Clinical trial NCT04101331
Conditions: Peripheral T Cell Lymphoma Transformed Mycosis Fungoides
Sponsor: Affimed GmbH
Start date: 2019-11-13; Completion date: 2024-01-11
Enrollment: 108 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a phase II study to evaluate the antitumor activity and safety of AFM13 given as monotherapy in patients with CD30-positive T-cell lymphoma. The investigational medicinal product AFM13 is a tetravalent bispecific chimeric (anti-human CD30 x anti-human CD16A) recombinant antibody construct which is being developed to treat CD30-positive malignancies.

Patients who suffer from peripheral T-cell lymphoma or transformed mycosis fungoides, whose tumor expresses the surface marker CD30, and who have relapsed after an earlier treatment or have refractory disease will be enrolled into this study if all of the study entry criteria are fulfilled. Dependent on their disease type and the magnitude of CD30 expression, study participants will be assigned to one of 3 study cohorts, each cohort receiving the same treatment of weekly AFM13 infusions (a 200mg dose per infusion).

The main goal of the study is to assess the efficacy of AFM13 treatment as judged by the rate of overall responses. Further goals are to assess the safety of AFM13 treatment, the immunogenicity of AFM13 (as measured by the potential formation of anti-AFM13 antibodies) and the concentration of AFM13 in the blood.

Approx. 1 month after the last dose of AFM13 there will be a final study visit to assess the patients' health status after therapy, followed by quarterly phone contacts to check on their overall health status and long-term survival.

Detailed description:

Arms: arm 1: Subjects with Relapsed or Refractory CD30 positive Peripheral T-cell Lymphoma (PTCL).
Interventions: intervention 1: AFM13
Intervention descriptions: intervention 1: weekly intravenous infusions of 200mg

Protocol documents:
Prot_002.pdf: 
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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 
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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 
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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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SAP_001.pdf: 
 
 
Final Analysis 
Statistical Analysis Plan (SAP) 
 
Statistical Analysis Plan 
Protocol Number: AFM13-202 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019                   
               Version: FINAL 3.0, Date: 13 Sep 2022
                                                               Page 1 of 48
(Ref. BST004-SOP) 
 
 
Protocol 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) 
 
Protocol Number: 
AFM13-202 
Protocol Version, Date 
V6.0, 12 July 2021 
ICON ID:  
3499/0003 
Document Version, Date: 
Final 3.0, 13 September 2022  
 
Prepared by: 
ICON Clinical Research Services 
 
On behalf of: 
Affimed GmbH 
 
 
Confidentiality statement: 
 
The information provided in this document is strictly confidential.  
 
The recipients of the SAP must not disclose the confidential information contained 
within this document or any related information to other persons without the 
permission of the sponsor. 
 
In addition, the recipients of the SAP must keep this confidential document in a 
controlled environment, which prevents unauthorized access to the document. 
 
 
 


 
 
Final Analysis 
Statistical Analysis Plan (SAP) 
 
Statistical Analysis Plan 
Protocol Number: AFM13-202 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019                   
               Version: FINAL 3.0, Date: 13 Sep 2022
                                                               Page 2 of 48
(Ref. BST004-SOP) 
 
SIGNATURE PAGE 
 
 
Prepared at ICON Clinical Research by:  
 
 
 
 
 
 
, Senior Statistician I 
 
Date  
(DDMMMYYYY) 
 
 
Reviewed at ICON Clinical Research by:  
 
 
 
 
 
 
 
 
, Principal Biostatistician 
 
Date  
(DDMMMYYYY) 
 
 
 
 
 
Approved at Affimed GmbH by: 
 
 
 
 
 
 
 
 Senior Statistician 
 
Date  
(DDMMMYYYY) 
 
 
 
 
 
 
 
 Senior Director Data Sciences 
 
Date  
(DDMMMYYYY) 
 


 
 
Final Analysis 
Statistical Analysis Plan (SAP) 
 
Statistical Analysis Plan 
Protocol Number: AFM13-202 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019                   
               Version: FINAL 3.0, Date: 13 Sep 2022
                                                               Page 3 of 48
(Ref. BST004-SOP) 
 
REVISION HISTORY 
 
 
 
 
 
 
 
Version 
Date 
Section 
Changes implemented 
1.0 
09JAN2020 
N/A 
Initial version 
2.0 
01SEP2020 
 
- Addition of subgroups for overall 
response rate and duration of 
response. 
- Addition of new parameters and 
analyses due to COVID-19. 
- Addition of new parameters and 
analyses due to protocol amendment 
dated 02-Jul-2020. 
3.0 
13SEP2022 
 
- Clarification on the category names 
for premedications. 
- Replace “Most frequent TEAEs” by 
“Most frequent non-serious TEAEs”. 
- Addition of COVID-19 vaccination. 
- Integration of protocol amendment 
dated 29-Jun-2021. 
- Modification of Tables 2 and 4. 
- Modification of section 7.1. 
- Modification of section 7.2.2. 
- Modification of section 8.7.3. 
- Modification of section 8.6.2. 
- Modification of section 8.8.1. 
- Modification of section 8.8.5. 
- Modification of section 9. 


 
 
Final Analysis 
Statistical Analysis Plan (SAP) 
 
 
Statistical Analysis Plan 
Protocol Number: AFM13-202 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019                   
               Version: FINAL 3.0, Date: 13 Sep 2022
Page 4 of 48
(Ref. BST004-SOP) 
 
TABLE OF CONTENTS 
 
REVISION HISTORY.................................................................................................................... 3 
TABLE OF CONTENTS ................................................................................................................ 4 
LIST OF ABBREVIATIONS ......................................................................................................... 6 
1 INTRODUCTION .................................................................................................................... 8 
2 STUDY OBJECTIVES ............................................................................................................. 9 
2.1 Primary objective ............................................................................................................. 9 
2.2 Secondary objectives ....................................................................................................... 9 
2.3 Exploratory objectives ..................................................................................................... 9 
2.4 Safety objective ................................................................................................................ 9 
3 STUDY DESIGN .................................................................................................................... 10 
3.1 General study design ...................................................................................................... 10 
3.2 Randomization and blinding .......................................................................................... 11 
3.3 Study treatments and assessments ................................................................................. 11 
4 STUDY ENDPOINTS ............................................................................................................ 12 
4.1 Primary efficacy endpoint .............................................................................................. 12 
4.2 Secondary efficacy endpoints ........................................................................................ 12 
4.3 Exploratory endpoints .................................................................................................... 12 
4.4 Safety endpoints ............................................................................................................. 13 
5 SAMPLE SIZE AND POWER ............................................................................................... 14 
6 ANALYSIS POPULATIONS ................................................................................................ 15 
6.1 Full analysis set (FAS) ................................................................................................... 15 
6.2 COVID analysis set........................................................................................................ 15 
6.3 Safety set (Safety) .......................................................................................................... 15 
6.4 Per protocol set (PP) ...................................................................................................... 15 
6.5 Pharmacokinetic set (PK) .............................................................................................. 15 
6.6 Protocol deviations and exclusions from analysis sets .................................................. 15 
7 Statistical considerations and analysis .................................................................................... 17 
7.1 Derived variables ........................................................................................................... 17 
7.2 Handling of missing data and outliers ........................................................................... 18 
7.2.1 Missing data analysis methods........................................................................... 18 
7.2.2 Handling of missing or incomplete dates........................................................... 18 
7.3 COVID-19 parameters definitions ................................................................................. 20 
8 STATISTICAL METHODS ................................................................................................... 21 
8.1 General statistical conventions ...................................................................................... 21 
8.2 Subject disposition ......................................................................................................... 22 
8.3 Protocol deviations......................................................................................................... 22 
8.4 Demographics and baseline characteristics ................................................................... 22 
8.4.1 Demographics .................................................................................................... 22 


