Viral Replicon Particles for Head and Neck Cancer

Overseen By Clinical Research Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: VLP Therapeutics

Must be taking: Anti-PD-1, PD-L1 inhibitors

Must not be taking: Immunosuppressives, Chemotherapy

Disqualifiers: Uncontrolled illness, Active infection, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 30

Duration: 4-6 weeks

41 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving other anti-cancer medications or immunosuppressive drugs within 28 days before the first dose of the trial treatment.

What data supports the effectiveness of this treatment for head and neck cancer?

Research shows that using IL-12, a part of this treatment, can help the immune system fight tumors effectively in animal models. In particular, IL-12 has been shown to reduce tumor size and create a strong immune response against cancer cells, suggesting potential benefits for head and neck cancer treatment. ^{1 2 3 4 5}

How is the treatment VRP-encapsulated saRNA encoding IL-12 different from other treatments for head and neck cancer?

This treatment is unique because it uses viral replicon particles to deliver self-replicating RNA that encodes IL-12, a protein that helps boost the immune system. Unlike traditional treatments, it is designed to be injected directly into the tumor, promoting a strong immune response and potentially eradicating tumors with a single dose. ^{2 3 6 7 8}

What is the purpose of this trial?

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 Squamous Cell Carcinomas 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.

Research Team

Fred M Baik, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for individuals with specific types of head and neck cancers, including squamous cell carcinoma and esophageal carcinoma. Participants should have a tumor suitable for injection. Details on who can join are not fully provided here.

Inclusion Criteria

Ability to understand and the willingness to provide written informed consent

Life expectancy > 12 weeks (about 3 months)

Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

Exclusion Criteria

Participation in another clinical study with an investigational product during the last 30 days

If applicable: Women who are breastfeeding

Any condition that, in the investigator's opinion, would interfere with evaluation of study treatment or interpretation of patient safety or study results

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intratumoral injections of VLPONC-01, with some cohorts also receiving neoadjuvant pembrolizumab

4-6 weeks

Weekly visits for injections

Surgery

Participants in certain cohorts undergo tumor resection surgery after receiving treatment

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment and surgery

90 days

Follow-up visits at 30 and 90 days post-treatment or post-surgery

Treatment Details

Interventions

• Pembrolizumab
• VRP-encapsulated saRNA encoding IL-12

Trial Overview The study tests the safety of injecting VRP-encapsulated saRNA encoding IL-12 into tumors, alone or combined with pembrolizumab (KEYTRUDA®), to see if it improves tumor response in head and neck cancer patients.

Participant Groups

Group I: Cohort C - Pembrolizumab only Experimental Treatment 1 Intervention

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.

Group II: Cohort C - Group 2 (3 x 10^8 viral particles per injection plus Pembrolizumab) Experimental Treatment 2 Interventions

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.

Group III: Cohort C - Group 1 (1 x 10^9 viral particles per injection plus Pembrolizumab) Experimental Treatment 2 Interventions

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.

Group IV: Cohort B (1 x 10^9 viral particles per injection) Experimental Treatment 1 Intervention

Head and Neck Squamous Cell Carcinoma Patients scheduled for tumor resection surgery, 2 doses VLPONC-01 administered IT once weekly prior to tumor resection surgery, follow-up safety visit 30 days post-surgery and 90 days post final injection.

Group V: Cohort A (1 x 10^9 viral particles per injection) Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

VLP Therapeutics

Lead Sponsor

Trials

2

Recruited

80+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Intratumoral expression of IL-12 from lentiviral or RNA vectors acts synergistically with TLR4 agonist (GLA) to generate anti-tumor immunological memory. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Multifunctional oncolytic nanoparticles deliver self-replicating IL-12 RNA to eliminate established tumors and prime systemic immunity. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Alloantigen gene therapy for squamous cell carcinoma of the head and neck: results of a phase-1 trial. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Cure of syngeneic carcinomas with targeted IL-12 through obligate reprogramming of lymphoid and myeloid immunity. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Combination nonviral interleukin 2 and interleukin 12 gene therapy for head and neck squamous cell carcinoma. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Oncolysis using herpes simplex virus type 1 engineered to express cytosine deaminase and a fusogenic glycoprotein for head and neck squamous cell carcinoma. [2021]

7. China pubmed.ncbi.nlm.nih.gov

[Reporter genes transfer into human squamous cell carcinoma of larynx factor receptor mediated non-viral GE7 polypeptide delivery system with a new epidermal growth]. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Intra-cheek immunization as a novel vaccination route for therapeutic vaccines of head and neck squamous cell carcinomas using plasmo virus-like particles. [2021]