Abstract 660P
Background
Immune checkpoint inhibitors are barely effective for the treatment of HPV-related squamous cell carcinoma refractory to chemotherapy. The generation of antigen-specific CD4 TH1 immune responses is an attractive strategy to promote anti-PD-1/L1 efficacy. UCPVax is a therapeutic cancer vaccine composed of two MHC-class II restricted promiscuous peptides derived from telomerase (hTert). We have previously demonstrated the safety and immunogenicity of UCPVax monotherapy (J Clin Oncol. 2023;41(2):373-384). Since HPV oncoproteins transactivate hTert, we hypothesized that UCPVax might enhance anti-PD-1/L1 efficacy in HPV-related squamous cell carcinoma.
Methods
HPV+ cancers, refractory to at least one line of systemic chemotherapy, were treated with atezolizumab every 3 weeks in combination with the UCPVax vaccine at 1 mg subcutaneously at days 1, 8, 15, 29, 36 and 43 (priming phase) followed by boost vaccinations: every 6/9 weeks. The primary end point was the objective response rate (ORR) at 4 months.
Results
44 patients (30 cervical/vulvar carcinoma, 12 anal carcinomas, 2 head and neck cancers). The median number of prior therapy lines was 3 (1-6). Mean age was 54 years (33-82). 25 patients had metastatic diseases and 19 a locally advanced disease resistant to radiotherapy and chemotherapy. Overall, 8 patients (6 cervical and 2 anal cancers) achieved an objective clinical response at 4 months. The 12-month PFS and OS rates were 24.2% and 60.5% respectively in the whole population. 33 patients had HPV-related ctDNA detectable at baseline. ctDNA burden decrease occurred in 22 patients (including 8 complete molecular remissions). Median PFS was 7.9 months when HPV ctDNA decreased compared to 2.3 months in the absence of ctDNA response. Five serious adverse reactions were reported (3 injection site reactions, 1 encephalitis, 1 peripheral neuropathy) and resolved without sequalae. Two patients discontinued treatment due to toxicity.
Conclusions
Atezolizumab and hTert-derived CD4 TH1 inducing vaccine induced durable clinical responses in advanced HPV+ squamous cell carcinoma and deserves further investigations.
Clinical trial identification
NCT03946358.
Editorial acknowledgement
Legal entity responsible for the study
University Hospital of Besançon.
Funding
Roche.
Disclosure
F. Ghiringhelli: Financial Interests, Personal, Invited Speaker: Eli Lilly, Sanofi, BMS, AstraZeneca, Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Merck Serono, Amgen, Sanofi. C. de la Fouchardiere: Financial Interests, Personal, Advisory Board: Amgen, Astellas, Bayer, BMS, Daiichi Sankyo, Incyte, Lilly, Merck, MSD, Roche, Servier; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Eisai, Ipsen, MSD, Pierre Fabre, Servier. B. You: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, GSK, Tesaro, Bayer, Roche Genentech, Novartis, Amgen, Merck Serono, Clovis Oncology, BMS, Seagen, Myriad, Menarini, Gilead, Eisai. E. Kalbacher: Financial Interests, Personal, Advisory Board: Seagen, AstraZeneca, GSK. F. Bazan: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Eisai, Menarini, Novartis. A. Vienot: Financial Interests, Personal, Invited Speaker: Servier, MSD. A. Tanang: Financial Interests, Institutional, Affiliate: Roche. S. Kim: Financial Interests, Personal, Invited Speaker: MSD, BMS; Financial Interests, Personal, Research Grant: Roche. O. Adotevi: Financial Interests, Personal, Research Grant: MSD, BMS, Roche; Financial Interests, Personal, Invited Speaker: MSD, BMS. C. Borg: Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Advisory Board: Bayer, Molecular Partner; Financial Interests, Personal, Invited Speaker: MSD, Pierre Fabre, Servier, AstraZeneca. All other authors have declared no conflicts of interest.
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