Intratumoral Delivery of Viral Replicon (saRNA) Particles Expressing IL-12 in Head and Neck Cancer

Study of Intratumoral Injections of VLPONC-01 in Head and Neck Cancer

The goal of this clinical trial is to assess the safety and tolerability of a virus replicon particle (VRP) encapsulated saRNA encoding IL-12 when injected into in head and neck cancer patients. The main questions being addressed are:

The safety and tolerability of intratumoral (IT) injections of VRP-encapsulated saRNA encoding IL-12 (VLPONC-01)

The tumor response to IT injections of VLPONC-01

The tumor response due to the combination of IT injections of VLPONC-01 and system IV administration of neoadjuvant pembrolizumab (anti-PD-1) treatment

Researchers will compare neoadjuvant pembrolizumab alone to the combination therapy to see if the combination enhances tumor responses.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer; Squamous Cell Carcinoma of the Head and Neck; Solid Tumors; Head and Neck Squamous Cell Cancer; Head Neck Cancer; Oral Cavity Carcinoma; HNSCC; Oral Cavity; Squamous Cell Carcinoma, Head And Neck; Head and Neck Cancers- Squamous Cell; Squamous Cell Head and Neck Carcinoma; SCCHN; SCC - Squamous Cell Carcinoma
• Intervention / Treatment: Biological: VRP-encapsulated saRNA encoding IL-12 (1 x 10^9 viral particles per injection); Drug: Pembrolizumab (KEYTRUDA®); Biological: VRP-encapsulated saRNA encoding IL-12 (3 x 10^8 viral particles per injection)

Detailed Description

The study is an Open label, Phase I study to determine the safety of IT injected VLPONC-01 as a therapeutic agent in subjects with non-resectable and resectable Head and Neck Cancer Squamous Cell Carcinomas (HCSCC), and secondarily to assess pathologic response and radiological response (assessed by RECIST 1.1 criteria) in the primary tumor and regional lymph nodes. Researchers also will explore tumor microenvironment changes in cytokine levels and cellular responses.

There will be three distinct cohorts enrolling sequentially:

Cohort A: Researchers will enroll unresectable or recurrent/metastatic head and neck cancer with at least 1 injectable tumor not scheduled for tumor resection surgery who will receive four doses of VLPONC-01.

Cohort C: Researchers will enroll HCSCC patients scheduled for tumor resection surgery who will receive four doses of VLPONC-1 and two doses of neoadjuvant pembrolizumab or only two doses of neoadjuvant pembrolizumab prior to tumor resection surgery.

• Study Type: Interventional
• Enrollment (Estimated): 41
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Research Coordinator; Phone Number: 650-725-9333; Email: tpark22@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 34305
      • Recruiting
      • Stanford University
      • Contact: Clinical Research Coordinator; Phone Number: 650-725-9333; Email: tpark22@stanford.edu
      • Principal Investigator: Fred M Baik, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Cohort A - Unresectable or recurrent/metastatic head and neck cancer with at least 1 injectable tumor not scheduled for tumor resection surgery. With one the following prior treatments:

   Subjects must have received a platinum containing chemotherapy regimen, 5-Fluorouracil chemotherapy, taxane based chemotherapy, cetuximab or gemcitabine for treatment of primary tumor in locally advanced, or metastatic settings.

   Subjects must have received an anti-PD-1/ PD-L1 as monotherapy or in combination with chemotherapy.

   Subjects must have progressed following therapy with at least one PD-1 or PD-L1 checkpoint inhibitor (regardless of PD-L1 expression status).

   Prior progression on a PD-1 or PD-L1 checkpoint inhibitor should be unequivocal; progression that occurs within the first 8 weeks of treatment on these agents should be confirmed with a second CT at least 4 weeks apart (to exclude pseudo-progression).

   Patients with activating EGFR mutation or ALK rearrangement which is expected to be responsive to available tyrosine kinase inhibitor therapy, therefore these subjects must have been previously treated with an applicable tyrosine kinase inhibitor.

   OR Cohort C - Patients with at least 1 measurable resectable lesion clinical stage I-IVb (cT1-4, N0-3) (AJCC, 8th Edition) (Amin, 2017), Histologically or cytologically confirmed HNSCC. Scheduled to undergo tumor surgical resection of the primary tumor.

2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and adequate bone marrow and organ function.
3. Primary tumors should be amenable to intratumoral (IT) injection >1 cm diameter. This will be determined by the Protocol Director, or the surgeon involved.
4. Subjects with either a local recurrence or a new primary tumor will be allowed.
5. Age ≥ 18 years.

6. Have acceptable organ and marrow function defined as follows:

   Absolute neutrophil count ≥ 1,500/mcL Platelets ≥ 100,000/mcL Hemoglobin ≥ 8.0 g/dL (Note: use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable) Total bilirubin ≤2x institutional upper limit of normal (ULN) AST(SGOT) or ALT(SGPT) ≤ 3.0x institutional ULN

7. Ability to understand and the willingness to provide written informed consent.
8. Life expectancy > 12 weeks (about 3 months).
9. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

