Pilot Study of Durvalumab and Vigil in Advanced Women's Cancers

Inclusion Criteria

• •Ability to understand and the willingness to sign a written informed consent document for tissue harvest
• •Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• •Histologically or cytologically confirmed diagnosis of women's cancer, inclusive, but not limited to breast, ovarian, fallopian tube, primary peritoneal, uterine, cervical, endometrial, that is locally advanced or metastatic for which the projected response rate to durvalumab is 15% or less.
• •Female patients age ≥ 18 years
• •No prior Vigil immunotherapy
• •Treatment-naïve or refractory (no response to checkpoints) / resistant (initial response but relapse) to PD-1 or PD-L1 inhibitor therapy
• •ECOG Performance Status ≤ 1
• •Estimated survival ≥ 6 months
• •Planned standard of care surgical procedure (e.g., tumor biopsy or palliative resection or thoracentesis) and expected availability of a cumulative mass of \~10-30 grams tissue ("golf-ball" size) or pleural fluid estimated volume ≥ 500mL (must be primary tap) for immunotherapy manufacture.
• •One lesion not previously irradiated nor intended for vaccine manufacture, which can be biopsied with minimal invasion and measurable at baseline as per RECIST 1.1 guidelines (performed prior to biopsy) or 2 lesions not previously irradiated nor intended for vaccine manufacture, one of which can be biopsied with minimal invasion and the other of which is measurable at baseline as per RECIST 1.1 guidelines. If the only such target lesion has previously been irradiated it must have shown unequivocal evidence of disease progression following completion of radiation therapy. Alternative methods of disease assessment, e.g. measurement of tumor markers or ascites/pleural fluid, may be considered by the Sponsor on a case-by-case basis.
• •Provision of tumor tissue sample (archived or fresh) to allow for PD-L1 expression analysis
• •Successful manufacturing of at least 4 vials of Vigil.
• •Ability to understand and the willingness to sign a written informed consent document
• •Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• •Estimated survival of ≥ 6 months
• •Provision of tumor tissue sample (archived or fresh) in a quantity sufficient to allow for PD-L1 expression analysis (if not already obtained during tissue procurement under this protocol), and after entry, a portion of Vigil harvested tissue
• •If female of childbearing potential, has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a negative serum test will be required for study entry. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, complete hysterectomy, or surgery for gynecological cancer) or postmenopausal (defined as 12 months with no menses without an alternative medical cause).
• •Adequate organ and bone marrow function as defined below:
• •1. Absolute neutrophil count (ANC) \> 1.5 × 10\^9/L (1500 per mm\^3)
• •2. Platelets \> 100 × 10\^9/L (100,000 per mm\^3)
• •3. Hemoglobin ≥ 9.0 g/dL (5.59 mmol/L)
• •4. Creatinine clearance (CrCL) \> 50 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance:
• •Females: CrCL (mL/min) = Weight (kg) × (140 - Age) × 0.85 / 72 × serum creatinine (mg/dL)
• •5. Serum bilirubin ≤ 1.5 × upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of hemolysis or hepatic pathology) who will be allowed in consultation with their physician.
• •6. AST and ALT ≤ 2.5 × ULN in patients with no liver metastasis
• •7. AST or ALT ≤ 5 × ULN in patients with liver metastasis
• •8. TSH within institutional limits. If TSH is greater or less than institutional limits patients may participate if their T4 is within normal limits (WNL); patients may be on a stable dose of replacement thyroid medication; dose adjustments are allowed if needed.
• •Subject has recovered to CTCAE Grade 1 or better from all adverse events associated with prior therapy or surgery
• •1. Pre-existing motor or sensory neurologic pathology or symptoms must be recovered to CTCAE Grade \> 2 or better
• •2. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by the IPs may be included (e.g., hearing loss) after consultation with the Medical Monitor
• •Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) prior to tissue procurement and at least 21 days prior to the first dose of study drug (at least 21 days prior to the first dose of study drug for subjects who have received prior TKIs \[e.g., erlotinib, gefitinib and crizotinib\] and within 6 week for nitrosourea or mitomycin C). (If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period may be required.)