 
 
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8.4.2 Baseline and disease characteristics ................................................................... 23 
8.4.3 Medical history .................................................................................................. 24 
8.4.4 Prior and concomitant medications .................................................................... 24 
8.4.5 Prior anti-cancer medications ............................................................................ 25 
8.5 Exposure to study treatment........................................................................................... 25 
8.5.1 AFM13 study drug ................................................................................................ 25 
8.5.2 Premedications ...................................................................................................... 26 
8.6 Efficacy analyses ........................................................................................................... 27 
8.6.1 Analysis methods ............................................................................................... 27 
8.6.1.1 Multiplicity ........................................................................................................ 27 
8.6.1.2 Treatment by center interaction analysis (multi-center study) .......................... 27 
8.6.1.3 Overall response date of assessment .................................................................. 27 
8.6.1.4 Derivation of post-baseline disease assessments visits ...................................... 27 
8.6.2 Analysis of efficacy endpoints ........................................................................... 27 
8.6.3 Analysis of exploratory endpoints ..................................................................... 35 
8.7 Safety analyses ............................................................................................................... 36 
8.7.1 Adverse events ................................................................................................... 36 
8.7.2 Clinical laboratory evaluations .......................................................................... 38 
8.7.3 Cytokines ........................................................................................................... 39 
8.7.4 Vital signs .......................................................................................................... 39 
8.7.5 Physical examinations ........................................................................................ 39 
8.7.6 Electrocardiograms ............................................................................................ 40 
8.7.7 ECOG performance status ................................................................................. 40 
8.8 Other analysis................................................................................................................. 40 
8.8.1 Statistical analysis for PK data .......................................................................... 40 
8.8.2 Immunogenicity analyses................................................................................... 40 
8.8.3 Quality of life analyses ...................................................................................... 41 
8.8.4 Biomarker analysis............................................................................................. 42 
8.8.5 Subgroup analysis .............................................................................................. 42 
8.9 Interim analysis .............................................................................................................. 43 
9 CHANGES TO PLANNED ANALYSIS FROM STUDY PROTOCOL .............................. 44 
10 REFERENCES ....................................................................................................................... 45 
11 APPENDIX A ......................................................................................................................... 46 
 
 


 
 
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LIST OF ABBREVIATIONS 
The following abbreviations will be used within this SAP: 
 
Abbreviation 
or special term 
Explanation 
ADA 
anti-drug antibodies 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine transaminase 
AST 
aspartate transaminase 
ATC 
Anatomical, Therapeutic and Chemical 
AUC 
area under the concentration versus time curve 
BLQ 
Below limit of quantification 
BMI 
body mass index 
BOR 
best overall response 
CAILS 
Composite Assessment of Index Lesions Severity 
CI 
confidence interval 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CL 
clearance 
Cmax 
maximum concentration 
CR 
complete response/remission 
CRP 
C-reactive protein 
CSR 
clinical study report 
CT 
computed tomography 
CTCAE 
common terminology criteria for adverse events 
CV 
Coefficient of variation 
DOR 
duration of response         
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group                 
eCRF 
electronic Case Report Form 
EQ-5D 
European Quality of Life 5-Dimensional 
FAS 
full analysis set 
FDG 
fluorodeoxyglucose 
ICF 
informed consent form 
ICH 
International Council for Harmonization 
IME 
important medical event 
IRC 
Independent Review Committee 
IRR 
infusion-related reaction 


 
 
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ITT 
intent to treat 
LDH 
lactate dehydrogenase 
LLN 
lower limit of normal 
LLOQ 
lower limit of quantitation 
MedDRA 
Medical Dictionary for Regulatory Activities 
mSWAT 
modified Severity Weighted Assessment Tool 
NCA 
non-compartmental analysis 
NSAID 
nonsteroidal anti-inflammatory drug 
ORR 
overall (or objective) response rate 
OS 
overall survival 
PD 
progressive disease 
PET 
positron emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PR 
partial response/remission 
PT 
preferred term 
PTCL 
peripheral T-cell lymphoma 
Q2W 
every other week 
QOL 
quality of life 
QTc 
corrected Q wave to T wave interval 
R/R 
relapse or refractory 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
stable disease 
SDTM 
Study Data Tabulation Model 
SMQ 
Standardized MedDRA Queries 
SOC 
system organ class 
t1/2 
half-life 
TEAE 
treatment-emergent adverse event 
TFL 
tables, figures, listings 
TMF 
transformed mycosis fungoides 
TNMB 
primary tumor/lymph nodes/metastasis/tumor burden 
ULN 
upper limit of normal 
ULOQ 
upper limit of quantitation 
Vss 
volume of distribution at steady state 
WBC 
white blood cells 
WHO 
World Health Organization 
WHODDE 
WHO Drug Dictionary Enhanced 


 
 
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1 
INTRODUCTION 
The purpose of this Statistical Analysis Plan (SAP) is to provide detailed descriptions of the statistical 
methods, data derivations and data displays for study protocol AFM13-202 Version 6.0 “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)” 
dated 12 July 2021 for interim and final analyses. The table of contents and templates for the TFLs will be 
produced in a separate document. 
Any deviations from this SAP will be described and justified in the Clinical Study Report (CSR). 
The preparation of this SAP has been based on International Conference on Harmonization (ICH) E9 and 
E3 guidelines. 
All data analyses and generation of TFLs will be performed using SAS 9.4® or higher. 
 
 


 
 
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2 
STUDY OBJECTIVES 
2.1 
Primary objective 
 
To assess the antitumor activity of AFM13 by an Independent Review Committee (IRC) 
confirmed -PET-CT based overall response rate (ORR). 
2.2 
Secondary objectives 
The secondary objectives of this study are as follows: 
 
To assess the antitumor activity of AFM13 by IRC-confirmed complete response (CR) and 
partial response (PR) rates and computed tomography (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. 
 
To assess the immunogenicity of AFM13. 
 
