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

A Prospective, Single-Arm Clinical Study of Intranasal Recombinant Adenovirus Vaccine WSK-IM05 Combined With Tislelizumab as Neoadjuvant Therapy for HPV-Positive Oropharyngeal Squamous Cell Carcinoma

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.

Study Overview

• Status: Recruiting
• Conditions: HPV-positive Oropharyngeal Squamous Cell Carcinoma
• Intervention / Treatment: Biological: WSK-IM05 (4×10^10 vp); Biological: WSK-IM05 (1.6x10^11 vp); Biological: WSK-IM05 (8×10^10 vp); Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xingchen Peng; Phone Number: 18980606753; Email: pxx2014@163.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Recruiting
      • West China Hospital, Sichuan University
      • Contact: Sichuan University West China Hospital; Phone Number: +8602885421141; Email: pxx2014@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years, male or female.2. Histologically confirmed oropharyngeal squamous cell carcinoma meeting all of the following criteria: Newly diagnosed, HPV-positive, without distant metastases; Confirmed p16 positive by immunohistochemistry (defined as ≥70% moderate to strong nuclear and cytoplasmic staining of tumor cells)；Assessed by head and neck surgery as resectable; Willing to undergo surgical treatment.3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.4. Adequate organ and bone marrow function, defined as:Hematology: neutrophil count (NEUT) ≥ 1.5×10⁹/L; platelet count (PLT) ≥ 80×10⁹/L; hemoglobin ≥ 8 g/dL; Liver function: AST, ALT, ALP ≤ 2.5×upper limit of normal (ULN); total bilirubin (TBIL) ≤ 1.5×ULN; Albumin ≥ 2.8 g/dL.Renal function: serum creatinine (Cr) ≤ 1.5×ULN or creatinine clearance (CCr) > 60 mL/min; Coagulation: international normalized ratio (INR) ≤ 1.5; activated partial thromboplastin time (APTT) ≤ 1.5×ULN; Adenovirus type 5(Ad5) neutralizing antibody titer ≤ 1:200.5. Willing to voluntarily sign the informed consent form and able to comply with protocol-required visits and procedures.

Exclusion Criteria:

