[177Lu]-NeoB in Patients With Advanced Solid Tumors and With [68Ga]-NeoB Lesion Uptake

Inclusion Criteria:

   1. Signed informed consent must be obtained prior to participation in the study.

   2. Adult patients (age >= 18 years old) with any of the following advanced or metastatic
   solid tumors:

   For Phase I: breast cancer, lung cancer, prostate cancer, GIST, GBM For Phase IIa:

   a. Cohort A: Breast cancer with histology as follows: HR positive with ER > 10% of
   nuclei stain, HER-2 negative and HER-2 low based on current practice and medical
   history b. Cohort B: Prostate cancer c. Cohort C: GIST d. Cohort D: Patients affected
   by any advanced/metastatic solid tumor type suspected to overexpress GRPR including
   recurrent GBM, and with moderate impaired renal function defined as creatinine
   clearance (calculated using the Cockcroft-Gault formula, or measured) >= 30 mL/min and
   < 60 mL/min

   3. At least one measurable lesion as per RECIST 1.1, RANO (applicable for GBM only)
   criteria detected on the low-dose CT/MRI (for GBM MRI only) acquired together with the
   [68Ga]-NeoB PET.

   The same identified measurable lesion shows [68Ga]-NeoB uptake on PET/CT or PET/MRI.
   If the only matching lesion is located in the bone, the patient will still be
   eligible.

   4. Patients for whom no standard therapy is available, tolerated or appropriate in both
   Phase I and Phase IIa. Specifically in the Phase IIa breast cancer Cohort A, patients
   need to have completed at least one prior treatment of endocrine therapy (including
   CDk4/6i) and at least one prior chemotherapy (unless contraindicated) in the
   metastatic setting. Patients with prior treatment with trastuzumab deruxtecan,
   alpelisib or elascestrant are also eligible. In case of confirmed presence of
   deleterious or suspected deleterious germline BRCA1 or BRCA2 mutation, the patient
   must also have already received a PARP inhibitor-based therapy.

   5. Patient Eastern Cooperative Oncology Group (ECOG) performance status: For Phase I: =<
   2, For Phase IIa: =<1

Exclusion Criteria:

   1. Patients who have not had resolution, except where otherwise stated in the inclusion/
   exclusion criteria, of all clinically significant toxic effects of prior systemic
   cancer therapy, surgery, or radiotherapy to Grade =<1 (except for alopecia)*.

   2. Creatinine clearance (calculated using Cockcroft-Gault formula, or measured)

   a. For Phase I and Phase IIa (Cohort A, B and C): < 60 mL/min or serum creatinine >
   1.5 x ULN* b. For Phase IIa (Cohort D): < 30 mL/min or >= 60 mL/min

   3. Platelet count of < 75 x 109/L*†

   4. Absolute neutrophil count (ANC) < 1.0 x 109/L*†

   5. Hemoglobin < 9 g/dL*†

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

   7. Total bilirubin > 1.5 x ULN, except for patients with documented Gilbert's syndrome
   who are eligible if total bilirubin =< 3 x ULN*

   8. Serum amylase and/or lipase > 1.5 x ULN*

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

10. 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 (NYHA 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
      [177Lu]- NeoB (IMP1) administration

11. Patients with diabetes mellitus not stable under current treatment as judged by the
   investigator or with hyperglycemia >= CTCAE version 5.0 Grade 2*.

12. Patients with history of or ongoing acute or chronic pancreatitis.

13. Concurrent bladder outflow obstruction or unmanageable urinary incontinence.

14. Administration of a radiopharmaceutical with therapeutic intent within a period
   corresponding to 10 half-lives of the radionuclide used prior to injection of
   [68Ga]-NeoB (IMP2).

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

16. [223Ra]-therapy within the context of diffuse bone or bone-marrow involvement (i.e.,
   "superscan" defined as bone scintigraphy in which there is excessive skeletal
   radioisotope uptake [>20 bone lesions] in relation to soft tissues along with absent
   or faint activity in the genitourinary tract due to diffuse bone/ bone marrow
   metastases).

17. [Removed]

18. 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 [177Lu]-
   NeoB 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 =< 14 days (whichever is shorter) prior to starting [177Lu]-NeoB
      treatment

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

20. 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 [177Lu]-NeoB 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.

21. Pregnant or breast-feeding women

22. 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 7 months after
   study drug discontinuation. Highly effective contraception methods include:

      - True abstinence, when this is in line with the preferred and usual lifestyle of
      the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
      post-ovulation methods), declaration of abstinence for the duration of exposure
      to IMPs, and withdrawal are not acceptable methods of contraception.

      - Male or female sterilization. Vasectomised partner is a highly effective birth
      control method if the partner is the sole sexual partner of the study participant
      and the vasectomised partner has received medical assessment of the surgical
      success.

   Women tubal ligation is an acceptable highly effective contraception method, but
   surgical sterility is defined as bilateral salpingectomy (or bilateral oophorectomy or
   hysterectomy).

   • 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 [177Lu]-NeoB treatment. This is not applicable for
      patients with breast cancer.

      2. Placement of an intrauterine device (IUD) or intrauterine system (IUS). IUS is
      not applicable for patients with breast cancer.

      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 or bilateral
   salpingectomy or 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
   childbearing potential.

   Sexually active males must use a condom during intercourse while taking the drug and
   for 4 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. Female partners of childbearing potential should use
   highly effective contraceptive methods during and up to 4 months after stopping
   treatment.

23. Use of other investigational drugs within 30 days prior to informed consent signature.

      - To be considered as valid to determine the eligibility of a patient, exam results
      of exclusion criteria #2, #3, #4, #5, #6, #7, #8, #10 (except LVEF) and #11 must
      be collected on or after date of patient's informed consent and must be available
      in the source documents for monitoring. LVEF evaluation is permitted within 6
      weeks prior to IMP1 administration, even if performed outside the screening
      period as part of standard routine clinical practice of care, before ICF
      signature.

         - No platelet transfusion, packed red cell transfusion, or G-CSF will be
         allowed during the selection phase after ICF signature.