Recruiting
Phase 2

RP2

Sponsor:

Glenn J. Hanna

Code:

NCT06623110

Conditions

High-Risk Oral Precancerous Disease

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

RP2 Injection

Study Details

Brief summary:

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 conditions and prevent progression to an oral cancer.

The name of the study drug involved in this study is:

-RP2 (a genetically modified live Herpes Simplex V-1 strain)

Conditions

High-Risk Oral Precancerous Disease

Study ID

NCT06623110

Start date

Jan 1, 2025

Status verified date

Apr, 2026

Completion date

Jan 1, 2029

Anticipated

Primary completion date

Jan 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Patients with a diagnosis of high-risk OPD defined by any of the following:

  • Proliferative leukoplakia (PL)
  • Localized leukoplakia showing at least moderate dysplasia not treated with surgery
  • Erythroplakia (regardless of dysplasia)
  • High-risk LOH profile: 9p21 or CDKN2A or MTAP loss; regardless of personal oral cancer history
  • Any degree of dysplasia with a known TP53 mutation
  • A history of treated stage 1 or 2 (AJCC 2017 8th edition) HNSCC with at least moderate dysplasia at the resection margins or known 9p21 loss or a known TP53 mutation
  • No evidence of head and neck cancer recurrence within the last 3 months (if applicable).
  • Willing to provide blood and tissue for diagnostic biopsies.
  • At least one target injectable measurable lesion ≥1 cm in longest diameter that can be followed.
  • Any smoking history is permitted. While discouraged, patients are permitted to continue tobacco use while on the study.
  • Age 18 years or older at the time of consent.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  • Participant must have normal marrow function and coagulation profile as defined within 21 days prior to study registration:

  • absolute neutrophil count ≥1,000/mcL
  • hemoglobin ≥9 g/dL
  • platelets ≥75,000/mcL, and (d) PT/INR <2.5, and (e) aPTT <1.5x ULN.
  • Women of childbearing potential (WOCBP) must agree to use appropriate method(s) of contraception. WOCBP and men should plan to use an adequate method to avoid pregnancy for 90 days after the last dose of RP2. WOCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Serum or urine BhCG testing is required within 24 hours of initial RP2 dosing.

Exclusion Criteria:

  • Prior treatment with an oncolytic virus therapy.
  • Systemic infection requiring intravenous (IV) antibiotics.
  • Requires chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (e.g. acyclovir or valacyclovir).
  • Active significant herpetic infections or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis). Patients with sporadic cold sores may be enrolled provided they are asymptomatic at the time of starting RP2.
  • Known acute or chronic hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or acute or chronic hepatitis C virus (defined as HCV RNA \[qualitative\] is detected). Note: Patients who have been effectively treated are eligible for enrollment. Patients must be negative for HBsAg and HCV RNA.
  • Known human immunodeficiency virus (HIV) infection. Note: Testing for HIV is not required unless mandated by local health authority or clinically indicated.
  • A history of a prior stage III (T1-2N1, T3N0) or IV (T1-3N2, T4N0) invasive head \& neck squamous cell carcinoma treated with surgery and/or radiation with or without chemotherapy.
  • Patients cannot be on long-term (>4 weeks) corticosteroids at doses exceeding prednisone 20 mg daily (or its equivalent) at the time of enrollment.
  • A personal history of hematopoietic stem cell (bone marrow) or solid organ transplant.
  • A personal history of other active malignancies, with exceptions including (but not limited to): non-melanomatous skin cancers, low-risk prostate adenocarcinoma on active surveillance, or treated cancers in remission for the last 2 years.
  • Significant bleeding event within the last 6 months that places the patient at risk for bleeding due to the injection procedure based on Investigator assessment.

Study Design

Enrollment

25 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: RP2 Injection

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.

Interventions

RP2 Injection

Genetically modified live HSV-1 virus, 3.0 mL single-use glass vials, via intralesional (into a lesion) injection per protocol.

Primary outcome measure

  • Best Overall Response [ Time Frame: Up to 1 year ]

Central Contacts and Locations

Central contacts

Glenn Hanna, MD

617-632-3090glenn_hanna@dfci.harvard.edu

Locations

Brigham and Women's Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Glenn J Hanna, MD

617-632-3090glenn_hanna@dfci.harvard.edu

Principal Investigator:

Glenn J Hanna, MD

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Glenn J Hanna, MD

617-632-3090glenn_hanna@dfci.harvard.edu

Principal Investigator:

Glenn J Hanna, MD

More Information

Sponsor

Glenn J. Hanna

Last update posted

Apr 23, 2026

Last verified

Apr, 2026

Keywords

  • High-Risk Oral Precancerous Disease
  • Oral Precancerous Disease

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Glenn J. Hanna on 2026-04-23.