 
trial, 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 trial.  
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. 
10.3 
Patient 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 trial 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 trial 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. A sample patient participation card is shown below. 
Figure 3: Sample Patient Participation Card 
 
Dear Patient,  
 
Please inform any physician you visit during 
the course of the study that you are 
participating in a clinical trial by presenting 
this contact card. 
 
Please carry this card with you at all times until 
the end of the study. 
 
Patient Name:................................................. 
is participating in an open-label trial and is 
receiving an investigational product, AFM13, 
a novel, tetravalent bispecific chimeric (anti-
human 
CD30 
x 
anti-human 
CD16A) 
recombinant antibody construct (ROCK®). 
 
 
 
Patient Contact Card Version X/date 
 
 
Clinical Trial Contact Card 
Study AFM13-202: A Phase II Open-label 
Multicenter Study to Assess the Efficacy and 
Safety of AFM13 in Patients with Relapsed or 
Refractory CD30-positive Peripheral T-cell 
Lymphoma or Transformed Mycosis Fungoides 
 
In the case that additional medications must be 
prescribed, you need more information about 
the clinical trial, or the patient’s condition has 
worsened, please contact the treating study 
physician: 
 
Name: ..................................................................
 
Phone: ..................................................................
 
Address: 
…………………………………………... 
 

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10.4 
Insurance 
Appropriate insurance for this trial will be arranged by Affimed (or their delegate), as Sponsor of 
the clinical trial, 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 and in the 
Investigator Site File. 
10.5 
Institutional Review Board/Independent Ethics Committee 
The study will not be initiated without 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.  
10.6 
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 (eg, 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 
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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11 
DATA CONFIDENTIALITY AND PUBLICATION POLICY 
The original CRFs and all data generated during the clinical study are the property of the 
Sponsor. In addition, all information regarding AFM13 and the Sponsor’s operations (eg, patent 
applications, formulas, manufacturing processes, basic scientific data or formulation 
information) supplied by the Sponsor to the Investigator and not previously published is 
considered confidential. This confidential information remains the sole property of the Sponsor 
and shall not be disclosed to others without the written consent of the Sponsor. The Investigator 
agrees to use this information only to perform this study and will not use it for other purposes, 
including publications and presentations, without the Sponsor’s written consent. 
The first publication of the study results shall be made by the Sponsor. Any proposed publication 
or presentation (including a manuscript, abstract or poster) for submission to a journal or 
scientific meeting should be sent to the Sponsor for review prior to submission. Publication of 
the results will not include confidential information, including inventions, non-public intellectual 
property rights and know how, without the permission of the Sponsor. The full terms of 
confidentiality, intellectual property and publication policy are described in the current Clinical 
Trial Agreement between the Sponsor and the site. 
The Sponsor may announce quality assured summary data to comply with Financial Regulatory 
Authorities, while ensuring, so far as possible, that such announcements will not compromise the 
Investigators ability to publish the data in appropriate scientific forums. 
 

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12 
DATA HANDLING AND RECORD KEEPING 
12.1 
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. 
12.2 
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 (ie, 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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