| Eligibility |
Inclusion Criteria:
1. Participants who are at least 20 years of age on the day of signing informed consent
with histologically confirmed, recurrent or metastatic cervical cancer (squamous cell
carcinoma, adenocarcinoma or adenosquamous cell carcinoma)
2. Participants with confirmed disease progression during or after platinum-based
chemotherapy 1 or intolerant to or ineligible for platinum-based chemotherapy or
ineligible participants
3. Participants with measurable disease based on RECIST 1.1 at screening
4. Participant is able to provide a core or excisional biopsy of a tumor lesion for
testing of PD-L1 status, etc
5. Participants with Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1 upon the
screening
6. Participants who may be expected to survive at least for 12 weeks after the first dose
of study drug as determined by the principal investigator or a subinvestigator
7. Have adequate organ function
Exclusion Criteria:
1. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
OX-40, CD137).
2. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks prior to the enrollment.
3. Has received prior radiotherapy within 2 weeks prior to the enrollment. Participants
must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease.
4. Has received a live vaccine within 28 days prior to the enrollment. Examples of live
vaccines include, but are not limited to, the following: measles, mumps, rubella,
varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG),
and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed
virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®)
are live attenuated vaccines and are not allowed.
5. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the enrollment.
6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the enrollment.
7. Has a second malignancy advanced or requiring treatment within the past 3 years.The
time requirement does not apply to participants who underwent successful definitive
resection of basal cell carcinoma of the skin, in situ cancers (e.g. in situ breast
carcinomas).
8. Has known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days prior to the
enrollment.
9. Has severe hypersensitivity (=Grade 3) to the study drug and/or any of its excipients.
10. Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment and participants can be enrolled in the trial.
11. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
12. Has an active infection requiring systemic therapy.
13. Has a known history of Human Immunodeficiency Virus (HIV) infection.
14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection.
15. Has a known history of active TB (Bacillus Tuberculosis).
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
17. Participant has received colony-stimulating factors (eg, granulocyte colony
stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF]
or recombinant erythropoietin) within 2 weeks prior to the enrollment.
18. Participant with clinically serious cardiovascular/cerebrovascular diseases including
the following: cerebrovascular accident/stroke (less than 6 month prior to
enrollment), myocardial infarction (less than 6 month prior to enrollment), unstable
angina, congestive heart failure (the New York Heart Association (NYHA) Functional
Classification Class 2 or severer), or serious arrhythmia. In addition, participants
with history of bleeding tendency or recent major bleeding event in whom study drug
administration carries higher risks as determined by the principal investigator will
be excluded.
19. Participant who have acute or chronic disease with severe and/or clinical symptoms
which may compromise the tolerance to this study or competence to consistently follow
the study procedures as determined by the principal investigator
20. Participants with medical history of receiving all the PARP inhibitors
21. Participant is currently receiving either strong (eg, itraconazole, telithromycin,
clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg. ciprofloxacin,
erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450
(CYP)3A4 that cannot be discontinued before the study drug initiation. The required
washout period prior to starting olaparib is 2 weeks.
22. Participant is currently receiving either strong (eg, phenobarbital, enzalutamide,
phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine, and St
John's Wort) or moderate (eg. bosentan, efavirenz, modafinil) inducers of CYP3A4 that
cannot be discontinued before the study drug initiation. The required washout period
prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.
23. Participant is either unable to swallow orally administered medication or has a
gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel
obstruction, malabsorption).
24. Participant has resting electrocardiogram (ECG) indicating uncontrolled, potentially
reversible cardiac conditions, as judged by the investigator (eg, unstable ischemia,
uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500
ms, electrolyte disturbances, etc.), or participant has congenital long QT syndrome.
25. Has a major surgery history 4 weeks prior to the enrollment (e.g.: diagnostic biopsy
is not regarded as the major surgery)
26. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
27. Is pregnant or breastfeeding, or expecting to conceive children within the projected
duration of the study, starting with the screening visit within 120 days after the
last dose of trial treatment.
28. Participant, in the judgement of the investigator, is unlikely to comply with the
study procedures, restrictions, and requirements of the study.
29. Participant has had an allogenic tissue/solid organ transplant
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