1. History of other malignancies (except for adequately treated and with no recurrence within 5 years:basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer,cervical carcinoma in situ, intramucosal gastrointestinal carcinoma, or other malignancies deemed eligible by the investigator).2. Any active autoimmune disease or history of autoimmune disease,including but not limited to immune-related neurological disorders, multiple sclerosis, autoimmune(demyelinating) neuropathy, Guillain-Barré syndrome, myasthenia gravis, systemic lupus erythematosus(SLE), connective tissue disease, scleroderma, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), autoimmune hepatitis, toxic epidermal necrolysis (TEN), or Stevens-Johnson syndrome (excluding type I diabetes mellitus managed with stable insulin doses).3. History of allergic disease, severe drug allergy, or known allergy to any component of large molecule protein preparations,PD-1 monoclonal antibody injections, or the intranasal recombinant adenovirus vaccine (note: severe allergy is defined as requiring hospitalization).4. Prior receipt of any of the following treatments:a. Prior use of PD-1 antibody, PD-L1 antibody, PD-L2 antibody, CTLA-4 antibody, EGFR antibody, or EGFR-TKI.b. Prior receipt of an antitumor vaccine.c. Use of any active vaccine against infectious diseases (e.g.,inffuenza vaccine, varicella vaccine) within 4 weeks before first dose or planned during the study period.d. Major surgery or severe trauma within 4 weeks before first dose.e. Prior antitumor toxicity not recovered to ≤ CTCAE v5.0 grade 1 (excluding alopecia or sequelae of prior platinum-related neuropathy) or to the levels specified in inclusion/exclusion criteria.5. Presence of severe medical conditions, such as: Cardiac dysfunction grade II or higher (NYHA criteria), ischemic heart disease (e.g., myocardial infarction or angina), clinically significant supraventricular or ventricular arrhythmias; Poorly controlled diabetes (fasting blood glucose ≥ 10 mmol/L); Poorly controlled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg); Echocardiography showing ejection fraction < 50%; QTc interval: > 450 msec in males, > 470 msec in females; Any ECG abnormality that, in the investigator's opinion, poses additional risk for the study drug.6. History of interstitial lung disease, non-infectious pneumonitis, or high suspicion of interstitial lung disease; or conditions that might interfere with detection or management of suspected drug-related pulmonary toxicity. Patients with a prior history of drug-induced or radiation-induced non-infectious pneumonitis who are asymptomatic may be enrolled. Active tuberculosis or past tuberculosis that remains uncontrolled after treatment.7. Patients with hyperthyroidism or organic thyroid disease. Hypothyroidism managed with a stable dose of thyroid replacement hormone may be enrolled (as conffrmed by the investigator and/or endocrinologist).8. Active infection, or unexplained fever within 48 hours before first dose, or use of systemic antibiotics within 1 week before signing informed consent.9. Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL) or active hepatitis C (positive HCV antibody with HCV RNA above the lower limit of detection), or known positive HIV test or known acquired immunodeffciency syndrome (AIDS).10. Clear history of neurological or psychiatric disorders, such as epilepsy or dementia.11. Clear history of drug abuse or alcohol abuse within 3 months.12. Pregnant or breast feeding women; participants (and their partners) who plan to conceive within 3 months after the study period, have unprotected sexual intercourse, or are unwilling to use adequate contraceptive measures (e.g., condom,intrauterine device, or partner sterilization).13. Receipt of any investigational drug within 4 weeks before first dose, or concurrent enrollment in another clinical study, unless it is an observational (non-interventional) study or the follow-up phase of an interventional study.14. Any other condition that,in the investigator's judgment, might interfere with the study, including inability to complete study treatment and follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WSK-IM05 (4×10^10 vp) + Tislelizumab; Participants receive two cycles (each cycle = 3 weeks) of neoadjuvant treatment. On day 1 of each cycle: intranasal WSK-IM05 vaccine at a dose of 4×10^10 vp and tislelizumab 200 mg intravenously. After two cycles, patients undergo radical surgery followed by standard postoperative therapy plus 15 cycles of adjuvant tislelizumab (200 mg every 3 weeks). Dose-limiting toxicity (DLT) is assessed during the first 21 days after the first dose.	Biological: WSK-IM05 (4×10^10 vp); Intranasal recombinant adenovirus vaccine WSK-IM05 at a dose of 4×10^10 vp administered via nasal spray on day 1 of each 3-week cycle for 2 cycles.; Biological: WSK-IM05 (1.6x10^11 vp); Intranasal recombinant adenovirus vaccine WSK-IM05 at a dose of 1.6x10^11 vp administered via nasal spray on day 1 of each 3-week cycle for 2 cycles.
