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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for head and neck cancer to assess its safety and effectiveness. Researchers are testing a treatment that combines a virus-based injection (VRP-encapsulated saRNA encoding IL-12) with the cancer drug pembrolizumab. The goal is to determine if this combination can shrink tumors more effectively than the drug alone. Individuals with head and neck cancer, whose tumors can be injected or surgically removed, might be suitable for this trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown pembrolizumab to be safe. The FDA has already approved it for treating certain types of head and neck cancer. Patients have received pembrolizumab in various situations, and it has generally been well-tolerated. Common side effects include fatigue and skin rash, but these are often manageable.

The VRP-encapsulated saRNA encoding IL-12 treatment is newer, requiring more research to fully understand its safety in humans. This trial is in an early phase, focusing primarily on safety assessment. Early trials typically start with small groups to closely monitor any side effects. Currently, there isn't enough data to draw conclusions about its safety. However, its presence in a clinical trial indicates researchers believe in its potential and are committed to thorough study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for head and neck cancer because they use viral replicon particles (VRP) to deliver self-amplifying RNA (saRNA) that encodes the immune-stimulating protein IL-12 directly into tumors. This method is different from the standard care options like surgery, radiation, and chemotherapy, as it aims to boost the body's immune response specifically at the tumor site. Additionally, some treatment arms combine VRP with Pembrolizumab, an existing immunotherapy drug, which could enhance the overall effectiveness by targeting cancer cells in multiple ways. This innovative approach may offer a more targeted and potentially less toxic treatment option compared to traditional therapies.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

This trial will evaluate different treatment approaches for head and neck cancer. Some participants will receive pembrolizumab, which studies have shown can effectively treat head and neck squamous cell carcinoma. It has been proven to help patients live longer and delay cancer recurrence. Research indicates that adding pembrolizumab to standard treatments significantly improves patient outcomes.

Other participants will receive VRP-encapsulated saRNA encoding IL-12. Early animal studies suggest this treatment might control tumors better than some other methods. This approach uses a special kind of RNA (a molecule that helps make proteins) to activate the body's immune system to fight cancer cells. Although data collection from human studies is ongoing, this method shows promise in directly boosting the immune response against the tumor. ^{4 6 7 8 9}

Who Is on the Research Team?

Fred M Baik, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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 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+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36219809/

Updated Results of the Phase III KEYNOTE-048 Study - PubMed Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2415434

Neoadjuvant and Adjuvant Pembrolizumab in Locally ... The addition of neoadjuvant and adjuvant pembrolizumab to standard care significantly improved event-free survival among participants with locally advanced ...

3. merck.com merck.com/news/european-commission-approves-keytruda-pembrolizumab-as-part-of-a-treatment-regimen-for-adults-with-resectable-locally-advanced-head-and-neck-squamous-cell-carcinoma-la-hnscc-expressing-pd-l1/

European Commission Approves KEYTRUDA® ... European Commission Approves KEYTRUDA® (pembrolizumab) as Part of a Treatment Regimen for Adults with Resectable Locally Advanced Head and Neck ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02252042

Study Details | NCT02252042 | Pembrolizumab (MK-3475) ... The primary study hypothesis is that pembrolizumab treatment prolongs Overall Survival (OS) when compared to standard treatment. Official Title. A Phase III ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6012

Neoadjuvant and adjuvant pembrolizumab plus standard ... The randomized phase 3 KEYNOTE-689 study (NCT03765918) showed significantly improved event-free survival (EFS) with neoadjuvant/adjuvant pembrolizumab + SOC vs ...

6. keytruda.com keytruda.com/head-and-neck-cancer/

Head and Neck Squamous Cell Cancer FDA-APPROVED FOR PEOPLE WITH CERTAIN TYPES OF HEAD AND NECK SQUAMOUS CELL CANCER · Understanding KEYTRUDA · Treatment information and clinical trial results · What ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e14593

Safety of pembrolizumab in advanced head and neck ... However, its safety profile in Head and Neck Squamous Cell Carcinoma (HNSCC) remains inadequately studied. ... pembrolizumab for renal cell ...

8. fda.gov fda.gov/drugs/resources-information-approved-drugs/pembrolizumab-keytruda

pembrolizumab (KEYTRUDA) Safety data was evaluated in 192 patients with HNSCC receiving at least one dose of pembrolizumab 10 mg/kg every 2 weeks or 200 mg every 3 weeks ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5507654/

FDA Approval Summary: Pembrolizumab for the Treatment of ... This article summarizes the evidence for the impact of BRAF mutations on treatment outcome of anti‐EGFR monoclonal antibodies.