To assess the Quality of Life (QOL) of subjects while on treatment with AFM13. 
2.3 
Exploratory objectives 
 
 
 
 
 
 
 
 
 
 
2.4 
Safety objective 
Not applicable. 


 
 
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3 
STUDY DESIGN  
3.1 
General study design 
This is an open-label, multicenter, Phase 2 study in subjects with R/R CD30-positive PTCL and TMF.  
Subjects with PTCL will be enrolled to Cohort A or B based on the centrally determined CD30 expression 
level detailed below: 
 
Subjects with ≥10% CD30 expression for Cohort A 
 
Subjects with ≥1% to <10% CD30 expression for Cohort B 
After the planned Interim Analysis (IA), Cohorts A and B may be combined with the CD30 positivity 
defined as ≥1% by centrally assessed IHC. 
Subjects with TMF and centrally determined ≥1% CD30 expression will be enrolled to Cohort C.  
The study targets 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. 
The Study Flow Chart is presented in Figure 1. 
Figure 1: Study Flow Chart 
 
Abbreviations: CD = cluster of differentiation; IHC = immunohistochemistry; PTCL = peripheral T-cell lymphoma;  
R/R = relapsed/refractory; TMF = transformed mycosis fungoides.


 
 
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All subjects enrolled may participate in the following study periods: 
 
Pre-screening period (up to 28 days prior to starting the screening period). 
 
Screening period (up to 21 days prior to first dose of AFM13). 
 
Treatment period. 
 
Efficacy and Safety follow-up period (30 to 37 days from last dose of AFM13). 
 
Survival follow-up (after completion of the study) every three months after Final study visit 
(+/- 1 month). 
Subjects will undergo study assessments from the Screening period to the Efficacy and Safety follow-up 
period at scheduled site visits. All subjects are considered “on study” until they complete the Efficacy and 
Safety follow-up period, withdraw consent, are lost to follow up, or die. 
A subject is considered to have completed the study if the subject has either a disease progression or died or 
completed the Efficacy and Safety follow-up or when the subject has at least a partial response/remission and 
gets transitioned to a transplant. 
3.2 
Randomization and blinding 
Not applicable. 
3.3 
Study treatments and assessments 
AFM13 will be administered intravenously 
 
 Subjects   will   be   treated   weekly   until   disease   
progression, unacceptable toxicity, Investigator discretion, or withdrawal of consent. After 16 weeks (from 
Cycle 2 Day 50 onwards), subjects who are experiencing persistent infusion-related reactions (IRRs) and have 
achieved an objective response (at least PR) may be dosed on an every other week schedule (Q2W), at the 
discretion of the Investigator, until disease progression, unacceptable toxicity, Investigator discretion or 
withdrawal of consent.  
A detailed description of procedures and assessments to be conducted during this study is presented in 
Appendix A of the protocol. A cycle in the study is defined as an 8-weeks period. 


 
 
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4 
STUDY ENDPOINTS 
4.1 
Primary efficacy endpoint 
The primary efficacy endpoint of this study is: 
 
ORR (CR + PR) as confirmed by an IRC as assessed by the modified Lugano Classification (Cheson, 
2014) for Cohorts A and B (PTCL) based on PET-CT and after at least 8 weeks from the first 
assessment as assessed by Olsen Criteria (Olsen, 2011) for Cohort C (TMF).  
4.2 
Secondary efficacy endpoints 
The secondary efficacy endpoints of this study are: 
 
CR rate, PR rate, and CT-based ORR as confirmed by an IRC as assessed by the modified Lugano 
Classification (Cheson, 2014) for Cohorts A and B (PTCL) based on CT and after at least 8 weeks 
from the first assessment by Olsen Criteria (Olsen, 2011) for Cohort C (TMF). 
 
ORR-2 confirmed by Investigator 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 by 
Olsen Criteria (Olsen, 2011) for Cohort C (TMF). 
 
DOR 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 by Olsen Criteria (Olsen, 2011) for Cohort C 
(TMF) based on IRC assessment. 
 
Assessment of non-compartmental PK parameters including Cmax, AUC, volume of distribution at 
steady state (Vss), half-life (t1/2). 
 
Incidence of subjects who develop anti-drug antibodies (ADA) during treatment in blood and their 
neutralizing potential.  
 
QOL as measured by European Quality of Life 5-Dimensional (EQ-5D) for Cohorts A and B, and by 
Skindex-29 for Cohort C. 
4.3 
Exploratory endpoints 
 
 
 


 
 
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4.4 
Safety endpoints 
The safety endpoints of this study are: 
 
Number and frequency of treatment-related adverse events (AEs). 
 
 
 


 
 
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5 
SAMPLE SIZE AND POWER 
Refer to protocol section 8.8.1. 
 


 
 
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6 
ANALYSIS POPULATIONS 
6.1 
Full analysis set (FAS) 
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. 
6.2 
COVID analysis set 
The COVID analysis set will include all subjects from the FAS excluding subjects who ended the treatment 
due to COVID-19 before the first post-baseline efficacy assessment. 
 
 
 
 
6.3 
Safety set (Safety) 
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. 
6.4 
Per protocol set (PP) 
The PP set will consist of all subjects in FAS who did not have any major protocol deviations. To support the 
results of the primary analysis on the FAS, the primary analysis will be repeated using PP Set. 
6.5 
Pharmacokinetic set (PK) 
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. 
6.6 
Protocol deviations and exclusions from analysis sets 
Key (defined as deviation that may impact the safety or integrity of the study) and non-key protocol deviations 
to be collected during the study are listed and described in the Protocol Deviation Criteria Determination 
document. This document indicates also among all the deviations which ones may be major (a major deviation 


 
 
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excludes a subject from the PP population). There is no relationship between key/non-key and major/minor 
deviations as a key deviation can be considered as minor for the statistical analyses. 
All deviations will be reviewed at the Classification Meeting through clinical review input provided by 
Sponsor and will be classified as major or minor. Then, exclusions of subjects from analysis sets will be 
identified. The following sources of information will be used to support the inclusion or exclusion of subjects 
in analysis sets: 
 
Supportive subject listings, provided by the ICON lead statistician ahead of the Classification Meeting, 
based on data recorded on the eCRF.  
 
Protocol Deviation Logs, provided by ICON Medical. 
 
 


 
 
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8 
STATISTICAL METHODS 
8.1 
General statistical conventions 
All statistical procedures will be completed using SAS version 9.4 or higher. 
Unless otherwise stated, all statistical testing will be two-sided and will be performed using a significance 
(alpha) level of 0.05. Two sided 95% confidence intervals (CI) will be provided when relevant. 
Continuous variables will be summarized using descriptive statistics, including number of subjects (n), mean, 
median, standard deviation (SD), minimum (Min) and maximum (Max).  
For categorical variables, summaries will include counts of subjects and percentages. Percentages will be 
rounded to one decimal place. 
For summary purposes, baseline will be defined as the last available pre-dose value. 
 
 
 
 
  
 
 
 
 
 
All subject data, including those derived, will be presented in individual subject data listings. Unless otherwise 
stated, unscheduled visit results will be included in date/time chronological order, within subject listings only. 
All listings will be sorted by cohort, subject number, assessment date/time and visit. Patient’s sex and age 
will be also stated on each listing. Unless otherwise stated, data listings will be based on FAS. 
Subjects who were screened and have signed the informed consent form (ICF) but did not receive any 
treatment will be listed including reason for screen failure or not being treated and any SAE (this will be 
recorded in the medical history). These subjects will not be part of any summary table except for summarizing 
disposition.  
 
