2536 - Phase Ib/II trial of TG4001 (Tipapkinogene sovacivec), a therapeutic HPV-vaccine, and Avelumab in patients with recurrent/metastatic (R/M) HPV-16+ cancers

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.