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.

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 .