[177Lu]-NeoB in Patients With Advanced Solid Tumors and With [68Ga]-NeoB Lesion Uptake
[177Lu]-NeoB in Patients With Advanced Solid Tumors and With [68Ga]-NeoB Lesion Uptake
First in Human study to characterize the safety, tolerability, pharmacokinetics (PK),
 distribution, radiation dosimetry, and anti-tumor activity of [177Lu]-NeoB in patients with
 advanced solid tumors known to overexpress GRPR and with [68Ga]-NeoB lesion uptake.
Inclusion Criteria:

 -  Signed informed consent prior to participation

 -  Adult patients with advanced solid tumors known to overexpress GRPR

 -  [68Ga]-NeoB tumor lesion uptake on PET/CT or PET/MRI scan at screening visit (>50% of
 lesions detected with conventional imaging are identified as well by [68Ga]-NeoB
 uptake)

 -  At least one measurable lesion per RECIST 1.1/RANO with a [68Ga]-NeoB uptake

 -  Patients for whom no standard therapy is available, tolerated or appropriate

 -  Presence of at least one tumor lesion confirmed with low-dose CT or MRI acquired
 together with the [68Ga]-NeoB PET

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

 -  Life expectancy more than 6 months.

 Exclusion Criteria:

 -  Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 60
 mL/min or serum creatinine > 1.5 x ULN.

 -  Platelet count of < 75 x 10e9/L

 -  Absolute neutrophil count (ANC) < 1.0 x 10e9/L

 -  Hemoglobin < 9 g/dL

 -  alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x upper limit
 of normal (ULN) if no demonstrable liver metastases of > 5 x ULN in the presence of
 liver metastases

 -  Total bilirubin > 1.5 ULN, except for patients with documented Gilbert's syndrome who
 are eligible if total bilirubin ≤ x ULN

 -  Serum amylase and/or lipase > 1.5 ULN

 -  Known or expected hypersensitivity to [177Lu]-NeoB, [68Ga]-NeoB or any of their
 excipients

 -  Impaired cardiac function or clinically significant cardiac disease, including any of
 the following:

 -  Clinically significant and/or uncontrolled heart disease such as congestive heart
 failure requiring treatment (New York Heart Association (NHYA) grade ≥2),
 uncontrolled arterial hypertension or clinically significant arrhythmia

 -  LVEF < 50% as determined by echocardiogram (ECHO)

 -  QTcF > 470 msec for females and QTcF >450 msec for males on screening
 electrocardiogram (ECG) or congenital long QT syndrome

 -  Acute myocardial infarction or unstable angina pectoris < 3 months prior to study
 entry

 -  Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs
 or with fasting plasma glucose > 160 mg/dL (8.9 mmol/L)

 -  Patients with history of or ongoing acute or chronic pancreatitis

 -  Prior administration of a radiopharmaceutical with therapeutic intent within a period
 corresponding to 10 half-lives of the radionuclide used in such radiopharmaceutical

 -  Prior External Beam Radiation Therapy (EBRT) to more than 25% of the bone marrow

 -  Patients with a bone scan showing an excessive skeletal radiopharmaceutical uptake
 with absent or faint activity in soft tissues and the genitourinary tract due to
 diffuse bone/bone marrow metastases in bone scan also called a "superscan"

 -  Prior treatment with Radium=223

 -  Patients who have changed the dose of systemic steroid therapy within less than 2
 weeks prior to study entry or patients for whom steroid dose increase is anticipated
 during the study.

 -  Patients who have received prior systemic anti-cancer treatment within the following
 time frames:

 -  Cyclical chemotherapy within a period that is shorter than the cycle length used
 for that treatment (e.g. 6 weeks for nitrosourea, mitomycin-C) prior to starting
 study treatment

 -  Biologic therapy (e.g. antibodies), continuous or intermittent small molecule
 therapeutics, or any other investigational agents within a period which is ≤ 5
 T1/2 or ≤ 4 weeks (whichever is shorter) prior to starting [177Lu]-NeoB treatment

 -  History of somatic or psychiatric disease/condition that may interfere with the
 objectives and assessments of the study.

 -  Malignant disease, other than that being treated in this study. Exceptions to this
 exclusion include the following: malignancies that were treated curatively and have
 not recurred within 2 years prior to study treatment; completely resected basal cell
 and squamous cell skin cancers; any malignancy considered to be indolent and that has
 never required therapy; and completely resected carcinoma in situ of any type

 -  pregnant or breast-feeding women

 -  women of child-bearing potential, defined as all women physiologically capable of
 becoming pregnant, are not allowed to participate in this study UNLESS they are using
 highly effective methods of contraception throughout the study and for 6 months after
 study drug discontinuation. Highly effective contraception methods include:

 -  Total abstinence

 -  Male or female sterilization

 -  Combination of any two of the following (a+b or a+c or b+c)

 1. Use of oral, injected, or implanted hormonal methods of contraception. In
 case of use of oral contraception, women should be stable on the same pill
 for a minimum of 3 months before taking study treatment.

 2. Placement of an intrauterine device (IUD) or intrauterine system (IUS).

 3. Barrier methods of contraception: condom or occlusive cap (diaphragm or
 cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
 suppository. Post-menopausal women are allowed to participate in this study.
 Women are considered post-menopausal and not of child bearing potential if
 they have had 12 months of natural (spontaneous) amenorrhea with an
 appropriate clinical profile (e.g. age appropriate, history of vasomotor
 symptoms) or six months of spontaneous amenorrhea with serum
 Follicle-Stimulating Hormone (FSH) levels > 40 mIU/mL [for US only: and
 estradiol < 20 pg/mL] or have had surgical bilateral oophorectomy (with or
 without hysterectomy) or tubal ligation at least six weeks prior to
 screening. In the case of oophorectomy alone, only when the reproductive
 status of the woman has been confirmed by follow-up hormone level assessment
 is she considered not of child bearing potential. Sexually active males must
 use a condom during intercourse while taking the drug and for 6 months after
 stopping treatment and should not father a child in this period. A condom is
 required to be used also by vasectomized men in order to prevent delivery of
 the drug via seminal fluid.