 


 
 
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8.2 
Subject disposition 
Subject disposition information will be summarized by cohort and overall. The following number and percent 
of subjects will be summarized: 
- 
Subjects who are pre-screened.  
- 
Subjects who are screened. 
- 
Subjects who are screen failures. 
- 
Subjects enrolled for the treatment period but not treated. 
- 
Subjects included in the FAS. 
- 
Subjects included in the FAS and have at least one post-baseline efficacy assessment. 
- 
Subjects included in the COVID analysis set. 
- 
Subjects included in the safety set. 
- 
Subjects included in the per protocol set. 
- 
Subjects included in the PK set. 
- 
Subjects who discontinued the treatment phase. 
o Subjects impacted by COVID-19 who discontinued the treatment phase. 
o Subjects affected by COVID-19 who discontinued the treatment phase. 
- 
Subjects who performed the final study visit. 
- 
Subjects who remained in response at the end of the treatment. 
- 
Subjects who did not remain in response at the end of the treatment. 
- 
Subjects who completed the study. 
- 
Subjects who discontinued the study. 
The number of subjects in FAS will be used as the denominator for the percentage calculation. Subject 
disposition and subject classification in each analysis population will be listed. 
8.3 
Protocol deviations 
Major deviations (as defined in section 6.6) will be summarized by cohort. 
Protocol deviations identified on protocol deviation Logs from ICON Medical will be listed, including the 
classification of major and minor deviations. The inclusion/exclusion criteria violated at Pre-screening and at 
Screening visits will be also listed. 
8.4 
Demographics and baseline characteristics 
8.4.1 Demographics 
The following demographic parameters will be summarized descriptively or by using frequencies on FAS: 


 
 
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- 
Age. 
- 
Sex. 
- 
Race. 
- 
Ethnicity. 
- 
Female of childbearing potential. 
- 
Height at baseline. 
- 
Weight at baseline. 
- 
Body mass index (BMI) at baseline. 
- 
Eastern Cooperative Oncology Group (ECOG) performance status at baseline. 
- 
Electrocardiogram (ECG) interpretation at baseline. 
- 
Systolic blood pressure (mmHg) at baseline. 
- 
Diastolic blood pressure (mmHg) at baseline. 
- 
Heart rate (beats/min) at baseline. 
- 
Respiratory rate (breaths/min) at baseline. 
- 
Temperature (°C) at baseline. 
8.4.2 Baseline and disease characteristics 
The following baseline and disease characteristics parameters will be summarized descriptively or by using 
frequencies on FAS: 
- 
Time since initial diagnosis (months). 
- 
Cancer type. 
- 
Cancer sub-type (only for PTCL subjects). 
- 
CD30 expression level (only for PTCL subjects) (using categories: ≥1% to <5%, ≥5% to <10%, ≥10% 
to <50%, ≥50%). 
- 
Ann Arbor stage and Ann Arbor stage extension at initial diagnosis (only for PTCL subjects). 
- 
Ann Arbor stage and Ann Arbor stage extension at Screening (only for PTCL subjects). 
- 
TNMB staging at baseline (only for TMF subjects). 
- 
Laboratory parameters: 
o Alanine transaminase (ALT). 
o Aspartate transaminase (AST). 
o Lactate dehydrogenase (LDH). 
o Albumin. 
o Total bilirubin. 
o Creatinine. 


 
 
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o C-reactive protein (CRP). 
o Platelet count. 
o Hemoglobin. 
o White blood cells (WBC). 
o Absolute neutrophils. 
o Absolute monocytes. 
o Absolute lymphocytes. 
o Absolute eosinophils. 
o Absolute basophils. 
- 
Modified Severity Weighted Assessment Tool (mSWAT) total score. 
- 
Composite Assessment of Index Lesion Severity (CAILS) total score. 
- 
Prior systemic therapies (yes/no). 
- 
Prior cancer surgeries (yes/no). 
- 
Prior radiation therapies (yes/no). 
These parameters and some other baseline and disease characteristics parameters will be listed for the FAS. 
8.4.3 Medical history 
A summary of medical history will be presented by system organ class (SOC) and preferred term (PT) coded 
using Medical Dictionary for Regulatory Activities (MedDRA) version 22.0 or higher on the FAS. 
Medical history findings will be also listed. 
8.4.4 Prior and concomitant medications 
Medications used in this study will be coded by using the latest available version of the World Health 
Organization Drug Dictionary Enhanced (WHODDE) (March 2019 or later).  
Prior medications are defined as those medications with a start date prior to the first dose of study drug. 
Concomitant medications are defined as those medications with a start date on or after the first dose of study 
drug. 
Prior and concomitant medications will be summarized separately using frequency tables by ATC class (ATC 
Level 2) and preferred name by cohort on FAS. 
A listing will be also provided for subjects’ prior and concomitant medications. 
 


 
 
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8.4.5 Prior anti-cancer medications 
Prior systemic therapies, prior cancer surgeries and prior radiation therapies will be summarized by cohort on 
FAS.  
For prior systemic therapies, the following data will be summarized: 
- 
Subjects with at least one prior systemic therapy. 
- 
Number of treatment lines. 
- 
Time between end of last treatment to study start (months). 
- 
Medication type. 
- 
Best overall response. 
- 
Best response to Brentuximab vedotin (preferred term =’BRENTUXIMAB VEDOTIN’). 
- 
Reason for discontinuing systemic therapy.  
- 
Systemic therapies classified by WHODDE ATC class (ATC Level 2) and preferred name. 
Transplants and non-transplant therapies will be summarized separately. 
Prior cancer surgeries will be summarized by MedDRA SOC and PT. 
For prior radiation therapies, the following data will be summarized: 
- 
Subjects with at least one prior radiation therapy. 
- 
Number of prior radiation therapies. 
- 
Time between end of last radiation therapy to study start (months). 
- 
Type of radiation therapy. 
- 
Intent. 
- 
Settings. 
- 
Best overall response to radiation therapy. 
8.5 
Exposure to study treatment 
8.5.1 AFM13 study drug 
The following parameters, relative to AFM13 drug administration, will be calculated and summarized by 
cohort using descriptive statistics for the FAS: 
- 
Number of infusions of AFM13. 
- 
Dose exposure (weeks). 
- 
Cumulative dose (mg). 
- 
Dose intensity (mg/week). 
- 
Relative dose intensity (%). 


