Patients with pre neoplastic high grade HPV-related vulvar and cervical lesions MedDRA version: 20.0 Level: PT Classification code 10054932 Term: Vulvar dysplasia System Organ Class: 10038604 - Reproductive system and breast disorders MedDRA version: 20.0 Level: PT Classification code 10008263 Term: Cervical dysplasia System Organ Class: 10038604 - Reproductive system and breast disorders
Conditions
Interventions
Product Name: pembrolizumab
Product Code: [MK-3475]
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: NA
Concentration unit:
Sponsors
FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of cervical HSIL OR vulvar VIN 2-3 lesions will be enrolled in this study. - A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 3 months after the last dose of study treatment. - The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. - Have provided archival tumor tissue sample (if pre treatment biopsy performed at other institution) or newly obtained core or excisional biopsy of the 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. - 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 registration . - 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to study drug treatment. 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 systemic anti-cancer therapy including investigational agents within 4 weeks 4. Has received prior radiotherapy within 2 weeks of start of study treatment. 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. 5. 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. 6. 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 study treatment. 7. 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. 8. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. 9. 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. 10. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients. 11. 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. 12. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. 13. Has an active infection requiring systemic therapy. 14. Has a known history of Human Immunodeficiency Virus (HIV). 15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as qualitative HCV RNA is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. 16. Has a known history of active TB (Bacillus Tuberculosis). 17. 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 in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of Pembrolizumab in leading histopathologic complete regression of cervical HSIL;Secondary Objective: 1.To determine the efficacy of Pembrolizumab in leading histopathologic complete regression of vulvar VIN 2-3 lesions 2.To evaluate the safety and tolerability of Pembrolizumab in patients with HPV-related pre-neoplastic vulvar and cervical lesions 3.To determine Pembrolizumab efficacy as measured by histopathologic any grade regression of cervical and vulvar pre-neoplastic lesions 4.To determine Pembrolizumab efficacy in the virologic clearance of HPV 5.To determine Pembrolizumab efficacy as measured by histopathologic non-progression;Primary end point(s): Proportion of subjects with no evidence of cervical HSIL on histology at surgical treatment;Timepoint(s) of evaluation of this end point: 18 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportion of subjects with no evidence of vulvar VIN 2-3 on histology at surgical treatment; Incidence and severity of systemic events for the duration of the study (CTCAE version 5.0); Proportion of subjects with downstaging of cervical and vulvar pre-neoplastic lesion on histology; Proportion of patients with no evidence of HPV by HPV testing at Week 36 visit; Proportion of subjects with no progression of cervical HSIL and vulvar VIN 2-3 to cervical and vulvar carcinoma respectively from baseline on histology; Exploratory end points: 1.Evaluation may involve but are not limited to levels of serum anti-HPV antibody concentrations at baseline, Week 21 and at week 36 , Interferon-¿ ELISpot response magnitudes at baseline, Weeks 21 and 36 visits, Flow Cytometry response magnitudes at baseline and Week 21 visits 2. Assessment of markers including but not limited to CD8+ and FoxP3+ infiltrating cells. Additional assessments may include visualization of Granulysin, Perforin, CD137, CD103 and PD-L1 in cervical and vulvar tissue as sample allows. Markers listed here may change as new relevant information becomes available;Timepoint(s) of evaluation of this end point: 18 months; 18 months; 18 months; 18 months; 18 months; 18 months | — |
Countries
Italy
Contacts
Public ContactDirezione Scientifica Policlinico A
Direzione Scientifica Policlinico A. Gemelli IRCCS
Outcome results
None listed