NCT03946358

Combination of UCPVax Vaccine and Atezolizumab for the Treatment of Human Papillomavirus Positive Cancers (VolATIL)

A Phase II Study Evaluating the Interest to Combine UCPVax a CD4 TH1-inducer Cancer Vaccine and Atezolizumab for the Treatment of Human PapillomaVirus Positive Cancers

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 47 (actual)
• Sponsor: Centre Hospitalier Universitaire de Besancon · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

70% all cases of cervical cancer, 95% of anal cancers and about 70% of oropharyngeal cancers are linked to Human Papillomavirus (HPV) infection. HPV oncogenic proteins are trans-activators of telomerase. Indeed, E6 oncoprotein transactivates the human telomerase (hTert). Our group has conducted a clinical trial (NCT02402842) in advanced squamous cell anal cancer (SCCA) and investigators have shown a correlation between the presence of anti-HPV immunity and anti-telomerase T helpher 1 (TH1) CD4 T cell responses, establishing telomerase as an appropriate antigen in HPV-related cancers. Tumor-reactive CD4+ T cells have been found to ensure efficient effector Cytotoxic T Lymphocytes (CTL) recruitment at the tumor site. Promoting tumor specific TH1 CD4 activation might be an attractive therapeutic option to enhance anti-PD-1/PD-L1 (Programmed cell Death-1/Programmed cell Death-Ligand1) efficacy. However, no option is currently available to expand tumor specific TH1 lymphocytes in most patients. Then, investigators have identified four novel MHC (Major Histocompatibility Complex) class II-restricted peptides derived from human telomerase reverse transcriptase (TERT) referred as "Universal Cancer Peptides" (UCP). UCPVax is a therapeutic cancer vaccine developed by our team and composed of two separate peptides called UCP2 and UCP4 derived from telomerase. This UCPVax vaccine is currently evaluated in a multicenter phase I/II study in Non Small Lung Cancer (NSCLC) (NCT2818426) and seems to show to be safe and immunogenic. PD-1/PD-L1 immune checkpoint is a relevant candidate target for immunotherapy in HPV+ cancers, based on the prominent role of PD-1 and its ligand PD-L1 in HPV-driven immune-evasion. There is a strong rational of using PD-1 therapy in HPV+ cancers, however anti-PD-1/PD-L1 treatment induces a limited number of long term responses in HPV disease. Combining anti-PD-1/PD-L1 therapy with an antitumor vaccine gains serious consideration in HPV+ cancers. Indeed, anti-cancer vaccines can induce tumor-specific T cells expansion and activation and therefore restore the cancer-immunity cycle in patients lacking pre-existing anti-tumor responses. So investigators propose to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer vaccine (UCPVax) with atezolizumab in patients with HPV+ cancers by evaluation of the objective response rate at 4 months according to iRecist criteria.

Conditions

• Squamous Cell Carcinoma of the Head and Neck
• Anal Canal Cancer
• Cervical Cancer

Interventions

Type	Name	Description
BIOLOGICAL	Blood sample collection	Four blood samples will be collected at: * baseline * 2 months from inclusion (+/- 1 week) * 4 months from inclusion (+/- 1 week) * the end of vaccination visit (+/- 1 week). A total of 8 EDTA (ethylenediaminetetraacetic acid) tubes of 6 ml will be collected at each time point to perform: PBMC collection: 6 EDTA tubes of 6 ml of peripheral blood mononuclear cell \[PBMC\] will be sent to the central laboratory (Biomonitoring Platform of Besançon, CHRU de Besançon located at Etablissement Français du Sang) at room temperature within 24 hours via an approved carrier for their processing, storage and immunomonitoring analysis. A sending sheet of the samples will be attached to each single sample. Plasma collection: One 6 ml EDTA tube should be frozen in each investigation center for plasma collection. Plasma for circulating tumoral DNA (ctDNA) collection: One 6 ml EDTA tube should be frozen in each investigation center for ctDNA collection.
PROCEDURE	Tumor biopsies	A tumor biopsy will be realized and centralized at baseline and at 2 months. Collection of tumor biopsies will be guided by ultrasound or CT scan
OTHER	CT scan	A CT scan will be planned * at baseline * at tumor evaluation visit (8 weeks) * every 8 weeks (+/- 1 week) * at end of treatment visit.
DRUG	Atezolizumab	Induction phase: Atezolizumab 1200 mg intravenous every 3 weeks since day 1 Boost phase: Atezolizumab 1200 mg intravenous every 3 weeks until disease progression or unacceptable toxicity until disease progression or unacceptable toxicity.
DRUG	UCPVax	Induction phase: UCPVax (combined with Montanide ISA51 as adjuvant) at 1 mg subcutaneously in two separate sites (one site per peptide) at day 1, 8, 15, 29, 36 and 43 (induction phase). Boost phase: UCPVax boosts vaccine every 6 weeks for the 2 first boosts (boost 1 and boost 2) and then every 9 weeks (boost 3 to boost 5).

Timeline

• Start date: 2020-02-18
• Primary completion: 2024-03-01
• Completion: 2024-11-01
• First posted: 2019-05-10
• Last updated: 2024-12-20

Locations

4 sites across 1 country: France