| Eligibility |
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, monoclonal
antibodies, other investigational agent) < 21 days prior to the first dose of study
drug.
- Mean QT interval corrected for heart rate (QTc) >/= 470 ms calculated from 3
electrocardiograms (ECGs) using Fridericia's Correction
- Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or
systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
prednisone, or an equivalent corticosteroid. Steroid pre-medication for CT scan
contrast or study drug, is allowable, regardless of dose.
- Any prior Grade >/= 3 immune-related adverse event (irAE) while receiving any previous
immunotherapy agent, or any unresolved irAE > Grade 1
- Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects
with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
the past 2 years) are not excluded.
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
ulcerative colitis)
- History of primary immunodeficiency
- History of allogeneic organ transplant
- History of hypersensitivity to durvalumab or any excipient
- History of hypersensitivity to TPIV200
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diatheses including any subject known to have evidence of acute or chronic
hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric
illness/social situations that would limit compliance with study requirements or
compromise the ability of the subject to give written informed consent
- Known history of previous clinical diagnosis of tuberculosis
- Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab
- Subjects who are pregnant, breast-feeding or of reproductive potential who are not
employing an effective method of birth control
- Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results
- Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results
- Subjects with uncontrolled seizures
- Known hypersensitivity reaction to the GM-CSF adjuvant
- Patients who have developed any evidence of clinical or radiologic pneumonitis,
COP/BOOP, or other lung injury, during treatment with prior FRa-targeting therapy,
such as mirvetuximab soravtansine (IMGN853), or with any prior cancer immunotherapy.
|