 
 
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The number of infusions with interruptions and dose modifications (including the reasons) will be also 
summarized by cohort. The number of subjects who take the 200 mg dose during the entire study will be also 
summarized (see Section 8.8.5). 
Listing will be provided for AFM13 administration and exposure.  
8.5.2 Premedications 
The following medications taken before each AFM13 study drug administration will be listed and 
summarized: 
- 
H1 antihistamine/H2 antagonist/Antihistamine. 
- 
Analgesic/Fever reducer.. 
- 
Nonsteroidal anti-inflammatory drugs (NSAIDs). 
- 
Glucocorticoid/Corticosteroid. 
- 
Other.  
NSAIDs and “other” medications are selected based on a list of ATCs and/or preferred names that Sponsor 
will provide. For - H1 
antihistamine/H2 
antagonist/Antihistamine, 
Analgesic/Fever 
reducer 
and 
Glucocorticoid/Corticosteroid categories, Sponsor will also provide the list of ATCs and/or preferred names 
but this will be also based on the study drug administration CRF page questions relative to antihistamine, 
acetaminophen and dexamethasone (or equivalent steroid) intakes. 
These premedications will be summarized by visit.  The medications collected during the study (in the prior 
and concomitant medications CRF pages) are not collected related to a specific visit. Consequently, the 
following rule will be used to associate the premedications to a visit: 
If premedication start date = Cycle X Day Y drug administration, the medication will be associated to the 
visit Cycle X Day Y. To be considered as a premedication, the indication of use should be “Other” or 
“Condition under study” or “Prophylaxis”. 
For premedications which are recorded only once during the study in the CRF (recorded with frequency 
= Once weekly), if the medication intake dates include the study drug administration date, the medication 
the medication will be associated to the study drug administration visit. 
 
To evaluate the relationship between dose intakes and pre-medications, an overall shift table will be generated 
between the following data to summarize the number of infusions received in each category (ie, number of 
infusions where the dose administered was > 0 mg): 
- 
Infusion interrupted (Yes/No) 


 
 
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- 
H1 antihistamine/H2 antagonist/Antihistamine intake (Yes/No) 
- 
Analgesic/Fever reducer intake (Yes/No) 
- 
Glucocorticoid/Corticosteroid intake (Yes/No). 
8.6 
Efficacy analyses 
This section addresses the analyses to be conducted on the primary, secondary and exploratory efficacy 
variables. 
The FAS will be the primary population for all efficacy related endpoints and the primary objective. 
Sensitivity analyses on all subjects who received at least one dose of AFM13 and had at least one post-baseline 
efficacy assessment and on PP set will be conducted to support the results of the primary analysis, when 
deemed necessary (ie, if the number of subjects in these populations is different compared to the FAS). 
 
 
Each efficacy endpoint will be derived separately for IRC and Investigator. Consequently, endpoints using 
IRC assessments, will be derived using only responses provided by IRC regardless of Investigator responses. 
Similarly, endpoints using Investigator assessments will be derived using only responses provided by 
Investigator regardless of IRC responses.  
8.6.1 Analysis methods 
8.6.1.1 Multiplicity 
Not applicable. 
8.6.1.2 Treatment by center interaction analysis (multi-center study) 
Not applicable. 
8.6.1.3 Overall response date of assessment 
If the date of assessment of overall response is not recorded/collected in the CRF then this will be assigned to 
the maximum of all assessments dates which belongs to the disease assessment visit. 
8.6.1.4 Derivation of post-baseline disease assessments visits 
In the CRF, the post-baseline disease assessments are not linked to study visits. Consequently, this will be 
performed by programming as per APPENDIX A. 
8.6.2 Analysis of efficacy endpoints 
The primary endpoint is based on the IRC PET-CT-based metabolic responses. Secondary endpoints are based 


 
 
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on IRC CT based radiologic responses and on Investigator (CT or FDG-PET (=PET-CT)) responses. 
Overall response 
Within each visit an overall response will be determined by the IRC and Investigator on CT-based 
radiographic responses and FDG-PET (=PET-CT) based metabolic responses separately 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 who cannot be evaluated for response will be categorized as not evaluable (NE).  
Best overall response (BOR) 
The best overall response is the best response recorded from the start of the treatment until disease 
progression/recurrence or death. All disease responses obtained after progressive disease, start of new anti-
cancer therapy or a transplant are excluded from the best overall response. Best is defined as the first response 
when all a subject’s response assessments are sorted by complete response/complete radiologic 
response/complete metabolic response (CR), partial response/partial remission/partial metabolic response 
(PR), stable disease/no metabolic response (SD), pseudoprogression, progressive disease/progressive 
metabolic disease (PD), not evaluable (NE).  
The subject's best response assignment will depend on the achievement of the measurement criteria 
(confirmation is not required). BOR will be summarized using a frequency table by cohort. For Cohorts A 
and B, BOR is derived for radiographic (using only CT-based responses) and metabolic responses (using only 
FDG-PET (=PET-CT) based responses) separately.  
Overall response rate (ORR) 
ORR is calculated as the proportion of subjects with a CR or PR. Subjects without at least one post-baseline 
response assessment will be treated as non-responders. 
ORR and Pearson-Clopper 95% confidence interval (CI) will be displayed separately for CT-based response 
and FDG-PET (=PET-CT) based response. CR and PR rates and their Pearson-Clopper 95% CI will be also 
displayed separately. 
As the study design is based on a Simon’s two stage design (See Section 5), an exact binomial test will be 
performed to analysed the ORR of the Cohorts A and C at the final analysis only. The one-sided p-value will 
be displayed. The tested hypotheses are as follows for each cohort: 
Cohort A: H0: p≤0.25  
                 H1: p>0.25 


 
 
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Cohort C: H0: p≤0.05 
                 H1: p>0.05 
For all response assessments, swimmer plots will be presented. All response assessments will be also listed. 
The above analyses (overall response, BOR and ORR) will be performed for each cohort and for: 
Response 
evaluator 
Population of analysis 
Analysis order 
IRC 
FAS 
Primary analysis 
IRC 
FAS with at least one post-
baseline efficacy 
assessment 
Sensitivity analysis, if deemed necessary (based on the 
number of subjects included in that population after the 
Classification Meeting) 
IRC 
COVID analysis set 
Sensitivity analysis, if deemed necessary (based on the 
number of subjects included in that population after the 
Classification Meeting) 
IRC 
PP set 
Sensitivity analysis, if deemed necessary (based on the 
number of subjects included in that population after the 
Classification Meeting) 
Investigator 
FAS 
Secondary analysis 
 
 
 
 
 
Theses analyses will be also repeated for the subgroups defined in Section 8.8.5 for the FAS. 
  
