AFM13 in Relapsed/Refractory Cutaneous Lymphomas

This is an open label, Phase Ib/IIa study designed to evaluate the biologic activity of AFM13
in patients with relapsed or refractory CD30-positive lymphomas with cutaneous involvement.
Primary cutaneous CD30-positive lymphoproliferative disorders (LPD) represent a spectrum from
lymphomatoid papulosis (LyP), to primary cutaneous anaplastic large cell lymphoma (C-ALCL),
to transformed mycosis fungoides (TMF).

The most indolent form of primary cutaneous CD30-positive LPD is LyP, which is usually well
controlled with low dose oral methotrexate, but control of the disease frequently requires
life-long therapy. In contrast, TMF is an aggressive disease which does not have a standard
of care, as patients are treated with various modalities of care with variable outcomes). The
spectrum of other CD30-positive lymphomas with cutaneous presentation is very broad and
involves systemic B and T cell lymphomas with various clinical behaviors.

Redirecting Natural Killer (NK) cells towards these CD30-positive malignancies through direct
engagement with AFM13 is expected to induce tumor cell killing through NK cell-mediated and T
cell-mediated cytotoxicity (i.e., cytotoxic T lymphocytes (CTL)).

The primary objective of this trial is to study the biologic and immunologic effects induced
by the administration of various doses of AFM13, when given as a single agent.

Inclusion Criteria:

- Age ≥18 years

- Histologically confirmed CD30-positive lymphoma with cutaneous involvement

- Failure or intolerance to at least one prior therapy for the current disease

- Presence of one or more cutaneous lesions (measuring at least 1 cm x 1 cm in size; if
only one lesion is present it should be up to the investigator discretion to determine
eligibility)

- Eastern Cooperative Oncology Group (ECOG) performance status ≤2

- Adequate organ and marrow function

- Platelets ≥50,000/μL

- Absolute neutrophil count ≥ 1,000/μL

- Bilirubin < 1.5 x institutional upper limit of normal (ULN) or < 3 x ULN in patients
with Gilbert's disease or liver involvement

- Serum albumin ≥ 2.0 g/dL

- Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤2.5 × institutional
ULN or, in the case of liver involvement by the primary disease AST/ALT ≤ 5 x ULN

- Creatinine≤1.5 x institutional ULN or estimated creatinine clearance of ≥45 mL/min by
the Cockcroft-Gault equation or measured creatinine clearance >45 mL/min

- Females of child bearing potential must have a negative serum pregnancy test with 7
days prior to first dose of treatment. Female patients of childbearing potential and
all male partners must agree to use double barrier methods of contraception throughout
the study period and for at least 30 days following investigational product
discontinuation.

- Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

- Any cancer-related therapy for the current disease within 2 weeks of screening (all
supportive care measures are allowed)

- Major surgery within 2 weeks prior to first dose of study drug

- Evidence of active central nervous system (CNS) involvement

- Requirement for systemic immunosuppressive therapy (e.g. Graft-versus-Host Disease
(GVHD) therapy within 12 weeks before the first dose of study drug)

- Uncontrolled concurrent serious illness.

- Concurrent malignancy or history of a previous malignancy within 3 years prior to
first dose of the current study, unless curatively resected basal, squamous cell
carcinoma of the skin, or cervical carcinoma in situ.

- Active infections including hepatitis B carrier status, hepatitis C virus (HCV)
infection (patients must have a negative Hepatitis B and Hepatitis C viral load at
screening)

- Known HIV-positive status

- Any significant medical conditions, laboratory abnormality, or psychiatric illness
that would exclude the subject from participation or interfere with study treatment,
monitoring and compliance such as:

- unstable angina pectoris, symptomatic congestive heart failure (New York Heart
Association (NYHA) III or IV), myocardial infarction ≤ 6 months prior to first study
drug, clinically significant and uncontrolled cardiac arrhythmia (e.g. atrial
fibrillation/flutter ventricular cardiovascular physiology is allowed),
cerebrovascular accidents ≤ 6 months before study drug start

- severely impaired lung function

- Serious, systemic infection requiring treatment ≤7 days before the first dose of study
drug

- Any severe, uncontrolled disease or condition which in the investigator's opinion, may
put the subject at significant risk, may confound the study results, or impact the
subject's participation in the study.