Patients with stage IB2-IIB cervical cancer will be treated with 3 cycles of neoadjuvant
Carboplatin-Paclitaxel chemotherapy (Carboplatin AUC 5 d1 q 21+ Paclitaxel 175 mg/mq d1 q
21)+ Pembrolizumab (200 mg flat dose every 3 weeks).
After 3 cycles of neo-adjuvant platinum-based chemotherapy patients non progressing will
undergo radical surgery.
After surgery, patients presenting with high risk factors (positive lymphnodes, positive
parametria, positive surgical margins or at least 2 of the following risk factor between
tumor diameter >3 cm, LVSI, stromal infiltration >1/3) will receive 3 cycles of adjuvant
Carboplatin-Paclitaxel chemotherapy + Pembrolizumab in combination and maintenance with
Pembrolizumab 200 mg every 3 weeks until progression or unacceptable toxicity or patient
consent withdrawal for up to 35 cycles.
1. Female participants who are at least 18 years of age on the day of signing informed
consent with histologically confirmed diagnosis of FIGO Stage IB2-IIB cervical cancer
will be enrolled in this study. Squamous, adenocarcinoma and adenosquamous histotypes
2. PDL1+>1% of cell by IHC evaluation in tumor cells
3. Eligible for carboplatin and paclitaxel chemotherapy in accordance with local
standards of care
4. 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 4 months after the end of treatment
5. The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial.
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. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are
preferred to slides. Newly obtained biopsies are preferred to archived tissue.
Note: If submitting unstained cut slides, newly cut slides should be submitted to the
testing laboratory within 14 days from the date slides are cut.
8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Evaluation of ECOG is to be performed within 7 days prior to the date of treatment
9. 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.
10. No previous systemic chemotherapy or radiation therapy for cervical cancer
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment
initiation (see Appendix 3). If the urine test is positive or cannot be confirmed as
negative, a serum pregnancy test will be required.
2. 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).
3. Has received prior radiotherapy within 2 weeks of start of study treatment for
palliative intent. Participants must have recovered from all radiation-related
toxicities, not require corticosteroids, and not have had radiation pneumonitis.
4. 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.
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 first dose of
Note: Participants who have entered the follow-up phase of an investigational study
may participate as long as it has been 4 weeks after the last dose of the previous
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 first dose of study drug.
7. Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma,
cervical cancer in situ) that have undergone potentially curative therapy are not
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
first dose of study treatment.
9. Has severe hypersensitivity (≥Grade 3) to Pembrolizumab 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.
11. Has a history of (non-infectious) pneumonitis that required steroids or has current
12. Has an active infection requiring systemic therapy.
13. Has a known history of Human Immunodeficiency Virus (HIV).
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 is detected)
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. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
18. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment.
19. History of cerebrovascular accident, pulmonary embolism or untreated grade 3 deep
venous thrombosis (DVT) within the past 6 months
20. NCI CTCAE (version 5.0) grade ≥2 enteritis
21. History of myocardial infarction, unstable angina, subarachnoid haemorrhage, stroke or
transient ischaemic attack within 6 months before first dose of study drug
22. Clinically significant active cardiovascular disease (e.g., New York Heart Association
class II or greater congestive heart failure [CHF], aortic aneurysm)
23. Serious cardiac arrhythmia requiring medication. This does not include asymptomatic
atrial fibrillation with controlled ventricular rate
24. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
recent arterial thrombosis) within 6 months before study enrolment
25. Pre-existing NCI CTCAE (version 5.0) grade ≥2 peripheral neuropathy