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

Eligibility 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;
• * 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.