Slide 1: Randomized phase I trial of adjuvant personalized cancer vaccine TG4050 in resected, locally advanced HNSCC
Randomized phase I trial of adjuvant personalized cancer vaccine TG4050 in resected, locally advanced HNSCC patients (TG4050.02) C. Le Tourneau1, JP. Delord2, O. Lantz3, E. Dochy4, M. Ceppi4, C. Spring- Giusti4, K. Bidet Huang4, B. Bastien4, A. Tavernaro4, G. Lacoste4, P. Brattas5, A. Devanadera6, H
Slide 2: Key Takeaway Points
2 Key Takeaway Points 1 2 3 Adjuvant TG4050 TG4050 improves TG4050 induces personalized DFS with no neoantigen-specific vaccination is recurrences in the CD8 T cell feasible and safe in vaccinated arm after responses that locally advanced a median follow-up persist after the end HPV- resectable of 3
Slide 3: Background
3 Background • Standard of care for locally advanced HNSCC: - Unresectable disease or organ-sparing: radiotherapy +/- chemotherapy - Resectable disease: surgery followed by radiotherapy +/- chemotherapy • Immunotherapy targeting PD1 is becoming standard of care in resectable disease: - Neoadjuvant a
Slide 4: TG4050 personalized cancer vaccine
4 TG4050 • Viral-based personalized cancer vaccine using Modified Vaccinia Virus Ankara • Specifically manufactured for a given patient based on the identification of specific somatic mutations using tumor sequencing • Contains up to 30 MHC class I and II predicted patient-specific neoantigen epitop
Slide 5: Study design (NCT04183166)
5 Study design (NCT04183166) Key objectives: • Primary: Safety • Secondary: Feasibility Selection criteria #1: Selection criteria #2: DFS • Resectable HNSCC • Pathological stage III • Exploratory: Neoantigen specific from oral cavity, or IV response oropharynx, larynx, • Adjuvant therapy hypopharynx
Slide 6: Flow chart
6 Flow chart Arm A: N=17 • Adjuvant TG4050 - 17 patients evaluable for demographic and safety • TG4050 could be - 16 patients evaluable for given at DFS recurrence 80 Patients 33 Eligible R 1 patient non-evaluable for DFS* Consented Patients 1:1 47 Excluded Patients Arm B: N=16 • No adjuvant 15 Earl
Slide 7: Populations definition for statistical considerations
7 Populations definition for statistical considerations Population Definition per protocol Primary dataset Total number of patients (A/B) Full analysis All randomized patients Demographic and N=33 (17/16) set (FAS) baseline characteristics Safety All randomized patients who received Safety analysis
Slide 8: Patient characteristics
8 Patient characteristics Arm A (N=17) Arm B (N=16) Male / Female, n (%) 11 (65%) / 6 (35%) 13 (81%) / 3 (19%) Age (years), median (range) 61 (26 – 79) 57 (47 – 74) ECOG PS 0 / 1, n (%) 12 (71%) / 5 (29%) 9 (56%) / 7 (44%) Primary tumor location Oral cavity 14 (82%) 10 (63%) Oropharynx 2 (12%) 2 (13
Slide 9: Pathological risk factors
9 Pathological risk factors Arm A (N=17) Arm B (N=16) Extracapsular effraction, n (%) 5 (29%) 8 (50%) Invaded margins, n (%) 4 (24%) 3 (19%) Perineural infiltration, n (%) 13 (77%) 7 (44%) 4+ invaded lymph nodes, n (%) 2 (12%) 3 (19%) No. of risk factors, n (%) 0 3 (18%) 2 (13%) 1 5 (29%) 9 (56%) 2+
Slide 10: Safety
10 Safety Adjuvant TG4050 TG4050 at recurrence (N=17) (N=3) Patients with at least one AE related to TG4050, n (%) 16 (94%) 2 (67%) Dose-limiting toxicity 0 0 SAE 0 0 Grade 3-5 AEs 0 0 Grade 1/2 AEs related to TG4050 Injection site reaction 16 (94%) 1 (33%) Rash 2 (12%) 0 Fatigue 2 (12%) 0 Influenza
Slide 11: Efficacy
11 Efficacy 2-year DFS 100% Median FU of 30 months 81% PRESENTED BY: Christophe Le Tourneau, MD, PhD
Slide 12: Immune response
12 Immune response • Neoantigen-specific CD8 T cell responses to multiple vaccine epitopes in the same patient with no evidence of antigen immunodominance • Persistence of CD8 T cell responses over 1 year after the end of the treatment PRESENTED BY: Christophe Le Tourneau, MD, PhD
Slide 13: Conclusions
13 Conclusions Adjuvant personalized vaccination with TG4050 is feasible and safe in resectable HPV- locally advanced HNSCC patients, and induces long-lasting immune responses to vaccine neoantigens Adjuvant personalized vaccination with TG4050 improves DFS with no recurrences in the vaccinated arm,
Slide 14: Acknowledgments
14 Acknowledgments The authors wish to thank all patients, families, caregivers and all technical staff involved in the trial The study was industry co-funded by NEC CORPORATION and TRANSGENE Correspondence: Christophe.LeTourneau@curie.fr PRESENTED BY: Christophe Le Tourneau, MD, PhD