TheraVectys has announced the enrollment of the first patient in its Phase I/IIa clinical trial evaluating Lenti-HPV-07, a novel onco-therapeutic vaccine designed to combat cancers induced by the human papillomavirus (HPV). The trial, conducted across multiple cancer centers in the United States, marks a significant step forward in the development of targeted immunotherapies for HPV-related malignancies.
The open-label, dose-escalation trial aims to assess the safety, immunogenicity, and preliminary efficacy of Lenti-HPV-07 in 72 patients with oropharyngeal or cervical cancers caused by HPV-16 or HPV-18. Patients will be clinically and immunologically monitored for one year. The trial includes two groups: Group A, consisting of patients with recurrent or metastatic cancers who have not responded to prior treatments, will receive two intramuscular injections of Lenti-HPV-07 one month apart. Group B, composed of newly diagnosed patients with locally advanced cancers, will receive a single intramuscular injection.
Lenti-HPV-07: A Novel Lentiviral Vector Vaccine
Lenti-HPV-07 is based on a lentiviral vector technology platform developed by the Pasteur-TheraVectys Joint Laboratory. Preclinical studies published in EMBO Molecular Medicine and NPJ Vaccines have demonstrated promising results, including complete elimination of HPV-induced tumors, long-lasting immune memory, remodeling of the tumor microenvironment, and elimination of metastases following a single intramuscular injection. The vaccine targets the E6 and E7 antigens of HPV16 and HPV18, inducing a strong cellular immune response.
Trial Design and Objectives
The Phase I/IIa trial consists of a dose escalation and a dose expansion phase. The dose escalation portion will enroll participants successively to receive increasing doses of Lenti-HPV-07. Safety will be carefully monitored after each dose. Once safety results are satisfactory and 18 participants in each arm (A and B) have received treatment, a dose-expansion portion will open to treat an additional 18 patients at the Optimal Biological Dose in each arm.
Professor Christian Bréchot, Medical Director of TheraVectys, emphasized the importance of this milestone, stating, "The inclusion of the first patient in the Phase I/IIa trial represents a key milestone for TheraVectys...The careful selection of adequate partners and the development of a cooperative relationship have been key in successfully building the project."
Synergistic Potential with Anti-PD1 Therapies
Notably, patients in Group B, who are newly diagnosed and treatment-naïve, will receive standard care, including anti-PD1 treatments, one month after Lenti-HPV-07 administration. Preclinical data suggest that Lenti-HPV-07 acts synergistically with anti-PD1 antibodies, potentially increasing the efficacy of immunotherapy. TheraVectys has shown in animal models that the Lenti-HPV-07 vaccine acts synergistically with treatments such as anti-PD1, increasing the efficacy of anti-PD1 immunotherapy alone by a factor of 4.
Addressing Unmet Needs in HPV-Related Cancers
HPV is responsible for almost all cervical cancers, as well as a significant proportion of oropharyngeal and anogenital cancers. While preventive HPV vaccines are effective in preventing infection, they have no impact on chronic infections or established tumors. Lenti-HPV-07 represents a potential breakthrough in the treatment of these established HPV-induced cancers.
Pierre Charneau, head of the Pasteur-TheraVectys Joint Laboratory and founder of TheraVectys, stated, "With the launch of this study, we are proud to bring our product to a new phase of its development. We expect the preliminary results on safety and immunogenicity a couple of months after all patients in one group will have received their last injection."
