Safety and Tolerability of ²¹²Pb-DOTAM-GRPR1 ²¹²Pb-DOTAM-GRPR1 in Adult Subjects With Recurrent or Metastatic GRPR-expressing Tumors

Inclusion Criteria:

Male or female ≥18 years old with the following histologically confirmed metastatic or recurrent GRPR-expressing tumors:

Metastatic castrate resistant prostate cancer (mCRPC);
HR+/HER2- breast cancer;
Colorectal cancer;
Cervical cancer;
Cutaneous melanoma;
Non-small-cell lung cancer (NSCLC).

Biopsies must demonstrate the following on immunohistochemistry (IHC):

51-80% positively staining cells; and
Moderate intensity of staining.
Subjects with recurrent disease must have progressed on at least 2 prior systemic therapies.
Presence of at least 1 site of measurable disease per RECIST 1.1 within 1 month prior to Cycle 1 Day 1.
Eastern Cooperative Oncology Group (ECOG) status 0-2.
Life expectancy of at least 12 weeks in the opinion of the investigator at the time of screening.

Sufficient bone marrow capacity and organ function as defined by:

White blood cell (WBC) ≥2,500/ mm³
Absolute neutrophil count (ANC) ≥1500/mm³
Platelets ≥75,000/mm³
Hemoglobin (HgB) ≥9.0 g/dL;

Exclusion Criteria:

Previous whole-body radiotherapy or peptide receptor radionuclide therapy (PRRT) with either alpha or beta emitters, or subjects with mCRPC who have received radium-223 (²²³Ra).
Known hypersensitivity to any component of ²¹²Pb-DOTAM-GRPR1.
Exposure to any other GRPR-targeting therapeutic agents.
History of chronic pancreatitis
History of pneumonitis.

Impaired cardiac function defined as:

New York Heart Association (NYHA) class III or IV;
QTc > 470 msec for females and QTc >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 enrollment.
Cyclical chemotherapy, radiotherapy, or biologic therapy (e.g. antibodies), continuous or intermittent, small molecule therapeutics, or any investigational agents within a period which is ≤ 5 half-lives or ≤ 4 weeks (whichever is longer) prior to Day 1.