Duration of response (DOR)  
The DOR is defined as time from first assessment of PR or CR to the first assessment of progressive disease 
or death due to any cause separately for IRC and Investigator using respectively only IRC or Investigator 
assessments. DOR will be censored for IRC assessments using Table 1 and Investigator assessments using 
Table 3 when analyses are performed on FAS or PP set. The Table 2 and Table 4 will be used when the 
analyses are performed on the COVID analysis set: 
 
 


 
 
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Table 1: Independent Review Committee Assessments (IRC) Censoring Rules  
Event 
Event or censored date 
Event or 
censored 
Progression (as determined by IRC) 
Date of progression (as determined by IRC) 
Event 
Death due to any cause 
Date of death 
Event 
PD (as determined by IRC) or death after 1 missed 
assessment 
(ie, >= 59 days between 2 assessments until Cycle 4 
and >= 87 days from Cycle 5) 
Date of PD (as determined by IRC) or death 
Event 
PD (as determined by IRC) or death after 2 or more 
missed assessments   
(ie, >= 118 days between 2 assessments until Cycle 
4 and >= 174 days from Cycle 5) 
Date of last disease assessment before 
missed assessments 
Censored 
No baseline tumour assessment 
Date of first study drug 
Censored 
No post-baseline response assessment 
Date of first study drug 
Censored 
Start of new anti-cancer therapy before progression 
(as determined by IRC) or death 
Date of last disease assessment prior to new 
anti-cancer therapy * 
Censored 
Transplant before progression (progression as 
determined by IRC) or death or start of new anti-
cancer therapy 
Date of last disease assessment prior to date 
of transplant 
Censored 
No progression determined by IRC or death 
Date of last disease assessment 
Censored 
Note: Only disease assessments provided to IRC are included in the analysis. 
* The new anti-cancer therapy information is only collected on the “Survival follow-up’ page but no date is 
collected. Consequently, it is assumed that the new therapy starts between the follow-up where the question 
“Did the patient start any new anti-cancer therapies?” is “Yes” and the previous follow-up. The subject will 
be censored at the last disease assessment prior or on this previous visit. 
 




 
 
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* The new anti-cancer therapy information is only collected on the “Survival follow-up’ page but no date is 
collected. Consequently, it is assumed that the new therapy starts between the follow-up where the question 
“Did the patient start any new anti-cancer therapies?” is “Yes” and the previous follow-up. The subject will 
be censored at the last disease assessment prior or on this previous visit. 
Table 3: Investigator Assessments Censoring Rules 
Event 
Event or censored date 
Event or 
censored 
Progression (as determined by Investigator) 
Date of progression (as determined 
by Investigator) 
Event 
Death due to any cause 
Date of death 
Event 
PD (as determined by Investigator) or death after 1 missed 
assessment  
(ie, >= 59 days between 2 assessments until Cycle 4, >= 
87 days from Cycle 5 and >= 122 days from Survival 
Follow-up) 
Date of PD (as determined by 
Investigator) or death 
Event 
PD (as determined by Investigator) or death after 2 or 
more missed assessments   
(ie, >= 118 days between 2 assessments until Cycle 4, >= 
174 days from Cycle 5 and >= 244 days from Survival 
Follow-up) 
Date of last disease assessment or 
date of last survival contact (for 
Survival Follow-up) before missed 
assessments 
Censored 
No baseline tumour assessment 
Date of first study drug 
Censored 
No post-baseline response assessment 
Date of first study drug 
Censored 
Start of new anti-cancer therapy before progression (as 
determined by Investigator) or death 
Date of last disease assessment or 
date of last survival contact (for 
Survival Follow-up) prior to new 
anti-cancer therapy * 
Censored 


 
 
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Event 
Event or censored date 
Event or 
censored 
Transplant before progression (progression as determined 
by Investigator) or death or start of new anti-cancer 
therapy 
Date of last disease assessment or 
date of last survival contact (for 
Survival Follow-up) prior to date of 
transplant 
Censored 
No progression determined by Investigator or death 
Date of last disease assessment or 
date of last survival contact (for 
Survival Follow-up) 
Censored 
Note: Only disease assessments recorded in the CRF are included in the analysis. 
* The new anti-cancer therapy information is only collected on the “Survival follow-up’ page but no date is 
collected. Consequently, it is assumed that the new therapy starts between the follow-up where the question 
“Did the patient start any new anti-cancer therapies?” is “Yes” and the previous follow-up. The subject will 
be censored at the last disease assessment prior or on this previous visit. 
 
 


 
 
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Note: Only disease assessments collected in the CRF are included in the analysis. 
* The new anti-cancer therapy information is only collected on the “Survival follow-up’ page but no date is 
collected. Consequently, it is assumed that the new therapy starts between the follow-up where the question 
“Did the patient start any new anti-cancer therapies?” is “Yes” and the previous follow-up. The subject will 
be censored at the last disease assessment prior or on this previous visit. 
DOR will be summarized and listed by cohort and for CT and FDG-PET (=PET-CT) based responses 
separately. Duration of CR and duration of PR will be also reported separately.  
DOR will be analyzed using Kaplan-Meier median, its 95% CI (and 25th and 75th percentile) and the estimates 
at 3, 6, 9, 12, etc months. 
Theses analyses will be also repeated for the subgroups defined in Section 8.8.5 for the FAS. 
8.6.3 Analysis of exploratory endpoints 
 
 
 
 
 
  
 
 
 
 
 
 


 
 
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8.7 
Safety analyses 
Safety analyses will be conducted on the safety set and will be performed for all safety variables specified 
below.  
All the data will be summarized by cohort, and cohorts A and B combined. 
No statistical test will be performed. 
8.7.1 Adverse events 
All Adverse events (AEs) will be classified by SOC and PT according to the MedDRA Version 22.0 or higher. 
AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse 
Events (NCI CTCAE) version 5.0. 
In summaries by SOC and/or PT, adverse events will be sorted by decreasing frequency within each SOC 
and/or PT according to the highest subject number in Cohort A.  
AEs will be classified as pre-treatment AEs or treatment-emergent adverse events (TEAEs) defined as 
follows:  
Pre-treatment AE: any AE that started after study enrollment (ICF signed) and before the first dose date of 
study medication. 
TEAE: any AE that was newly developed at or after the first dose date of study drug.  
Related AE: AE will be defined as related if causality is either ‘definitely related’, ‘probably related’, 
‘possibly related’ or missing. 
Details for imputing missing or partial start dates of adverse events are described in section 7.2.2. 
AE summary tables listed below will be presented: 
 
All TEAEs. 
 
All related TEAEs. 
 
TEAEs by maximum severity. 


 
 
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 
Serious TEAEs. 
 
Non-serious TEAEs. 
 
Related serious TEAEs. 
 
Related TEAEs by maximum severity. 
 
TEAEs with NCI CTCAE grades ≥3. 
 
Related TEAEs of NCI CTCAE grades ≥3. 
 
Important medical events (IMEs) (IMEs include only TEAEs): 
o Infusion-related reactions (IRRs). 
o Hepatic TEAEs (selecting events within “Drug related hepatic disorders - comprehensive 
search” Standardized MedDRA Queries (SMQ)). 
o Other IMEs (ie, SAEs with “Other important medical event” reason). 
 
Frequency of IRRs by maximum severity and visit. 
 
TEAEs leading to interruptions or modifications of study drug (action taken as “Drug reduced”, 
“Drug interrupted”, Drug delayed”, “Treatment held”). 
 
TEAEs leading to premature discontinuation of study drug (action taken as “Drug discontinued”). 
 
AEs leading to death. 
 
Related AEs leading to death. 
 
Frequent non-serious TEAEs (SOCs or PTs with at least 5% of subjects within the cohort). 
 
Glucocorticoid/Corticosteroid premedications (Yes/No) and frequency of IRR by maximum severity 
and visit. 
 