1. Tumors which are not feasible for injections include high risk lesions that are near vital organs or important neurovascular structures, as determined by the Protocol Director or involved surgeon.
2. Women of childbearing potential must have a negative serum β-hCG pregnancy test within 7 days prior to the administration of the first study treatment and/or urine pregnancy 48 hours prior to the administration of the first study treatment. Both sexually active women of childbearing potential and males (and their female partners) patients must agree to use two methods of effective contraception, one of them being a barrier method, or to abstain from sexual activity during the study and for at least 6 months after last dose of study drugs.
3. Patients expected to receive other anti-cancer medication such as, chemotherapy, immunotherapy, biologic therapy, targeted therapy, monoclonal antibodies, hormonal therapy (other than leuprolide or other GnRH agonists) prior to surgery and where all acute toxicity of prior treatments have not resolved.
4. Participation in another clinical study with an investigational product during the last 30 days.
5. Uncontrolled intercurrent illness including, that do not respond to active medical intervention.
6. Current or prior use of immunosuppressive medication within 28 days before the first dose of injection, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid.
7. If applicable: Women who are breastfeeding.
8. History of allogenic organ transplant that requires use of immunosuppressives.
9. Subject has active or uncontrolled infection including known HIV infection or known chronic hepatitis B or C.
10. Any condition that, in the investigator's opinion, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
11. Uncontrolled intercurrent illness including those that do not respond to active medical intervention.
12. Any contraindication to the use of known history of hypersensitivity to any immune therapy's drugs.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A (1 x 10^9 viral particles per injection); Recurrent or Metastatic Head and Neck Cancer not scheduled for tumor resection surgery, 4 doses VLPONC-01 administered IT once weekly, with an additional follow-up safety visit 30 and 90 days post the final injection.	Biological: VRP-encapsulated saRNA encoding IL-12 (1 x 10^9 viral particles per injection); Weekly IT injections of 1 x 10^9 viral particles of VLPONC-01; Other Names: VLPONC-01; IL-12 saRNA; VRP-IL-12
Experimental: Cohort C - Group 1 (1 x 10^9 viral particles per injection plus Pembrolizumab); Head and Neck Squamous Cell Carcinoma Patients scheduled for tumor resection surgery, 4 doses VLPONC-01 administered IT once weekly and 2 doses of 200mg neoadjuvant Pembrolizumab IV 3 weeks apart prior to tumor resection surgery, follow-up safety visit 30 days post-surgery and 90 days post final treatment.	Biological: VRP-encapsulated saRNA encoding IL-12 (1 x 10^9 viral particles per injection); Weekly IT injections of 1 x 10^9 viral particles of VLPONC-01; Other Names: VLPONC-01; IL-12 saRNA; VRP-IL-12; Drug: Pembrolizumab (KEYTRUDA®); 200mg twice 3 weeks apart IV; Other Names: Pembrolizumab
Experimental: Cohort C - Group 2 (3 x 10^8 viral particles per injection plus Pembrolizumab); Head and Neck Squamous Cell Carcinoma Patients scheduled for tumor resection surgery, 4 doses VLPONC-01 administered IT once weekly and 2 doses of 200mg neoadjuvant Pembrolizumab IV 3 weeks apart prior to tumor resection surgery follow-up safety visit 30 days post-surgery and 90 days post final treatment.	Drug: Pembrolizumab (KEYTRUDA®); 200mg twice 3 weeks apart IV; Other Names: Pembrolizumab; Biological: VRP-encapsulated saRNA encoding IL-12 (3 x 10^8 viral particles per injection); Weekly IT injections of 3 x 10^8 viral particles of VLPONC-01; Other Names: VLPONC-01; IL-12 saRNA; VRP-IL-12
Experimental: Cohort C - Pembrolizumab only; Head and Neck Squamous Cell Carcinoma Patients scheduled for tumor resection surgery, 2 doses of 200mg neoadjuvant Pembrolizumab IV 3 weeks apart prior to tumor resection surgery, follow-up safety visit 30 days post-surgery and 90 days post final treatment.	Drug: Pembrolizumab (KEYTRUDA®); 200mg twice 3 weeks apart IV; Other Names: Pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	To assess the safety and tolerability of VLPONC-01. Safety will be based on the occurrence of any grade 3 or higher drug-related adverse events from the VLPONC-01 injections for non-surgery patients and any grade 3 or higher drug-related adverse events that result in a delay to tumor resection surgery.	First injection to 90-day follow-up visit post-final injection (Cohort A) or post-surgery (Cohort B and Cohort C)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of circulating IL-12	To assess the circulating blood levels of IL-12 after VLPONC-01 treatment compared to baseline to determine the occurrence and safety profile of potential systemic inflammatory responses.	First injection to 30-day follow-up visit post-final injection (Cohort A) or post-surgery (Cohort B and Cohort C)
VLPONC-01 levels in tumor tissue	To detect levels of VLPONC-01 RNA in surgically resected tissue.	First injection to tumor resection surgery
Tumor response	To assess the primary tumor response by radiological imaging and pathological analysis.	First injection to tumor resection surgery

Collaborators and Investigators

• Sponsor: VLP Therapeutics
• Collaborators: Stanford University
• Investigators: Principal Investigator: Fred M Baik, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: December 11, 2024
• First Submitted That Met QC Criteria: December 11, 2024
• First Posted (Actual): December 16, 2024

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Keytruda; pembrolizumab; Intratumoral; anti-PD-1; IT injection; IL-12; macrophage; tumor resection; saRNA; Interleukin 12; VLP; Virus-like particle; VRP; Viral Replicon Particle; VRP-encapsulated; tumor resection surgery; Self-amplifying RNA; Multiple inoculations directly into the tumor; viral particles per injection; viral particles
• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Mouth Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Adjuvants, Immunologic; pembrolizumab
• Other Study ID Numbers: VLPONC-01; SYNERNA-01 (Other Identifier: VLP Therapeutics, Inc.)

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No