Lamivudine with Standard of Care Anti-PD-L1 Blockade for the Treatment of Patients with Relapsed or Refractory Unresectable Solid Tumors

Inclusion Criteria

• Patients must have a pathologically confirmed diagnosis of a solid malignancy
• Patients must have progressed (clinically or radiographically) on or following prior therapy with a PD-1 or PD-L1 targeted antibody
• Patients must have exhausted or declined all standard therapies deemed to have significant clinical benefit
• Patients may have only 0 or 1 intervening lines of therapy from the prior PD-(L)1 blocking therapy
• Patient must be willing and able to provide blood samples (12 green-top tubes, roughly 100mL) at the four time points indicated in the study calendar
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) 0-2. The exception will be patients carrying long term disability (such as cerebral palsy) where the disability is not acute nor progressive, and unlikely to significantly affect their response to therapy. This must be documented in screening clinic visit note by investigator
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 3 months following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 24 consecutive months
• Ability to understand and the willingness to sign a written informed consent
• Absolute neutrophil count (ANC) ≥ 1,000 /mcL
• Platelets ≥ 75,000 /mcL
• Hemoglobin ≥ 9 g/dL
• Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) ≤1.5 X upper limit of normal (ULN) OR ≥ 60 mL/min for patient with creatinine levels > 1.5 X institutional ULN * Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN ≤ 3 X ULN for patients with liver metastases * If laboratory criteria are not met due to what the investigator determines to be a biologic cause (e.g. Gilbert’s syndrome causing elevated bilirubin or excessive muscle mass affecting creatinine) or drug-related cause (e.g. elevating in transaminases due to highly active antiretroviral therapy [HAART] therapy, elevated international normalized ratio [INR] due to anticoagulation) then the specific lab values will not be used to exclude patient from this trial. This determination will be made by principal investigator (PI)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 X ULN OR ≤ 5 X ULN for patients with liver metastases. * If laboratory criteria are not met due to what the investigator determines to be a biologic cause (e.g. Gilbert’s syndrome causing elevated bilirubin or excessive muscle mass affecting creatinine) or drug-related cause (e.g. elevating in transaminases due to HAART therapy, elevated INR due to anticoagulation) then the specific lab values will not be used to exclude patient from this trial. This determination will be made by PI
• Albumin > 2.5 mg/dL * If laboratory criteria are not met due to what the investigator determines to be a biologic cause (e.g. Gilbert’s syndrome causing elevated bilirubin or excessive muscle mass affecting creatinine) or drug-related cause (e.g. elevating in transaminases due to HAART therapy, elevated INR due to anticoagulation) then the specific lab values will not be used to exclude patient from this trial. This determination will be made by PI

Exclusion Criteria

• Patients who have had chemotherapy within 14 days from start of therapy
• Patients who have had radiotherapy within 7 days from start of therapy, though exception may be made for palliative radiotherapy which is permitted at anytime, if deemed in the best interest of the patient
• Patients may not be receiving any other investigational agents
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring antibiotics (exception is a brief [≤ 10 days] course of antibiotics to be completed before initiation of treatment), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Exception: Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10 mg prednisone will not be excluded
• Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Exception: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is acceptable
• 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
• Known HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen, or with < 350 CD4+ T cells/microliter in the peripheral blood. HIV testing is mandatory since the diagnosis of cancer for patients with no known history of HIV. For such patients HIV testing will be considered standard of care (SOC)
• Any patient already on antiretroviral therapy
• Has known hepatitis B or active hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected). Hepatitis B virus (HBV) and HCV testing is mandatory since the diagnosis of cancer for patients with no known history of these viruses. For such patients HBV and HCV testing will be considered SOC
• History of allogeneic hematopoietic cell transplantation or solid organ transplantation
• Receipt of a live vaccine within 30 days of planned start of study drug
• Documented allergic or hypersensitivity response to any protein therapeutics (e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies, receptor traps). Principal investigator believes that for one or multiple reasons the patient will be unable to comply with all study visits, or if they believe the trial is not clinically in the best interest of the patient
• History of immune related adverse event (irAE) in response to prior immunotherapy that has not improved to a grade 0 or 1; this does not include chronic conditions such as endocrinopathies which can be treated with hormone replacement therapy
• History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis attributed to prior use of cancer immunotherapy that required immune-suppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted