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

NCT07565740 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 2026-891
• Study Type: interventional
• Target: 9
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

HPV-positive Oropharyngeal Squamous Cell Carcinoma

Keywords

HPV-positive oropharyngeal squamous cell carcinoma; Neoadjuvant therapy; PD-1 inhibitor; Pathological response

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Major Pathological Response (MPR)

  At time of surgery (approx. Week 6-10)

• Pathological Complete Response (pCR)

  At time of surgery (approx. Week 6-10)

• Objective Response Rate (ORR)

  After 2 cycles of neoadjuvant therapy (prior to surgery, approx. Week 5-9)

• Event-Free Survival (EFS)

  From first dose up to approximately 3 years

Other Outcomes (3)

• Quantitative HPV Viral Load

  Baseline, after 2 cycles of neoadjuvant therapy, and after surgery/radiotherapy

• Vaccine-Induced Systemic and Local Immune Responses

  Baseline and after neoadjuvant therapy

• Biomarkers of Efffcacy

  Baseline (tumor tissue) and at surgery (post-treatment tissue)

Study Arms (3)

WSK-IM05 (4×10^10 vp) + Tislelizumab

EXPERIMENTAL

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); Biological: WSK-IM05 (1.6x10^11 vp)

Arm 2: WSK-IM05 (8×10^10 vp) + Tislelizumab

EXPERIMENTAL

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 (8×10^10 vp); Biological: WSK-IM05 (1.6x10^11 vp)

Arm 3: WSK-IM05(1.6×10^11 vp) + Tislelizumab

EXPERIMENTAL

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); Drug: Tislelizumab

Interventions

WSK-IM05 (4×10^10 vp) BIOLOGICAL

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.

WSK-IM05 (4×10^10 vp) + Tislelizumab

WSK-IM05 (8×10^10 vp) BIOLOGICAL

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.

Arm 2: WSK-IM05 (8×10^10 vp) + Tislelizumab

WSK-IM05 (1.6x10^11 vp) BIOLOGICAL

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.

Arm 2: WSK-IM05 (8×10^10 vp) + Tislelizumab; Arm 3: WSK-IM05(1.6×10^11 vp) + Tislelizumab; WSK-IM05 (4×10^10 vp) + Tislelizumab

Tislelizumab DRUG

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).

Arm 3: WSK-IM05(1.6×10^11 vp) + Tislelizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.

Sponsors & Collaborators

• West China Hospital: lead

Related Publications (10)

• 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.

  PMID: 21969503 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.

  PMID: 26351338 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.

  PMID: 31437140 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.

  PMID: 27569214 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.

  PMID: 30890775 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.

  PMID: 35105976 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.

  PMID: 40532178 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.

  PMID: 33963014 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.

  PMID: 30267032 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.

  PMID: 30094792 BACKGROUND

MeSH Terms

Interventions

tislelizumab

Central Study Contacts

Xingchen Peng

CONTACT

18980606753; pxx2014@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 27, 2026
• First Posted: May 4, 2026
• Study Start (Estimated): May 10, 2026
• Primary Completion (Estimated): May 10, 2027
• Study Completion (Estimated): May 10, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share