Intranasal WSK-IM05 Vaccine Plus Tislelizumab as Neoadjuvant Therapy for HPV+ OPSCC

Summary

This phase I, open-label, single-arm trial uses a "3+3" dose-escalation design to evaluate the safety, tolerability, and preliminary efffcacy of intranasal WSK-IM05 vaccine combined with tislelizumab as neoadjuvant therapy in patients with resectable HPV-positive oropharyngeal squamous cell carcinoma. Participants receive two cycles of WSK-IM05 (intranasal) and tislelizumab (200 mg IV) on day 1 of each 3-week cycle, followed by surgery. After surgery, patients receive standard of care (chemoradiotherapy or radiotherapy as indicated) plus 15 cycles of adjuvant tislelizumab. The main outcomes include dose-limiting toxicities and treatment-related adverse events.

Timeline

Start

2026-05-10

Primary completion

2027-05-10

Completion

2028-05-10

Publications

• Background Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011 Nov 10;29(32):4294-301. doi: 10.1200/JCO.2011.36.4596. Epub 2011 Oct 3.
• Background Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma. J Clin Oncol. 2015 Oct 10;33(29):3235-42. doi: 10.1200/JCO.2015.61.6995. Epub 2015 Sep 8.
• Background Senkomago V, Henley SJ, Thomas CC, Mix JM, Markowitz LE, Saraiya M. Human Papillomavirus-Attributable Cancers - United States, 2012-2016. MMWR Morb Mortal Wkly Rep. 2019 Aug 23;68(33):724-728. doi: 10.15585/mmwr.mm6833a3.
• Background Schache AG, Powell NG, Cuschieri KS, Robinson M, Leary S, Mehanna H, Rapozo D, Long A, Cubie H, Junor E, Monaghan H, Harrington KJ, Nutting CM, Schick U, Lau AS, Upile N, Sheard J, Brougham K, West CM, Oguejiofor K, Thomas S, Ness AR, Pring M, Thomas GJ, King EV, McCance DJ, James JA, Moran M, Sloan P, Shaw RJ, Evans M, Jones TM. HPV-Related Oropharynx Cancer in the United Kingdom: An Evolution in the Understanding of Disease Etiology. Cancer Res. 2016 Nov 15;76(22):6598-6606. doi: 10.1158/0008-5472.CAN-16-0633. Epub 2016 Aug 28.
• Background Craig SG, Anderson LA, Schache AG, Moran M, Graham L, Currie K, Rooney K, Robinson M, Upile NS, Brooker R, Mesri M, Bingham V, McQuaid S, Jones T, McCance DJ, Salto-Tellez M, McDade SS, James JA. Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach. Br J Cancer. 2019 Apr;120(8):827-833. doi: 10.1038/s41416-019-0414-9. Epub 2019 Mar 20.
• Background Lechner M, Liu J, Masterson L, Fenton TR. HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management. Nat Rev Clin Oncol. 2022 May;19(5):306-327. doi: 10.1038/s41571-022-00603-7. Epub 2022 Feb 1.
• Background Uppaluri R, Haddad RI, Tao Y, Le Tourneau C, Lee NY, Westra W, Chernock R, Tahara M, Harrington KJ, Klochikhin AL, Brana I, Vasconcelos Alves G, Hughes BGM, Oliva M, Pinto Figueiredo Lima I, Ueda T, Rutkowski T, Schroeder U, Mauz PS, Fuereder T, Laban S, Oridate N, Popovtzer A, Mach N, Korobko Y, Costa DA, Hooda-Nehra A, Rodriguez CP, Bell RB, Manschot C, Benjamin K, Gumuscu B, Adkins D; KEYNOTE-689 Investigators. Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer. N Engl J Med. 2025 Jul 3;393(1):37-50. doi: 10.1056/NEJMoa2415434. Epub 2025 Jun 18.
• Background Leidner R, Crittenden M, Young K, Xiao H, Wu Y, Couey MA, Patel AA, Cheng AC, Watters AL, Bifulco C, Morris G, Rushforth L, Nemeth S, Urba WJ, Gough M, Bell RB. Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma. J Immunother Cancer. 2021 May;9(5):e002485. doi: 10.1136/jitc-2021-002485.
• Background Massarelli E, William W, Johnson F, Kies M, Ferrarotto R, Guo M, Feng L, Lee JJ, Tran H, Kim YU, Haymaker C, Bernatchez C, Curran M, Zecchini Barrese T, Rodriguez Canales J, Wistuba I, Li L, Wang J, van der Burg SH, Melief CJ, Glisson B. Combining Immune Checkpoint Blockade and Tumor-Specific Vaccine for Patients With Incurable Human Papillomavirus 16-Related Cancer: A Phase 2 Clinical Trial. JAMA Oncol. 2019 Jan 1;5(1):67-73. doi: 10.1001/jamaoncol.2018.4051.
• Background Chung V, Kos FJ, Hardwick N, Yuan Y, Chao J, Li D, Waisman J, Li M, Zurcher K, Frankel P, Diamond DJ. Evaluation of safety and efficacy of p53MVA vaccine combined with pembrolizumab in patients with advanced solid cancers. Clin Transl Oncol. 2019 Mar;21(3):363-372. doi: 10.1007/s12094-018-1932-2. Epub 2018 Aug 9.

Drugs

Indications