177Lu-PSMA (177Lu-PNT2002) in PSMA-Positive Adenoid Cystic Carcinoma

Inclusion Criteria:

* Histologic confirmation of ACC (primary or metastatic tumor). Central review not required but local pathology review required (at Johns Hopkins or Stanford).
* Patients must have recurrent or metastatic ACC with measurable disease per RECIST 1.1, not amenable to definitive surgery or radiotherapy.
* Patients must have at least 1 lesion positive on PSMA-PET, as defined by standard uptake value (SUV) ratio of tumor to liver greater than one.
* Patient can have any or no prior systemic therapies.
* At least 28 days must have elapsed between last anti-cancer treatment administration and the initiation of study treatment, or at least 5 half-lives of the prior systemic therapy must have elapsed (whichever is shorter).
* Patient must have resolution of all previous treatment related toxicities to CTCAE version 5.0 grade of ≤ 2.
* Patient must be ≥ 18 years of age.
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

For female patients with childbearing potential or male patients with partners of childbearing potential, agreement to use barrier contraceptive method (condom) and to continue its use for 6 months from receiving the last dose of 177Lu-PSMA. Female patients with childbearing potential will undergo a urine pregnancy test. Pregnant female participants are excluded.

* Patient must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Spinal cord compression or impending spinal cord compression.
* Suspected pulmonary and/or liver metastases (greater \>10 mm in largest axis).
* Unable to lie flat during or tolerate PET/CT.
* Refusal to sign informed consent.
* Any medical comorbidities that might preclude safe participation in the study.

Additional inclusion criteria only relevant if Cohort 2 participants enrolled:

* Adequate bone marrow reserve and organ function as demonstrated by complete blood count and chemistry panel completed within the prior 28 days demonstrating:

  1. Platelet count of \>100 x109/L
  2. White blood cell (WBC) count \> 3,000/mL
  3. Neutrophil count of \> 1,500/mL
  4. Hemoglobin ≥ 10 g/dL
  5. Estimated glomerular filtration rate (eGFR) \> 50 mL/min based upon Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Due to safety concerns relating to renal clearance and toxicity of 177Lu-PSMA, patients with estimated GFR between 50 - 60 mL/min will require a 99mTc-TPA GFR test and only patients with non-obstructive pathology will be included in the study.
  6. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤5 x upper limit of normal (ULN), total bilirubin \< 3 x ULN
  7. Total bilirubin \< 3 x ULN (except if confirmed history of Gilbert's disease)
  8. Serum albumin \> 30 g/L

Additional exclusion criteria only relevant if Cohort 2 participants enrolled:

* Inadequate bone marrow reserve and organ function as detailed in eligibility criteria.
* Patient is participating in a concurrent investigative treatment protocol involving radiotherapy, surgery, or systemic anti-cancer agents.
* Patient receiving any other investigational agents.