This is a phase l multi-centric, single arm, prospective, open, dose-escalation study in
patients with unresectable stage III oder IV melanoma. The trial will include 15 adult
patients. The trial is a classic 3+3 design with 1 Log dose increments and maximum 3 dose
levels of the intravenously administered MB-CART20.1.
Inclusion Criteria:
Male or female patients with
- Histologically confirmed unresectable stage III or stage IV melanoma
- Willingness to provide a tumor biopsy between the screening visit and prior to
administration of the IMP and eight weeks after treatment
- Progressive disease despite treatment with indicated standard therapies. Time window
for decision about progressive disease is to be made depending on the treatment
regimen chosen.
- Measurable lesions according to RECIST1.1
- ECOG (Eastern cooperative oncology group) performance status of 0-2
- Negative serological hepatitis B (HBV) test defined as negative tests for HBsAg and
HBcAb, unless serology is positive due to recent IVIG therapy, HBcAb positivity will
be allowed if HbsAb is present, negative testing of HCVAb, negative human
immunodeficiency virus (HIV) 1/2 test within 6 weeks prior to enrollment.
- Estimated life expectancy of more than 6 months
- At least 18 years of age
- WBC ≥ 2500/µL
- ANC ≥ 1000/µL
- Platelets ≥ 75 x 103/µL
- Hemoglobin ≥ 9 g/dL
- AST ≤ 3 x upper limit of normal (ULN) for patients without liver metastasis
- AST < 5 x ULN for patients with liver metastasis
- Total Bilirubin ≤ 2 x ULN
- patients with Gilbert's Syndrome increase of indirect bilirubin < 6mg/dL
- No childbearing potential (i.e. postmenopausal, absence of menstrual bleeding for at
least 1 year, hysterectomy, bilateral ovariectomy or tubal section/ligation) or
negative pregnancy test at screening and before chemotherapy in women with
childbearing potential. Sexually active female patients of childbearing potential
should use one of the following highly effective methods of contraception (Pearl index
< 1%): hormonal contraceptives (oral, injected, implanted, transdermal), intrauterine
devices or systems (e.g. hormonal and non-hormonal IUD), or vasectomized sexual
partner for at least 1 month before the trial start, during the course of the trial
and in the 6 months following dosing. Sexual abstinence is restricted to true
abstinence ( in line with the preferred and usual lifestyle of the subject).
- male patients, unless surgically sterile, must be using two acceptable methods for
contraception (e.g. spermicide and condom) during the trial and refrain from fathering
a child throughout the trial and for up to 12 months after dosing.
- Signed and dated informed consent before conduct of any trial-specific procedure.
Exclusion Criteria:
- Any evidence of brain metastases
- CNS (central nervous system) disorders and previous strokes, if clinically relevant
- Patients with epilepsy
- Clinically relevant autoimmune disorders or history of clinically relevant autoimmune
disorders
- Patients with T-cell lymphoma
- Treatment with anti-CD20 antibodies or checkpoint blockade inhibitors within 6 weeks
before leukapheresis
- Chemotherapy within 6 weeks prior to leukapheresis
- History of primary immunodeficiency
- Creatinine clearance < 50 ml/min calculated according to the modified formula of
Cockcroft and Gault
- concurrent systemic radiotherapy
- Use of systemic corticosteroids and immunosuppressive medication except prednisone ≤
10 mg QD or equivalent
- Patients with severe cardiac disease (e.g. NYHA Functional Class III or IV, myocardial
infarction within 6 months before inclusion, ventricular tachyarrhythmia requiring
ongoing treatment, unstable angina pectoris)
- Other investigational treatment within 4 weeks before MB-CART20.1 infusion
- Hypersensitivity against any drug or its ingredients/impurities that is scheduled or
likely to be given during trial participation, e.g. as part of the mandatory
lymphodepletion protocol, pre-medication for infusion, rescue medication/salvage
therapies for treatment related toxicities
- Patients in which such medication (likely to be given during trial participation) is
contraindicated for other reasons than hypersensitivity, e.g. live vaccines and
fludarabine.
- Severe pulmonary disease (DLCO and/or FEV1 < 65%, dyspnoea at rest)
- Active systemic fungal, viral or bacterial infection
- Pregnant or lactating women
- Patient's lack of accountability, inability to appreciate the nature, meaning and
consequence of the trial and to formulate his/her own wishes correspondingly
- Patients who have a relationship of dependence or employer employee relationship to
the sponsor or the investigator
- Committal to an institution on judicial or official order