Peptide Alarm Therapy with PD-1/PD-L1 Inhibitor for the Treatment of Patients with Metastatic or Locally Advanced Refractory Solid Cancers

Inclusion Criteria

• PRE-SCREENING FOR EPSTEIN-BARR VIRUS (EBV) AND CYTOMEGALOVIRUS (CMV) ANTIBODY STATUS: Diagnosis of a solid tumor cancer (except brain) that has failed to be controlled after prior therapy. To be eligible the patient must have failed prior treatment with a PD-1/PD-L1 inhibitor. Enrolling after one line of therapy is permitted provided this therapy included a PD-1/PD-L1 inhibitor and the patient is ineligible for or refuses 2nd line therapy.
• PRE-SCREENING FOR EBV AND CMV ANTIBODY STATUS: Have at least two accessible tumors with a >= 1.5 cm in longest diameter and distinct borders. For the dose finding component, the tumor at least 1 tumor must be superficial (cutaneous, subcutaneous or nodal); otherwise tumors may be superficial or visceral.
• PRE-SCREENING FOR EBV AND CMV ANTIBODY STATUS: Appears to meet study inclusion/exclusion criteria by review of medical record.
• PRE-SCREENING FOR EBV AND CMV ANTIBODY STATUS: Age 18 years or older at the time of signing the pre-screening consent.
• PRE-SCREENING FOR EBV AND CMV ANTIBODY STATUS: Voluntary written consent to collect blood for pre-screening testing (EBV and CMV status and if EBV+ and CMV+, HLA testing).
• DISEASE RELATED CRITERIA: Metastatic/locally advanced solid tumor malignancy (except brain) that has progressed on or is refractory to at least one prior therapy. Prior therapy must have included treatment with a PD-1/PD-L1 inhibitor. Enrolling after one line of therapy is permitted provided this therapy included a PD-1/PD-L1 inhibitor and the patient is ineligible for or refuses 2nd line therapy.
• DISEASE RELATED CRITERIA: Have at least two accessible tumors for biopsy that meet Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST) for measurable disease: one for biopsy/injection of the PAT (target) and one for biopsy only (control) to follow for abscopal effect. The interventional radiology (IR) team will assist in identifying the targeted tumors (one for injection, one as a control), as the tumor biopsies and the PAT injection are done in IR. * Each tumor must be >= 1.5 cm in longest diameter and have distinct borders based on exam or imaging * The tumor for PAT injection must be located in an anatomic location where the peptide can be safely administered, i.e., not encasing/in close proximity to crucial structures (carotid artery, jugular vein, trachea, etc.) * For the dose finding component, the tumor for injection must be visible/superficial (cutaneous, subcutaneous or nodal); otherwise the tumors may be superficial or visceral.
• DISEASE RELATED CRITERIA: Qualifies for treatment with a diagnosis appropriate PD1/PD-L1 inhibitor. For the dose finding component only the participant must qualify for treatment with pembrolizumab. According to the Keytruda 2021 United States Prescribing Information (USPI) the following tumor types were an Food and Drug Administration (FDA) approved indication for pembrolizumab – refer to the current Keytruda USPI for disease specific information: * Melanoma * Non-small cell lung cancer - if EGFR or ALK rearranged non-small cell lung cancer (NSCLC), then only after failure of all FDA-approved TKI and prior immunotherapy would be eligible * Head and neck carcinoma * Urothelial carcinoma * Gastric cancer * Esophageal cancer * Cervical cancer * Renal cell carcinoma * Endometrial cancer * Cutaneous squamous cell carcinoma * Triple negative breast cancer * Merkel cell cancer * Hepatocellular carcinoma * Any microsatellite instability (MSI)-high/mismatch repair protein deficient (MMRD) solid tumor
• Must have at least one HLA-A*0201 allele. HLA testing on blood is done after CMV and EBV seropositivity is established as part of the pre-screening process. If available, the results of previous tumor profiling by any Clinical Laboratory Improvement Act (CLIA)- certified lab (i.e. Caris, FoundationOne) may be used in lieu of HLA testing.
• 18 years or older at the time of signing the pre-screening consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 14 days of day 1).
• Platelets >= 100 x 10^9/L unsupported by transfusion (within 14 days of day 1).
• Hemoglobin >= 10 g/dL, independent of transfusion =< 14 days of screening (within 14 days of day 1).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN); if liver metastases, then =< 5 x ULN (within 14 days of day 1).
• Total bilirubin =< 1.5 x ULN; < 2 x ULN if hyperbilirubinemia is due to Gilbert’s syndrome (within 14 days of day 1).
• Serum albumin >= 3.0 g/dL (within 14 days of day 1).
• Serum creatinine =< 1.5 x ULN; OR estimated glomerular filtration rate (eGFR) >= 45 mL/min using the Cockcroft Gault formula (within 14 days of day 1).
• International normalized ratio (INR) or prothrombin time (PT)/partial thromboplastin time (PTT): =< 1.5 x ULN (within 14 days of day 1).
• Pulmonary function: oxygen saturation >= 90% on room air. If symptomatic or prior known impairment, pulmonary function >= 50% corrected diffusion capacity of the lung for carbon monoxide (DLCO) and forced expiratory volume in 1 second (FEV1) is required.
• Cardiac Function: New York Heart Association (NYHA) Functional Classification class I.
• Time between last dose of prior anti-cancer therapy and day 1 of this study: * Chemotherapy: a minimum of 28 days since last treatment. * Targeted therapy, immunotherapy, investigational agents: a minimum of 45 days since last dose (at least 2 months for anti-VEGF). * Prior palliative radiotherapy within 7 days of start of study treatment. Participants must have recovered from all radiation-related toxicities (prior irradiation to targeted lesions is not permitted).
• Must have recovered to CTCAE =< grade 1 from previous treatment related toxicity except alopecia.
• Persons of childbearing potential or with partners of childbearing potential must be willing to abstain from heterosexual activity or use a highly effect form of contraception from the time of study enrollment until at least 120 days after the last dose of PD-1/PD-L1 inhibitor. Persons are considered of childbearing potential unless: they are postmenopausal; are surgically sterile; or they have a congenital or acquired condition that prevents childbearing. NOTE: Abstinence is acceptable if this is the usual lifestyle and preferred contraception.
• Able to understand and provide voluntary written consent prior to the performance of any research related activity.

Exclusion Criteria

• Pregnant or breast feeding – persons of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to study enrollment – it must be repeated and negative within 72 hours of the 1st dose of the PD-1/PD-L1 agent.
• Requires therapeutic anticoagulation for which it is deemed unsafe to discontinue anticoagulation for 5 days prior to cycle 1 through day 7 of cycle 1.
• Class II or greater New York Heart Association Functional Classification criteria or serious cardiac arrhythmias likely to increase the risk of cardiac complications of therapy (e.g. ventricular tachycardia, frequent ventricular ectopy, or supraventricular tachyarrhythmia requiring chronic therapy).
• Known active central nervous system (CNS) metastases.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (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.
• History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist [registered trademark]) are live attenuated vaccines and are not allowed.
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to study enrollment.
• Prior bone marrow and/or solid organ transplant.
• Has severe hypersensitivity (>= grade 3) to prior PD-1/PD-L1 and/or any of its excipients.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Known seropositive for human immunodeficiency virus (HIV) or known active hepatitis B or C infection with detectable viral load by polymerase chain reaction (PCR).
• Known history of active TB (Bacillus Tuberculosis).
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 45 days prior to the first dose of study treatment.
• Has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements in the opinion of the treating investigator.