TPIV200/huFR-1 (A Multi-Epitope Anti-Folate Receptor Vaccine) Plus Anti-PD-L1 MEDI4736 (Durvalumab) in Patients With Platinum Resistant Ovarian Cancer

Inclusion Criteria

• Subjects must have recurrent or persistent platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with measureable disease (as defined by RECIST 1.1.) who have received at least one prior platinum-based therapy.

Platinum-based therapy is defined as treatment with carboplatin, cisplatin or another organoplatinum compound.

Platinum-resistant is defined as having had disease progression within 6 months or most recent platinum therapy, or having disease progression while receiving previous platinum-based chemotherapy.

Histologic documentation of diagnosis of carcinoma is required and the following histologic subtypes are eligible: high grade serous, clear cell, endometrioid, carcinoma, adenocarcinoma, mixed (including above subtypes only).

• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Resolution of (non-laboratory) adverse effects of recent surgery, radiotherapy, or chemotherapy to Grade ≤1 prior to first study treatment (with the exception of alopecia or neuropathy; chemotherapy-induced peripheral neuropathy up to Grade ≤2 will be permitted)
• Patients must have measurable disease. Measurable disease is defined by RECIST (version 1.1). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and has not been previously irradiated. Each lesion must be ≥ 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or ≥ 20 mm when measured by chest x-ray. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI.
• Adequate normal organ and marrow function defined by the following laboratory results obtained within 14 days prior to first treatment:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (> 1500 per mm3)
• Platelet ≥ 100 x 10^9/L (>100, 000 per mm3)
• Hemoglobin ≥ 9.0 g/dL
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). (Unless Gilbert's Syndrome, without concurrent clinically significant liver disease)
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
• Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:

Creatinine CL = Weight (kg) x (140 - Age) x 0.85 (mL/min) 72 x serum creatinine (mg/dL)

• Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
• Subject is 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.

Exclusion Criteria

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site); Previous enrollment in the present study.
• Participation in another clinical study with receipt of an investigational product during the last 4 weeks
• Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease (eg, cervical cancer in situ)
• Adequately treated stage 1 breast or stage 1 low grade endometrial cancer
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization,