Randomized phase II trial evaluating the combination of TG4001, an HPV16 therapeutic vaccine, and avelumab (ave) in patients (pts) with immunotherapy-naïve recurrent and/or metastatic (R/M) HPV16-positive cervical or anogenital cancer.
Year: 2025
Type: conference-abstract
Abstract: 2638 Background: Human papillomavirus (HPV) is a small DNA virus associated with cervical, anogenital (AG) cancers and squamous cell carcinoma of the head and neck. TG4001 is a therapeutic vaccine based on modified vaccinia virus Ankara with insertion of modified non-oncogenic HPV-16 E6 and E7 antigens and interleukin-2 as adjuvant. The phase I trial of TG4001 combined with ave showed a favorable safety profile (Borcoman E. et al, 2023). Methods: Pts with R/M cervical and anogenital cancer and who were checkpoint inhibitors naïve were randomized independent of PD-L1 expression between ave plus TG4001 or ave alone. Pts were required to have no more than one prior line of therapy for R/M disease and no liver involvement. Primary endpoint was PFS. Subgroup analysis (cervical, anal, other genital cancer) was preplanned in the protocol. Results: 90 pts were randomized between June 2021 and April 2024. 49 (54%), 27 (30%) and 14 (16%) pts had cervical, anal, and other genital cancers, respectively. Patients’ demographics were well balanced between the 2 arms. Median PFS (mPFS) was 3.0 and 2.8 months (mo) in the experimental and control arm, respectively (HR=0.87 [90%CI: 0.59-1.29], p=0.28). In the cervical cancer subgroup, mPFS was 4.3 and 2.1 mo in the experimental and control arm, respectively (HR=0.58 [90%CI: 0.33-1.01], p=0.053). Overall Response Rate (ORR) in the whole population was 15.2% (7/46pts) in the experimental arm and 13.6% (6/44pts) in the control arm. In the cervical cancer subgroup ORR was 20% (5/25pts) in the experimental arm and 8.3% (2/24pts) in the control arm. There were no new safety signals. Three pts (6.5%) in the experimental arm and 2 pts (4.5%) in the control arm presented grade 3 or 4 treatment-related AEs. Translational analysis including immunogenicity results will be presented. Conclusions: TG4001 combined with ave did not improve PFS over ave alone in the whole patient population. Preplanned subgroup analysis in cervical cancer showed a positive efficacy signal in the combined arm. Avelumab was provided by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). Clinical trial information: NCT03260023 .
Source: Journal of Clinical Oncology
Authors: Christophe Le Tourneau, Frederic Rolland, Olivier Capitain, Philippe Alexandre Cassier, Jean David Fumet, Sebastien Salas, Amaury Daste, Luis Manso, Maria-Jose Bermejo-Perez, Antonio Casado, Laura Mansi, Patricia Pautier, Olivier Lantz, Emmanuelle Dochy, Clémentine Spring-Giusti, Katell Bidet Huang, Hakim Makhloufi, Céline Halluard, Annette Tavernaro, Jean-Pierre Delord
Institutions: Université Paris-Saclay, Institut Curie, Institut de Cancérologie de l'Ouest, Centre Léon Bérard, Centre Georges François Leclerc, Hôpital de la Timone, Université de Bordeaux, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Hospital Universitario 12 De Octubre, Hospital Clínico Universitario Virgen de la Victoria, Hospital Clínico San Carlos, Centre Hospitalier Universitaire de Besançon, Institut Gustave Roussy, Transgene (France), Institut universitaire du cancer de Toulouse Oncopole
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410810688