All AEs will be summarized by MedDRA SOC, PT and cohort using frequency counts and percentages (ie, 
number and percentage of subjects with an event). In addition, an overall summary for the categories above 
will be prepared by cohort. 
Where a subject has the same adverse event, based on SOC and/or PT, reported multiple times, the subject 
will only be counted once at the SOC and/or PT level in adverse event frequency tables. 
When reporting adverse events by severity, in addition to providing a summary table based on the event 
selection criteria detailed above, summary table will also be provided based on the most intense event 
regardless of the relationship to study treatment. 
 


 
 
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IRR will be summarized by visit and cohort. But IRRs are collected during the study without being linked to 
a specific visit. Consequently, the following rule will be used to assign the IRRs to a visit: 
If study drug administration at Cycle X Day Y ≤ IRR start date/time ≤ study drug administration at 
Cycle X Day Y + 24 hours then the visit is assigned to Cycle X Day Y; else visit is assigned to 
Unscheduled (Unscheduled visit should be also included in the “by visit” table). 
8.7.2 Clinical laboratory evaluations 
For the purposes of summarization in both the tables and listings, all laboratory values will be presented in 
standard units.  
Laboratory results will be graded by NCI CTCAE version 5.0. For the tests without grading, only the 
classification according to normal ranges will be done. 
Hematology (including coagulation), chemistry and urinalysis will be summarized by cohort, visit and 
parameters in each category.  
If a lab value is reported using a nonnumeric qualifier eg, less than (<) a certain value, or greater than (>) a 
certain value, the given numeric value will be used in the summary statistics, ignoring the nonnumeric 
qualifier. This will be explained in the footnotes of the respective outputs. 
Descriptive statistics for actual measurement and change from baseline at scheduled visits will be performed.  
Urinalysis parameters will be also summarized by frequency counts by cohort and for each scheduled visit 
for nonnumeric parameters. 
Shift tables for CTCAE grades and normal ranges from baseline to each visit and to worst post-baseline visit 
will be presented.  
All laboratory tests will be listed. A separate listing for abnormal lab values (≥Grade 3, and low/high values) 
will be presented. 
 
Liver and renal events 
The subjects with liver events at any post-baseline visit will be summarized and listed for the following 
categories:  
 
ALT or AST > 3 × upper limit of normal (ULN). 
 
Alkaline phosphatase (ALP) > 2 × ULN. 
 
Total bilirubin > 2 × ULN. 
 
(ALT or AST > 3 × ULN) and total bilirubin > 2 × ULN and ALP > 2 × ULN. 


 
 
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 
LDH > 2 x ULN. 
 
Albumin < lower limit of normal (LLN). 
 
Glomerular filtration rate (GFR) in mL/min/1.73 m² will be summarized and listed at each visit and to worst 
post-baseline visit with the following categories: <15, [15-30[, [30-45[, [45-60[, [60-90[ and ≥ 90. 
GFR values will be derived using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation: 
𝐺𝐹𝑅= 141 ×  𝑀𝐼𝑁 (𝐶𝑟𝑒𝑎𝑡
𝐾
, 1)
𝛼
× 𝑀𝐴𝑋(𝐶𝑟𝑒𝑎𝑡
𝐾
, 1)
−1.209
× 0.993𝐴𝑔𝑒× 
1.018 [𝑖𝑓 𝐹𝑒𝑚𝑎𝑙𝑒] × 1.159 [𝑖𝑓 𝐵𝑙𝑎𝑐𝑘 𝑜𝑟 𝐴𝑓𝑟𝑖𝑐𝑎𝑛 𝐴𝑚𝑒𝑟𝑖𝑐𝑎𝑛] 
where 
Creat is serum creatinine in µmol/L 
K is 61.9 for females and 79.6 for males 
α is -0.329 for females and -0.411 for males. 
 
 
 
 
 
 
 
 
 
8.7.4 Vital signs 
Descriptive statistics for actual measurements of vital signs (systolic/diastolic blood pressure (mmHg), 
respiratory rate (breaths/min), heart rate (beat/min), temperature (◦C)), weight (kg) and BMI (kg/m²), and 
changes from baseline for each time point will be presented by cohort.   
Listing of vital signs data will be presented. 
8.7.5 Physical examinations 
A listing will be provided for physical examination by cohort, subject, visit, body system, and description of 
abnormalities. 


 
 
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8.7.6 Electrocardiograms 
Shift tables from baseline (Normal/Abnormal-clinically significant/Abnormal–not clinically significant) to 
each time point and to worst post-baseline ECG interpretation will be summarized for ECG interpretation 
data. Descriptive statistics for actual and changes from baseline will be displayed for heart rate (msec), QRS 
interval (msec), RR interval (msec), PR interval (msec), QT internal (msec), QTc internal (msec). 
ECG data will be listed overall and a separate listing for any clinically significant finding in ECG values will 
be provided. 
8.7.7 ECOG performance status  
Shift table for performance status (0 to 5 grades) of subjects from baseline to the worst post-baseline visit will 
be presented by cohort. 
A listing of the performance status of subjects will be provided by visit. 
8.8 
Other analysis 
8.8.1 Statistical analysis for PK data 
AFM13 serum concentrations will be summarized by cohort, study cycle, and nominal time points. All table 
summaries and figures for PK concentrations will be compiled using the PK set and will be presented by 
cohort. For concentration values below the limit of quantification (BLQ), a concentration value of zero will 
be included for the computation of arithmetic mean and a concentration value of ½ LLOQ will be included 
for the computation of geometric mean. 
Individual subject listings for concentration data will be provided. Plots of serum concentrations (geometric 
mean (+/- coefficient of variation (CV)) will be presented in both original and semi-logarithmic scales. 
PK parameters data will be converted into Study Data Tabulation Model (SDTM) datasets and will be 
summarized in a separate noncompartmental analysis (NCA) report. 


 
 
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8.8.3 Quality of life analyses 
EQ-5D 
EQ-5D will be used to assess the subject’s 5 dimensions - mobility, self-care, usual activities, pain/discomfort 
and anxiety/depression. Shift tables for EQ-5D pain/discomfort score (“no pain or discomfort”, “moderate 
pain or discomfort” and “extreme pain and discomfort”) from baseline to each visit will be presented for 
cohorts A and B by visit using FAS. The health state scale actual and change form baseline values will be 
also summarized. 
Skindex-29 
The Skindex-29 is composed of 29 items investigating the three domains: Emotions, Symptoms and 
Functioning. These domains will be derived for each visit as below: 
Domains and clusters: 
Domains/ 
Scale 
Number 
of items 
Clusters of items 
Direction of domains 
Emotions 
10 
3; 6; 9; 12; 13; 15; 21; 23; 26; 28 
Higher score = higher 
impact of skin disease 
Symptoms 
7 
1; 7; 10; 16; 19; 24; 27 
Functioning 
12 
2; 4; 5; 8; 11; 14; 17; 20; 22; 25; 29; 30 
Scoring procedure of each domain: 
1. All responses are transformed to a linear scale of 100. 
Never  
  
= 0 
Rarely    
= 25 
Sometimes   
= 50 
Often  
  
= 75 
All the time  
= 100 
 
2. A scale score is the mean of non-missing items in a given scale (note: item 18 is a single item, not 
included in scoring): 
a. If responses to more than 25% of items are missing overall the questionnaire is eliminated 
(ie, if > 7 items are missing among the 29 items). 
b. If any scale has more than 25% of the responses missing, the scale is missing (ie, if > 2 items 
for Emotions or > 1 item for Symptoms or > 3 items for Functioning are missing). 


