| Eligibility |
Inclusion Criteria:
1. Be able and willing to provide written and signed informed consent prior to performing
any protocol-related procedures, including screening evaluations.
2. Women, 18 years or older, with stage III / IV platinum-refractory Ovarian Cancer (OC)
(progressed on a platinum containing regimen within 6 months of therapy and
adenocarcinoma histology) that can be evaluable by RECISTv1.1 criteria who progressed
on standard treatment. Participants will be recruited irrespective of if they earlier
received available FDA-approved therapies (including for participants with targetable
mutations, such as BRCA mutations)
3. Subjects will be eligible for study entry based on the following diagnostic workup:
1. History/physical examination within 28 days prior to registration.
2. Imaging of target lesion(s) within 28 days prior to registration.
3. Study-specific assessments:
4. Recovery from effects of recent surgery, radiotherapy or chemotherapy.
5. Free of active infection requiring antibiotics (with the exception of
uncomplicated urinary tract infection).
6. Any hormonal therapy directed at the malignant tumor must be discontinued at
least one week prior to registration.
7. Any other prior therapy directed at the malignant tumor including chemotherapy,
targeted agents, biologic agents, immunologic agents, and any investigational
agents, must be discontinued at least 4 weeks prior to registration (6 weeks for
nitrosoureas or mitomycin C).
8. Any prior radiation therapy must be completed at least 4 weeks prior to
registration.
9. At least 4 weeks must have elapsed since major surgery.
4. Subjects must have received and have progressed, are refractory, or are intolerant to
standard platinum therapy. Subjects should not have received more than 2 prior lines
of systemic therapy for recurrent or metastatic disease (including both standard of
care and investigational therapies).
5. Subjects must have at least 1 lesion that is measurable using RECIST Version 1.1
guidelines.
1. A previously irradiated lesion can be considered a target lesion if the lesion is
well defined, measurable per RECIST Version 1.1, and has clearly progressed.
2. Subjects undergoing fresh tumor biopsies must have additional non-target lesions
that can be biopsied at acceptable risk as judged by the investigator (optional).
6. Subjects must consent to provide archived tumor specimens for correlative biomarker
studies. Tumor tissue must be identified and availability confirmed prior to
initiation of study therapy. In the setting where archival material is unavailable or
unsuitable for use, subjects must consent and undergo fresh tumor biopsy.
7. All subjects are encouraged to consent to and provide both pretreatment and
on-treatment (optional) tumor biopsies.
8. Eastern Cooperative Oncology Group (ECOG) Performance score of 2 or less.
9. In the opinion of the investigator likely to complete = 8 weeks of treatment.
10. Adequate organ function as determined by:
a) Hematological: i) Absolute neutrophil count (ANC) = 1.0 × 109/L (1,000/mm3) ii)
Absolute lymphocyte count (ALC) = 0.5 × 109/L (500/mm3) iii) Platelet count = 100 ×
109/L (100,000/mm3) without transfusion support within first 2 weeks prior to first
dose iv) Hemoglobin = 9.0 g/dL without transfusion support within first 2 weeks prior
to first dose b) Renal: i) Calculated creatinine clearance* (CrCl) or 24-hour urine
CrCl > 50 mL/minute c) Hepatic: i) Total bilirubin = 1.5 × upper limit of normal
(ULN); for subjects with documented/suspected Gilbert's syndrome, bilirubin = 3 × ULN
ii) Aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 × ULN (AST
and/or ALT can be up to 5 × ULN in the presence of liver metastasis, but cannot be
associated with concurrent elevated bilirubin)
11. Female subjects of childbearing potential who are sexually active with a nonsterilized
male partner must use at least 1 highly effective method of contraception from
screening, and must agree to continue using such precautions for 180 days after the
final dose of investigational product. The male partner of the female subject must use
male condom plus, if locally available, spermicide throughout this period. Cessation
of contraception after this point should be discussed with a responsible physician.
