RP2 Injection for Oral Leukoplakia

(INTERCEPT Trial)

Recruiting at 1 trial location

Overseen By Glenn Hanna, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Glenn J. Hanna

Must not be taking: Antivirals, Corticosteroids

Disqualifiers: HIV, Hepatitis B/C, Transplant, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 13

Duration: 16 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called RP2, an injected immune therapy made from a modified virus, to determine its safety in treating early warning signs of mouth cancer. The goal is to prevent oral precancer conditions from developing into full-blown cancer. The trial seeks individuals diagnosed with certain high-risk oral conditions, such as leukoplakia or erythroplakia, which indicate potential changes in the mouth that could lead to cancer. Participants should have at least one measurable lesion (a patch or sore) in their mouth that can be tracked throughout the study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain antivirals like acyclovir or valacyclovir. If you are on long-term corticosteroids, the dose must not exceed prednisone 20 mg daily.

Is there any evidence suggesting that RP2 is likely to be safe for humans?

Research has shown that RP2, a genetically modified herpes simplex virus, has been tested in humans and has a good safety record. In earlier studies, RP2 did not cause severe side effects that halted the study, allowing the treatment to be administered without major issues.

RP2 has been tested for its tumor-fighting ability, and similar treatments have been well-tolerated. However, RP2 is still under investigation for safety and effectiveness in treating early-stage oral cancer conditions. While early results are promising, further research is necessary to confirm that RP2 is safe and effective for all patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

RP2 is unique because it offers a novel approach to treating oral leukoplakia by using a specialized injection directly targeting the affected oral mucosa. Unlike traditional treatments, such as surgical removal or laser therapy, RP2 works by potentially harnessing the body's immune response to address the abnormal cells more directly and effectively. Researchers are excited about RP2 because it could provide a less invasive option with potentially fewer side effects and a more targeted action, which might improve patient outcomes and comfort compared to existing treatments.

What evidence suggests that RP2 might be an effective treatment for oral leukoplakia?

Research has shown that RP2, a modified herpes virus, could be a promising cancer treatment. In earlier studies, RP2 shrank or eliminated tumors by enhancing the body's immune response against cancer cells. It contains GM-CSF, a protein that boosts the immune system, and an anti-CTLA-4 antibody, which helps the immune system better identify and attack cancer cells. In this trial, participants will receive RP2 injections to evaluate its potential as a treatment for oral precancers and possibly prevent them from turning into cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Glenn J. Hanna, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with oral leukoplakia, a condition that can lead to mouth cancer. Participants should be at high risk of their condition progressing to cancer but have not yet developed it.

Inclusion Criteria

Willing to provide blood and tissue for diagnostic biopsies

I have a tumor that can be measured and is at least 1 cm big.

I have been diagnosed with high-risk osteoporosis.

Exclusion Criteria

Active significant herpetic infections or prior complications of HSV-1 infection

I had stage III or IV head & neck cancer before.

I have been treated with a virus-based cancer therapy before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive RP2 injections every 2 weeks with in-clinic visits and assessments

16 weeks

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• RP2

Trial Overview The study tests the safety and potential effectiveness of RP2 injections, which is a modified herpes virus aimed at preventing oral precancerous conditions from becoming cancerous.

How Is the Trial Designed?

Group I: RP2 Injection Experimental Treatment 1 Intervention

Enrolled participants will complete the following: * A 3 subject safety run-in will be conducted with participants enrollment staggered. If \> 1 subject experiences a grade 4-5 adverse event (AE), study enrollment will pause for review by PI and study sponsor. If there are 0 grade 4-5 AEs, enrollment will proceed. * Baseline in-clinic visit with assessments, oral mucosal punch biopsy, and RP2 injection (week 1). * In-clinic visits on weeks 3, 5, 7, 8, 9, 11, 13, 15, and 16. * RP2 injections on weeks 1, 3, 5, 7, 9, 11, 13, and 15. * Repeat oral mucosal punch biopsy at week 8. * Follow up: every 3 months for up to 2 years.

Who Is Running the Clinical Trial?

Glenn J. Hanna

Lead Sponsor

Trials

6

Recruited

160+

Replimune Inc.

Industry Sponsor

Trials

16

Recruited

1,700+

Published Research Related to This Trial

G207, a modified herpes simplex virus, was safely administered to 21 patients with malignant gliomas, with doses escalating from 10^6 to 3x10^9 plaque forming units, and no serious adverse events linked to the treatment were observed.

The study provided early evidence of anti-tumor activity, as indicated by radiographic and neuropathologic findings, along with the long-term presence of viral DNA in some patients, suggesting potential therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. Markert, JM., Medlock, MD., Rabkin, SD., et al.[2023]

Citations

1. dana-farber.org dana-farber.org/clinical-trials/24-383

A Phase 2 Study of Intralesional RP2 as Immunoprevention ... The goal of this study is to understand the safety, tolerability, and potential efficacy of an injected immune therapy called RP2 to treat oral precancer ...

2. asco.org asco.org/abstracts-presentations/ABSTRACT368930

A phase 1 trial of RP2, a first-in-class, enhanced potency ... RP2 has demonstrated antitumor activity in preclinical models using viruses similar to RP2 expressing murine versions of anti-CTLA-4 and GM-CSF, both alone and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12390425/

Oncolytic Herpes Simplex Virus Therapy: Latest Advances ... Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment.

4. researchgate.net researchgate.net/publication/357151079_507_A_phase_1_clinical_trial_of_RP2_an_enhanced_potency_oncolytic_HSV_expressing_an_anti-CTLA-4_antibody_as_a_single_agent_and_combined_with_nivolumab_in_patients_with_advanced_solid_tumors

507 A phase 1 clinical trial of RP2, an enhanced potency ... RP2 is an enhanced-potency oncolytic HSV-1 that expresses GM-CSF, an anti-CTLA-4 antibody-like molecule, and the fusogenic gibbon ape leukemia ...

5. onclive.com onclive.com/view/herpes-simplex-1-oncolytic-showcases-antitumor-activity-across-heavily-pretreated-solid-tumors

Herpes Simplex-1 Oncolytic Showcases Antitumor Activity ... Initial results of a phase 1 trial of RP2, a first in class, enhanced potency, anti-CTLA-4 antibody expressing, oncolytic HSV as single ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11804204/

Oncolytic virus OH2 extends survival in patients with PD-1 ... OH2 oncolytic virotherapy exhibited a favorable safety profile without dose-limiting toxicities (DLTs) and demonstrated durable antitumor ...

7. trial.medpath.com trial.medpath.com/clinical-trial/7a5d02a3aa5a41a7/nct06623110-phase-2-study-intralesional-rp2-oral-precancerous-disease

Phase II Study of RP2 as Immunoprevention in High-Risk Oral ... The goal of this study is to understand the safety, tolerability, and potential efficacy of an injected immune therapy called RP2 to treat oral precancer ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5405200/

Presage of oncolytic virotherapy for oral cancer with herpes ... Melanoma in the oral cavity is the target of oncolytic HSV-1. Oncolytic virotherapy is a hopeful and realistic modality for the treatment of oral cancer.