 
 
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c. An item with multiple answers is considered missing. 
Sum score: 
The sum score is derived as the average of the three scale scores for each subject and visit.  
 
The summary statistics of absolute and change from baseline values for the 3 scale scores and the sum score 
will be provided at each visit for cohort C using FAS.  
Supportive by-subject listings will also be provided for EQ-5D-3L and Skindex-29.  
8.8.4 Biomarker analysis 
 
 
 
8.8.5 Subgroup analysis 
The following subgroup analyses will be performed for the final analysis: 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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- 
 
 
8.9 
Interim analysis 
 
 
 
  
 
 
 
The following analyses will be generated for the interim analysis: 
 
Disposition. 
 
Demographic and baseline characteristics. 
 
Disease characteristics. 
 
Exposure to treatment (AFM13 and premedications) 
 
Overall response. 
 
Duration of response. 
 
Adverse events. 
 
 
 
 


 
 
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9 
 
 
 
 
 
 
 
 
 


 
 
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10 
REFERENCES 
1. 
ICH Topic E3: Structure and Content of Clinical Study Reports (CPMP/ICH/137/95- adopted 
December 1995). 
2. 
ICH Topic E9: Statistical Principles for Clinical Trials (CPMP/ICH/363/96 – adopted March 1998). 
3. 
ICH Topic E9(R1): Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity 
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Cheson BD, Bennett JM, Grever M, et al. National Cancer Institute-sponsored Working Group 
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Cheson B, Fisher R, Barrington S, et al. Recommendations for Initial Evaluation, Staging, and 
Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. J. Clin. 
Oncol. 2014;32(27):3059-3068. 
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Olsen E, Whittaker S, Kim Y, et al. Clinical end points and response criteria in mycosis fungoides 
and Sézary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, 
the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of 
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2607 
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Simon, R. Optimal Two-Stage Designs for Phase II Clinical Trials. Controlled Clin. 
Trials.1989;10(1):1-10. 
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Skindex Scaling and scoring, Version 2.0, February 2012, MAPI Research Trust. 
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Protocol Deviation Criteria Determination document: Document type “Protocol Deviation Criteria 
Template” (document type ID: 103.11) of the eTMF. 


 
 
Final Analysis 
Statistical Analysis Plan (SAP) 
 
 
 
 
 
Statistical Analysis Plan 
Protocol Number: AFM13-202 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019                   
               Version: FINAL 3.0, Date: 13 Sep 2022
Page 46 of 48
(Ref. BST004-SOP) 
 
11 
APPENDIX A 
For each disease assessment visit, the visit name will be derived as follows: 
 
Step 1: Determine the minimum and maximum dates per visit as follows: 
 
For Lugano (within the same disease assessment visit): 
DateINF = MIN ( 
TU.TUDTC (Imaging (modified Lugano)),  
TR.TRDTC (Imaging (modified Lugano)),   
TU.TUDTC (New Lesions (modified Lugano)), 
TR.TRDTC (New Lesions (modified Lugano)), 
TU.TUDTC (Tissue Sites Involved), 
TR.TRDTC (Tissue Sites Involved), 
TU.TUDTC (FDG-PET), 
TR.TRDTC (FDG-PET), 
PR.PRDTC (FDG-PET) ) 
 
DateSUP = MAX ( 
TU.TUDTC (Imaging (modified Lugano)),  
TR.TRDTC (Imaging (modified Lugano)),   
TU.TUDTC (New Lesions (modified Lugano)), 
TR.TRDTC (New Lesions (modified Lugano)), 
TU.TUDTC (Tissue Sites Involved), 
TR.TRDTC (Tissue Sites Involved), 
TU.TUDTC (FDG-PET), 
TR.TRDTC (FDG-PET), 
PR.PRDTC (FDG-PET) ) 
 
 
 
 


 
 
Final Analysis 
Statistical Analysis Plan (SAP) 
 
 
 
 
 
Statistical Analysis Plan 
Protocol Number: AFM13-202 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019                   
               Version: FINAL 3.0, Date: 13 Sep 2022
Page 47 of 48
(Ref. BST004-SOP) 
 
For Olsen (within the same disease assessment visit): 
DateINF = MIN ( 
TU.TUDTC [Imaging (Olsen)],  
TR.TRDTC [Imaging (Olsen)],   
TU.TUDTC (New Lesions (Olsen)), 
TR.TRDTC (New Lesions (Olsen)), 
FA.FADTC (TNMB Staging), 
QS.QSDTC (mSWAT), 
QS.QSDTC (CAILS), 
LB.LBDTC (Flow cytometry for Olsen criteria), 
PR.PRSTDTC (Lesion Photography), 
PR.PRSTDTC (Biospy (Olsen criteria), 
MI.MIDTC (Biospy (Olsen criteria) ) 
 
DateSUP = MAX ( 
TU.TUDTC [Imaging (Olsen)],  
TR.TRDTC [Imaging (Olsen)],   
TU.TUDTC (New Lesions (Olsen)), 
TR.TRDTC (New Lesions (Olsen)), 
FA.FADTC (TNMB Staging), 
QS.QSDTC (mSWAT), 
QS.QSDTC (CAILS), 
LB.LBDTC (Flow cytometry for Olsen criteria), 
PR.PRSTDTC (Lesion Photography), 
PR.PRSTDTC (Biospy (Olsen criteria), 
MI.MIDTC (Biospy (Olsen criteria) ) 
 
 
 


 
 
Final Analysis 
Statistical Analysis Plan (SAP) 
 
 
 
 
 
Statistical Analysis Plan 
Protocol Number: AFM13-202 
BST004-SOP-T02/Version 3.0/Effective: 16 December 2019                   
               Version: FINAL 3.0, Date: 13 Sep 2022
Page 48 of 48
(Ref. BST004-SOP) 
 
Step 2: Assign the visit name as follows: 
 
If (SV.SVSTDTC – 7 <= DateINF <= SV.SVSTDTC + 7)  
or (SV.SVSTDTC – 7 <= DateSUP <= SV.SVSTDTC + 7)  
or (DateINF < SV.SVSTDTC – 7 AND DateSUP > SV.SVSTDTC + 7) then AVISIT = SV.VISIT; 
Else AVISIT = “Unscheduled”. 
 
Notes: 
- 
Visits planned per protocol to have disease assessments are considered from SV. 
- 
If at least one assessment of the disease assessment visit is within the time-window then all the 
assessments are assigned to the visit.