Abstract 2536
Background
TG4001 is a vaccine targeting HPV E6 and E7. It has shown to provide histological clearance of cervical pre-cancerous lesions (Harper DM et al. 2019). We aimed to evaluate in the Ph Ib part the safety of TG4001 in combination with avelumab in HPV 16-positive cancers (NCT03260023).
Methods
Patients with HPV-16 positive cancers who had received ≤ 2 prior regimens for R/M disease were enrolled to either one of the two doses of the vaccine (5x106 and 5x107 pfu). TG4001 was administered SC weekly for 6 weeks, every 2 weeks up to M6, and every 12 weeks thereafter. Avelumab was given IV at 10mg/kg every 2 weeks. Tumor response was assessed by RECIST 1.1. For translational and immunological assessments, PBMC samples were collected longitudinally and tissue samples were collected at baseline and D43.
Results
Nine patients with oropharyngeal (5), anal (2), cervical (1) or vaginal (1) cancer, were enrolled in this trial, 3 patients on the low dose and 6 patients on the high dose of TG4001. No dose-limiting toxicity and no SAE have been observed. 3 patients had a confirmed partial response according to RECIST1.1. 3/5 evaluable patients for T-cell response by ELISPOT displayed detectable peripheric responses against E6 and/or E7 after treatment, and an overall trend to decreased circulating regulatory T cells (Treg). At the tissue level, 4/5 evaluable patients showed an increase of CD8 infiltration and/or a decrease in infiltrated Treg/CD8 ratio at day 43. The percentage of PD-L1+ cells doubled in all low or moderate expressors. The phenotypic findings were supported by increased expression of genes associated with both adaptive and innate immunity and with a shift from a “cold” tumor to a “hot” tumor gene signature.
Conclusions
The combination of TG4001 and avelumab is safe and provides anti-tumor activity in HPV-16+ cancer patients. The treatment induces immune changes in patients with poor baseline immune contexture. The combination is being evaluated in the ongoing Ph II part.
Clinical trial identification
NCT03260023.
Editorial acknowledgement
Legal entity responsible for the study
Transgene SA.
Funding
Transgene.
Disclosure
C. Le Tourneau: Advisory / Consultancy: MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Nanobiotix; Advisory / Consultancy: GSK. J. Delord: Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Research grant / Funding (institution): MSD; Advisory / Consultancy: EMD Serono; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): AstraZeneca. P. Cassier: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Research grant / Funding (institution): Blueprint Medicines; Honoraria (self), Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Plexxikon; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Sharp & Dohme; Research grant / Funding (institution): Taiho Pharmaceuticals; Research grant / Funding (institution): Toray Industries; Research grant / Funding (institution): Transgene; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Innate Pharma; Research grant / Funding (institution): Janssen. D. Loirat: Advisory / Consultancy: Roche; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD. A. Tavernaro: Full / Part-time employment: Transgene SA. B. Bastien: Full / Part-time employment, Employed by sponsor of the study: Transgene SA. K. Bendjama: Shareholder / Stockholder / Stock options, Full / Part-time employment: Transgene.
Resources from the same session
5877 - Efficacy of anti-PD(L)1 treatment in patients with metastatic urothelial cancer based on mRNA- and protein- based PD-L1 determination: Results from the multicentric, retrospective FOsMIC trial
Presenter: Jonas Jarczyk
Session: Poster Display session 3
Resources:
Abstract
5204 - A differential bladder microbiota composition is associated with tumor grade in bladder cancer.
Presenter: Monica Parra-Grande
Session: Poster Display session 3
Resources:
Abstract
4904 - Molecular characterization of metastatic urothelial carcinoma (mUC) in prior or current smokers (PCS) vs non-smokers (NS)
Presenter: Victor Sacristan Santos
Session: Poster Display session 3
Resources:
Abstract
5370 - Evaluation of different diagnostic methods for identification of FGFR alteration in advanced urothelial carcinomas: Proficiency Results based on multiple RNA extraction kits and mutation detection methods
Presenter: Veronika Weyerer
Session: Poster Display session 3
Resources:
Abstract
2579 - Title: Genomic characterization of non-schistosomiasis-related squamous cell carcinoma (NSR-SCC) of the urinary bladder: a retrospective study of potential prognostic and predictive biomarkers
Presenter: Esmail Al-ezzi
Session: Poster Display session 3
Resources:
Abstract
2203 - TiNivo: Tivozanib combined with nivolumab results in prolonged progression free survival in patients with metastatic renal cell carcinoma (mRCC). Final Results.
Presenter: Philippe Barthelemy
Session: Poster Display session 3
Resources:
Abstract
4712 - First-Line Pembrolizumab (pembro) Monotherapy for Advanced Non‒Clear Cell Renal Cell Carcinoma (nccRCC): Updated Follow-Up for KEYNOTE-427 Cohort B
Presenter: Cristina Suárez
Session: Poster Display session 3
Resources:
Abstract
2091 - First-Line Pembrolizumab (pembro) Monotherapy in Advanced Clear Cell Renal Cell Carcinoma (ccRCC): Updated Follow-Up For KEYNOTE-427 Cohort A
Presenter: James Larkin
Session: Poster Display session 3
Resources:
Abstract
2368 - Association Between Depth of Response and Overall Survival: Exploratory Analysis in Patients With Previously Untreated Advanced Renal Cell Carcinoma (aRCC) in CheckMate 214
Presenter: Viktor Grünwald
Session: Poster Display session 3
Resources:
Abstract
6008 - Quality of life in previously untreated patients with advanced renal cell carcinoma (aRCC) in CheckMate 214: updated results
Presenter: David Cella
Session: Poster Display session 3
Resources:
Abstract