Experimental: Arm 2: WSK-IM05 (8×10^10 vp) + Tislelizumab; Participants receive two cycles (each cycle = 3 weeks) of neoadjuvant treatment. On day 1 of each cycle: intranasal WSK-IM05 vaccine at a dose of 8×10^10 vp and tislelizumab 200 mg intravenously. After two cycles, patients undergo radical surgery followed by standard postoperative therapy plus 15 cycles of adjuvant tislelizumab (200 mg every 3 weeks). Dose-limiting toxicity (DLT) is assessed during the first 21 days after the first dose.	Biological: WSK-IM05 (1.6x10^11 vp); Intranasal recombinant adenovirus vaccine WSK-IM05 at a dose of 1.6x10^11 vp administered via nasal spray on day 1 of each 3-week cycle for 2 cycles.; Biological: WSK-IM05 (8×10^10 vp); Intranasal recombinant adenovirus vaccine WSK-IM05 at a dose of 8×10^10 vp administered via nasal spray on day 1 of each 3-week cycle for 2 cycles.
Experimental: Arm 3: WSK-IM05(1.6×10^11 vp) + Tislelizumab; Participants receive two cycles (each cycle = 3 weeks) of neoadjuvant treatment. On day 1 of each cycle: intranasal WSK-IM05 vaccine at a dose of 1.6×10^11 vp and tislelizumab 200 mg intravenously. After two cycles, patients undergo radical surgery followed by standard postoperative therapy plus 15 cycles of adjuvant tislelizumab (200 mg every 3 weeks). Dose-limiting toxicity (DLT) is assessed during the first 21 days after the first dose.	Biological: WSK-IM05 (1.6x10^11 vp); Intranasal recombinant adenovirus vaccine WSK-IM05 at a dose of 1.6x10^11 vp administered via nasal spray on day 1 of each 3-week cycle for 2 cycles.; Drug: Tislelizumab; Tislelizumab at a dose of 200 mg administered intravenously on day 1 of each 3-week cycle for 2 cycles (neoadjuvant phase), followed by 200 mg intravenously every 3 weeks for 15 cycles (adjuvant phase after surgery).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose-Limiting Toxicities (DLTs)	Proportion of participants experiencing DLTs within the DLT observation period (first 21 days after the first dose), as defined per protocol.	First 21 days after first dose of WSK-IM05
Incidence and Severity of Treatment-Related Adverse Events (TRAEs)	Type, incidence, severity (grade 1-5 according to CTCAE v5.0), and causality assessment of all treatment-related adverse events.	From first dose through 30 days after last dose of WSK-IM05
Incidence of Serious Adverse Events (SAEs)	Including immune-related adverse events (irAEs), injection/administration site reactions, allergic reactions, etc.	From first dose through 30 days after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response (MPR)	Proportion of participants who undergo surgery with residual viable tumor ≤10% (%RVT ≤10%) in the tumor bed according to irPRC criteria, regardless of lymph node status.	At time of surgery (approx. Week 6-10)
Pathological Complete Response (pCR)	Proportion of participants who undergo surgery with no residual viable tumor cells (%RVT = 0) in the tumor bed and resected lymph nodes according to irPRC criteria.	At time of surgery (approx. Week 6-10)
Objective Response Rate (ORR)	Proportion of participants achieving complete response (CR) or partial response (PR) according to RECIST 1.1 criteria.	After 2 cycles of neoadjuvant therapy (prior to surgery, approx. Week 5-9)
Event-Free Survival (EFS)	Time from first dose to first occurrence of any of the following: disease progression during neoadjuvant therapy leading tolerability to undergo radical surgery; local, regional, or distant tumor recurrence after surgery; or death from any cause.	From first dose up to approximately 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative HPV Viral Load	Quantitative HPV titer in blood and saliva samples assessed before treatment and after neoadjuvant therapy, as a marker of treatment response.	Baseline, after 2 cycles of neoadjuvant therapy, and after surgery/radiotherapy
Vaccine-Induced Systemic and Local Immune Responses	Assessment of HPV16 E6/E7 Tetramer+ CD8+ T cells, TNF-α+/IFN-γ+ CD8+ T cells in peripheral blood, and anti-HPV16 E6/E7 antibodies.	Baseline and after neoadjuvant therapy
Biomarkers of Efffcacy	Correlation of tumor PD-L1 expression, tumor mutation burden (TMB), and changes in the tumor immune microenvironment with clinical efffcacy.	Baseline (tumor tissue) and at surgery (post-treatment tissue)

Collaborators and Investigators

• Sponsor: West China Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): May 10, 2026
• Primary Completion (Estimated): May 10, 2027
• Study Completion (Estimated): May 10, 2028

Study Registration Dates

• First Submitted: April 27, 2026
• First Submitted That Met QC Criteria: April 27, 2026
• First Posted (Actual): May 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Neoadjuvant therapy; PD-1 inhibitor; Pathological response; HPV-positive oropharyngeal squamous cell carcinoma
• Additional Relevant MeSH Terms: tislelizumab
• Other Study ID Numbers: 2026-891

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No