Not engaging in sexual activity for the duration of the study is an acceptable
practice; however, periodic abstinence, the rhythm method, and the withdrawal method
are not acceptable methods of contraception.
1. Females of childbearing potential are defined as those who are not surgically
sterile (i.e., have not undergone bilateral tubal ligation, bilateral
oophorectomy, or complete hysterectomy) or who are not postmenopausal (defined as
12 months with no menses without an alternative medical cause).
2. A highly effective method of contraception is defined as one that results in a
low failure rate (i.e., less than 1% per year) when used consistently and
correctly.
3. Subjects must refrain from breastfeeding while on study and for 180 days after
the final dose of investigational product.
Exclusion Criteria:
1. Subjects who have received prior therapy with regimens containing nivolumab or CTLA-4,
PD-L1, PD-L2 or PD-1 antagonists or any other antibody or drug specifically targeting
T cell co-stimulation or immune checkpoint pathways.
2. Any condition that, in the opinion of the investigator, would interfere with
evaluation of the investigational product or interpretation of subject safety or study
results.
3. History of severe allergic reactions (i.e., Grade 4 allergy, anaphylactic reaction
from which the subject did not recover within 6 hours of institution of supportive
care) to any unknown allergens or any components of the study drug formulations.
4. Active or prior documented autoimmune disease (including inflammatory bowel disease,
celiac disease, Wegener's granulomatosis) within the past 2 years. Subjects with
childhood atopy or asthma, vitiligo, alopecia, Graves disease, Hashimoto disease,
autoimmune diseases that will be consider stable by hormones /steroid replacement or
psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
5. Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study or the follow-up period of an interventional
study.
6. Receipt of any conventional or investigational anticancer therapy not otherwise
specified above within 28 days prior to the first dose of the combination treatment;
in the case of monoclonal antibodies, 28 days or 5 half-lives, whichever is shorter,
prior to the first dose of the combination treatment.
7. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer
treatment. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin
for diabetes and hormone replacement therapy) is acceptable.
8. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to
NCI CTCAE V5.0, Grade 0 or 1 with the exception of alopecia and laboratory values
listed per the inclusion criteria. Subjects with irreversible toxicity that is not
reasonably expected to be exacerbated by any of the investigational products may be
included (e.g., hearing loss)
9. Current or prior use of immunosuppressive medication within 14 days prior to the first
dose of any treatment regimen. The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g.,
intra-articular injection)
2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or equivalent
3. Steroids as premedication for hypersensitivity reactions (e.g., computerized
tomography (CT) scan premedication)
10. History of primary immunodeficiency, solid organ transplantation, or tuberculosis.
11. Test results indicating active infection with hepatitis B or C defined by positive
Hepatitis B DNA, Hepatitis C RNA or known HIV infection.
12. Receipt of live, attenuated vaccine within 28 days prior to the first dose of
investigational products (NOTE: Subjects, if enrolled, should not receive live vaccine
during the study and 180 days after the last dose of investigational products).
13. Pregnant or breastfeeding women.
14. Major surgery (as defined by the investigator) within 4 weeks prior to first dose of
treatment regimen, or still recovering from prior surgery. Local surgery of isolated
lesions for palliative intent is acceptable.
15. Other invasive malignancy within 2 years except for noninvasive malignancies such as
cervical carcinoma in situ, non-melanomatous carcinoma of the skin, ductal carcinoma
in situ of the breast or non invasive bladder carcinoma that has/have been surgically
removed.
16. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, unstable angina pectoris, history of myocarditis, myocardial infarction =6
months, or congestive heart failure (as defined by New York Heart Association
Functional Classification III or IV) requiring use of ongoing maintenance therapy for
life-threatening ventricular arrhythmias, or psychiatric illness/social situations
that would limit compliance with study requirement, substantially increase risk of
incurring adverse events or compromise the ability of the subject to give written
informed consent. In addition, participants with a left ventricular ejection fraction
(LVEF) < 50% by echocardiogram will be excluded.
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