Study to Evaluate the Safety and Clinical Activity of UCART123 in Patients With BPDCN

This is a Phase I, first-in-human, open-label, dose-finding study of UCART123 administered
intravenously to patients with BPDCN. he study will consist of two phases, a dose-escalation
phase in relapsed or refractory BPDCN patients and a dose-expansion phase in
relapsed/refractory and newly diagnosed BPDCN patients and relapsed/refractory BPDCN
patients. The safest dose of UCART123 used at the dose level where activity is observed will
be used in the dose-expansion phase. The study's primary assessment is the the safety and
tolerability of UCART123 administered to patients with BPDCN, and to determine the
Recommended Phase 2 Dose (RP2D) of UCART123. T

Main Inclusion Criteria:

- Patients with a diagnosis BPDCN according to World Health Organization (WHO)
classification confirmed by hematopathology;

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;

- Women of childbearing potential must have a negative serum pregnancy test performed
within 7 days prior to enrollment. Within the frame of this study, female patients of
childbearing potential and male patients with partners of childbearing potential must
use an effective method of birth control, as described below, as well as their
partners.

Patients enrolled in the Dose Finding Portion of the Study:

- Patients ≥18 years and ≤80 years old (The 3 first patients at Dose Level 1 will be <
65 years old. Enrollment of patients ≥ 65 years old must be approved by the DSMB after
the completion of cohort 1).

- Patients with histological and/or cytological evidence of BPDCN in the peripheral
blood, bone marrow, spleen, lymph nodes, skin, and/or other sites that is
persistent/recurrent following prior treatment for BPDCN.

Patients enrolled in the Expansion Phase of the Study:

- Age ≥18 years

- Patients with histological and/or cytological evidence of BPDCN in the peripheral
blood, bone marrow, spleen, lymph nodes, skin, and/or other sites that is either
previously untreated or is persistent/recurrent following prior treatment for BPDCN.

Eligibility criteria for UCART123 administration

- No uncontrolled infections;

- Afebrile (<38°C per CTCAE v4.03);

- Normal organ function since eligibility screening, and no new clinical or laboratory
findings that, in the opinion of the investigator, might jeopardize the patient's
safety

- Off all but replacement dose of corticosteroids from Day -7 to Day 28 (replacement
dose is the patient's individualized dose defined for physiological replacement).

Main Exclusion Criteria:

- Previous treatment with investigational gene or chimeric antigen receptor therapy;

- Active or previous central nervous system leukemia involvement

- Presence of active and clinically relevant central nervous system (CNS) disorder;

- Immunosuppression following a Hematopoietic Stem Cell Transplantation (HSCT) within 6
weeks prior to study entry;

- Use of rituximab and other anti-cluster of differentiation antigen 20 (CD20)
antibodies known to have the same epitope as rituximab or anti-cluster of
differentiation antigen 20 (CD20) for which the epitope is unknown within 3 months
prior to enrollment;

- Patients may not receive ≥ 20 mg of prednisone or equivalent between days -7 and +28
of UCART123 infusion. Hydrocortisone required for mineralocorticoid replacement
therapy is authorized at all times as needed clinically. Topical, inhaled, or nasal
route of steroids are permitted;

- Any known uncontrolled cardiovascular disease, pulmonary embolism, hypertension not
adequately controlled by standard medications within 3 months prior to enrollment.

- Active bacterial, fungal or viral infection not controlled by adequate treatment, at
enrollment.