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

Eligibility Criteria

Inclusion Criteria:

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

1. Metastatic castrate resistant prostate cancer (mCRPC);
2. HR+/HER2- breast cancer;
3. Colorectal cancer;
4. Cervical cancer;
5. Cutaneous melanoma;
6. 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. For subjects with prostate cancer, bone lesions may be used to fulfill the eligibility requirements per PCWG3 in lieu of measurable disease per RECIST 1.1.
* Eastern Cooperative Oncology Group (ECOG) status 0-2.
* Sufficient bone marrow capacity and organ function as defined by:

1. White blood cell (WBC) ≥2,500/ mm³
2. Absolute neutrophil count (ANC) ≥1500/mm³
3. Platelets ≥75,000/mm³
4. 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:

1. New York Heart Association (NYHA) class III or IV;
2. QTc > 470 msec for females and QTc >450 msec for males on screening electrocardiogram (ECG) or congenital long QT syndrome;
3. 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.