157P - Preliminary results of a multicentric randomized phase I/IIa trial of an immunotherapy targeting dendritic cells (DC), CD40HVac, in patients with HPV16-positive oropharyngeal carcinoma (OPC)

Background

Up to 70% of OPC are HPV-mediated with most caused by HPV16. Oncoproteins E6/E7 are constitutively expressed in HPV-infected malignant cells and ideal immunotherapeutic target antigens (Ag). We tested a new Ag delivery using CD40HVac, a sub-unit vaccine composed of a humanized IgG4 monoclonal antibody fused to HPV16 E6/E7 proteins, targeting CD40 receptor of DCs.

Methods

HPV.DCVax phase I/IIa dose-escalation trial (NCT06007092), planned to recruit OPC HPV16+ patients (pts), in complete remission after curative treatment. Twelve pts were included per dose group (1 (completed), or 3 mg (ongoing) CD40HVac subcutaneously-adjuvanted with Hiltonol®1mg), and randomized 5:1 to receive vaccine or placebo at Week (W) 0, 4 and 24 starting 16 – 22 W after end of curative treatment. Dose limiting toxicity (DLT) was evaluated from W0-W6 and immunogenicity at W6, 26 and 48. We report blinded safety and immunogenicity results at W6 from the 1^st cohort. Blood E6/E7 specific T-cells responses were evaluated after in vitro expansion (8d) and ex vivo stimulation (24h) with E6/E7 peptide pools and assessed by cytokine expression or activation induced markers (AIM), respectively.

Results

In the 1^st cohort, 12 pts (median 56 years, 67% male) were randomized in median 20W after the end of curative treatment. All patients had a lymphopenia, two of grade 3. During the DLT period (W0-W6), no AE of grade 3, 4 or 5 was observed. All AEs reasonably related to injection were grade 1 with a short duration, but one grade 2 neutropenia. At W6, compared to W0, 9/11 pts had a 24-fold increase in E6/E7-specific CD4+ T cells, and 5/11 had a 7-fold increase in CD8+ T cells, producing IL-2, IFN-γ, and/or TNF. Responses against E6 and E7 were induced. Specific CD8+T cells exhibited IFN-g, TNF, Granzyme B and CD107a, markers of cytotoxicity. AIM assay confirmed the elicitation of HPV-specific CD4+ and CD8+ T cells.

Conclusions

Adjuvanted CD40HVac immunotherapy is well tolerated in OPC HPV16-positive pts and induced, after two boosts at the lowest dose, specific and functional T-cell responses including CD8+ T cells exhibiting markers of cytotoxicity. W26 immunogenicity results will be presented.

Clinical trial identification

NCT06007092 EuCT N°: 2022-502930-25-00.

Legal entity responsible for the study

Gustave Roussy.

Funding

EnnoDC.

Disclosure

C. Even: Financial Interests, Personal, Advisory Board: BMS, MSD, Innate Pharma, Merck Serono; Financial Interests, Institutional, Advisory Board: F Star Therapeutics, Novartis, Elevar, BICARA, PDS Biotechnology, GSK, MERUS; Financial Interests, Institutional, Local PI: BMS, AstraZeneca, ISA Pharmaceutics, MSD, Debiopharm, Ayala, Gilead, GSK, Beigene, Takeda, Genmab, Seagen, Nykode; Financial Interests, Institutional, Coordinating Pi: BMS, Novartis, Sanofi. C. Le Tourneau: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck Serono, Nanobiotix, Roche, Rakuten, Seattle Genetics, GSK, Celgene, ALX Oncology, Exscientia. M. Codou: Financial Interests, Personal, Full or part-time Employment: EnnoDC. M. Centlivre: Financial Interests, Personal, Other: EnnoDC. Y. Levy: Financial Interests, Personal, Other: EnnoDC. All other authors have declared no conflicts of interest.