The study is a non-randomized, open-label phase II clinical trial to test the investigational
combination of the drug pembrolizumab with the drug olaparib in patients diagnosed with
advanced or recurrent cervical carcinoma after standard chemotherapy.
1. Female participants who are at least 18 years of age on the day of signing informed
consent with histologically confirmed diagnosis of cervical carcinoma will be enrolled
in this study.
2. Cervical cancer is a disease of the female genital tract. No male patients will be
3. A female participant is eligible to participate if she is not pregnant (see Appendix
3), not breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the
treatment period and for at least 120 days after the last dose of study
4. Participant must have recurrent cervical cancer and have a low potential for cure with
radiation therapy or surgery alone and:
a. May have received up to 2 prior chemotherapy regimens. Platinum sensitizing agents
for radiation therapy are considered a chemotherapy regimen.
5. The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial, which includes compliance with the requirements and
restrictions listed in the informed consent form (ICF) and this protocol.
6. Have measurable disease based on RECIST 1.1. Lesions situated in a previously
irradiated area are considered measurable if progression has been demonstrated in such
7. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy
of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE)
tissue blocks are preferred to slides. Newly obtained biopsies are preferred to
8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Evaluation of ECOG is to be performed prior to the first dose of treatment.
9. Patient's life expectancy ≥ 16 weeks.
10. Have adequate organ function as defined in the following table (Table 1). Specimens
must be collected within 10 days prior to the start of study treatment. Before
patients can be enrolled, they must have normal laboratory values as outlined in Table
1. Labs must also fall within normal limits prior to infusion.
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to the first
dose of treatment (see Appendix 3). If the urine test is positive or cannot be
confirmed as negative, a serum pregnancy test will be required.
2. Note: in the event that 72 hours have elapsed between the screening pregnancy test and
the first dose of study treatment, another pregnancy test (urine or serum) must be
performed and must be negative in order for subject to start receiving study
3. 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).
4. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks prior to the first dose of treatment.
5. Has received prior radiotherapy within 2 weeks of start of study intervention.
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.
6. Has received a live vaccine within 30 days prior to the first dose of study drug.
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.
7. 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 first dose of
8. Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin,
clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg.
ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout
period prior to starting olaparib is 2 weeks.
9. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin,
rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or
moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout
period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3
weeks for other agents.
10. Major surgery within 2 weeks of starting study treatment and patients must have
recovered from any effects of any major surgery.
11. 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 first dose of study drug.
12. Has a history of a second malignancy, unless potentially curative treatment has been
completed with no evidence of malignancy for ≥5 years except: adequately treated
non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal
carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma.
13. 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
first dose of study intervention.
Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence
of brain metastases is not required. The patient can receive a stable dose of
corticosteroids before and during the study as long as these were started at least 4
weeks prior to treatment. Patients with spinal cord compression unless considered to
have received definitive treatment for this and evidence of clinically stable disease
for 28 days.
14. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients,
or patients with a known hypersensitivity to olaparib or any of the excipients of the
15. 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 is allowed.
16. Has a history of (non-infectious) pneumonitis that required steroids or has current
17. Has an active infection requiring systemic therapy.
18. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV
testing is required unless mandated by local health authority. Immunocompromised
patients, e.g., patients who are known to be serologically positive for human
immunodeficiency virus (HIV), solid organ, and hematopoietic transplant patients.
19. 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
20. Has a known history of active TB (Bacillus Tuberculosis).
21. 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.
Patients considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection. Examples
include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3
months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal
cord compression, superior vena cava syndrome, extensive interstitial bilateral lung
disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder
that interferes with the requirements of the trial or prohibits obtaining informed
22. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
23. Is pregnant or breastfeeding or expecting to conceive children within the projected
duration of the study, starting with the screening visit through 120 days after the
last dose of trial treatment.
24. Has had an allogenic tissue/solid organ/bone marrow transplant or double umbilical
cord blood transplantation (dUCBT).
25. Resting ECG and EKG 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 patients with congenital long QT syndrome.
26. Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) V. 5.0
grade 2) caused by previous cancer therapy, excluding alopecia.
27. Patients with myelodysplastic syndrome/acute myeloid leukemia or with features
suggestive of Myelodysplastic syndromes and acute myeloid leukemia (MDS/AML).
28. Patients unable to swallow orally administered medication and patients with
gastrointestinal disorders likely to interfere with absorption of the study
29. Whole blood transfusions in the last 120 days prior to entry to the study (packed red
blood cells and platelet transfusions are acceptable).