Neo-adjuvant Pembrolizumab in Vulvar Squamous Cell Carcinoma: a Clinical Proof-of-concept Study
Status:
Not yet recruiting
Trial end date:
2025-02-01
Target enrollment:
Participant gender:
Summary
Rationale:
Vulvar squamous cell carcinoma (VSCC) is a rare cancer with a rising incidence. Standard
treatment comprises wide local excision of the primary tumour and inguinal lymph nodes and
sometimes (chemo) radiotherapy. Treatment is associated with impressive and long-lasting
morbidity, sexual and psychological dysfunction and wound healing disorders. Recurrent
disease develops in up to 40% of all treated patients. The unmet need, therefore, is a less
radical and more effective treatment for VSCC.
Hypothesis:
Based on the local immune profile in a large fraction of patients with primary VSCC the
investigators hypothesize that neoadjuvant PD-1 checkpoint inhibition may reinvigorate
tumor-specific T cells resulting in a reduced tumor load, potentially leading to less radical
surgery and reduces the recurrence rate.
The primary objectives of this trial are to study clinical efficacy and immune activation of
neoadjuvant PD-1 blockade in VSCC.
Study design: This is a prospective, multicenter phase II non-controlled clinical trial in 40
VSCC patients.
Study population: Clinically diagnosed FIGO I-III primary VSCC patients to be treated with
surgery with curative intent.
Intervention (if applicable):
Anti-PD1 antibody pembrolizumab, 200 mg IV Q3W for a total of 2 administrations per patient
over a period of 6 weeks prior to surgery.
Main study parameters/endpoints:
The primary endpoints are:
- Clinical efficacy of neoadjuvant PD-1 blockade in VSCC, measured by objective change in
tumour size (according to RECIST1.1)
- The activation, proliferation and migration of the CD4+CD39+PD-1+ intratumoral T-cell
population.
Phase:
Phase 2
Details
Lead Sponsor:
Leiden University Medical Center
Collaborators:
Erasmus Medical Center University Medical Center Groningen