Human Epidermal Growth Factor Receptor 2 Fresh Peripheral Blood Mononuclear Cells for the Treatment of Metastatic Castrate Resistant Prostate Cancer and Metastatic Breast Cancer

Inclusion Criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Age ≥ 18 years at the time of signing informed consent
• Expected survival ≥ 3 months in the judgment of the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Absolute lymphocyte count ≥ 400/mm^3 (within 10 days of study registration)
• Absolute neutrophil count (ANC) ≥ 1,000/mm^3 (within 10 days of study registration)
• Platelets ≥ 75,000/mm^3 (within 10 days of study registration)
• Hemoglobin ≥ 9 g/dL (within 10 days of study registration)
• Serum creatinine < 2.0 mg/dl OR measured or calculated creatinine clearance ≥ 50 ml/mm (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) (within 10 days of study registration) * Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin ≤ 2 mg/dl (biliary stent is allowed) (within 10 days of study registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) < 5.0 times normal (within 10 days of study registration)
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) < 5.0 times normal (within 10 days of study registration)
• Agreement to adhere to Lifestyle Considerations throughout study duration
• A diagnosis of either of the following: * Prostate cancer ** Histological and/or cytological confirmation of prostate adenocarcinoma ** Participants must have progressive mCRPC at screening. Progression will be based on one of the following criteria: *** Serum/plasma prostate-specific antigen (PSA) progression defined as two consecutive increases in PSA (> 25%) over a previous reference value measured at least 1 week prior. The minimal start value is 1.0 ng/mL (a minimum PSA 2.0 ng/mL is required for participants without measurable disease by Response Evaluation Criteria in Solid Tumors [RECIST] version [v] 1.1 at screening.) *** Soft tissue progression defined as an increase ≥ 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for nonmodal lesions) of all target lesions based on the smallest SOD since beginning of most recent treatment on which the participant progressed or the appearance of one or more new lesions *** Bone disease progression with evaluable disease or new bone lesions by bone scan per Prostate Cancer Working Group 3 (PCWG3) criteria ** Serum testosterone levels < 50 ng/dL during screening. Participants without a prior bilateral orchiectomy are required to remain on luteinizing hormone release hormone (LHRH) analog to maintain castrate levels of testosterone during the course of study participation ** Must have progressed on at least one prior androgen receptor pathway inhibitor (ARPI) (abiraterone acetate, enzalutamide, apalutamide, or darolutamide) ** Participants must have ≥ 1 metastatic lesion that is present on baseline computed tomography (CT), magnetic resonance imaging (MRI), or bone scan obtained ≤ 28 days prior to registration * Breast cancer ** Histological and/or cytological confirmation of invasive breast cancer. Any receptor combination is permitted (estrogen receptor [ER]/progesterone receptor [PR]/HER2 positive, negative, low or ultralow is permitted) ** Participants must have previously treated metastatic breast cancer at screening. Metastatic breast cancer must be evaluable by RECIST 1.1 criteria. Evaluable metastatic breast cancer could entail: *** Soft tissue disease lesion measuring at least 1.0 cm in longest diameter or a lymph node measuring at least 1.5 cm in short axis *** Bone metastases with evaluable disease by CT, positron emission tomography (PET) or bone scan *** Cutaneous-only disease may be evaluable if discrete lesions are present. Skin lesions that are predominantly ulcerated (> 50% ulcerated) are not evaluable **** Note: Diffuse lymphangitic disease (without a discrete mass) of the lung, liver, brain or peritoneum will not be considered evaluable for this study ** Must have progressed on at least two prior endocrine or targeted therapies or at least two lines of cytotoxic chemotherapy. If HER2 positive, then must have progressed on or been intolerant of at least one HER2 targeted therapy. Target therapies include CDK4/6 inhibitors, mammalian target of rapamycin (mTOR) inhibitors, PI3KCA inhibitors, Poly (ADP-Ribose) polymerase (PARP) inhibitors and any genomic targeted agent (such as a BRAF, NTRK, ROS or other inhibitor). An aromatase inhibitor, selective estrogen receptor degrader (SERD) or tamoxifen as a single agent will count as a line of therapy. Antibody drug conjugates will be counted as cytotoxic chemotherapy (including ado-trastuzumab, trastuzumab deruxtecan, sacituzumab govitecan, datopotomab deruxtecan) ** Participants must have ≥1 metastatic lesion that is present on baseline CT, MRI, or bone scan obtained ≤ 28 days prior to registration

Exclusion Criteria

• Pregnancy (must have negative pregnancy test within 7 days prior to study registration) or lactation
• History of a recent myocardial infarction (within one year) or a past myocardial infarction (more than one year prior to enrollment) who are actively requiring nitroglycerine more than once per week
• Inadequate cardiac function, as defined as any of the following: * Uncontrolled angina or severe ventricular arrhythmias * Clinically significant pericardial disease * History of myocardial infarction (MI) in the last year before registration * Class 3 or higher New York Heart Association congestive heart failure
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study registration. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to registration
• Active liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
• Is HIV positive or has evidence of active hepatitis C virus or active hepatitis B virus
• Active bleeding or a pathological condition that is associated with a high risk of bleeding (therapeutic anticoagulation is allowed)
• Has an active infection requiring systemic therapy
• A serious uncontrolled medical disorder that in the opinion of the Investigator may be jeopardized by the treatment with protocol therapy
• Has a known history of active TB (Bacillus tuberculosis)
• Has received a live vaccine within 30 days of study registration
• Treatment with any investigational agent within 3 weeks prior to study registration
• Active second malignancy requiring systemic treatment. Exceptions include basal cell carcinoma of the skin, treated cervical cancer, and squamous cell carcinoma of the skin
• Has active autoimmune disease that has required systemic treatment in the 2 years prior to registration (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient’s participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
• Patient may be excluded if, in the opinion of the principal investigator (PI) and investigator team, the patient is not capable of being compliant
• Additional exclusion criteria for patients with prostate cancer: Has small cell neuroendocrine carcinoma (pure or mixed) on prior or current histologic evaluation of primary or metastatic lesions
• Additional exclusion criteria for patients with prostate cancer: Has an actionable BRCA1 or BRCA2 alteration, for which approved therapies are available, e.g., PARP inhibitors, unless these therapies are not appropriate for the participant as determined by the investigator or the participant refuses such therapy. Participants with one of these mutations and who have progressed on targeted therapy are eligible
• Additional exclusion criteria for patients with breast cancer: Has an actionable BRCA1 or BRCA2 alteration, for which approved therapies are available, e.g., PARP inhibitors, unless these therapies are not appropriate for the participant as determined by the investigator or the participant refuses such therapy. Participants with one of these mutations and who have progressed on targeted therapy are eligible
• Additional exclusion criteria for patients with breast cancer: Participants in visceral crisis at risk of immediately life-threatening complications in the short term, including participants with massive uncontrolled effusions (pleural, pericardial, and peritoneal), pulmonary lymphangitis, or liver involvement > 50%