Phase II Study of RP2 as Immunoprevention in High-Risk Oral Precancerous Disease

NCT06623110 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-383
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

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

Keywords

High-Risk Oral Precancerous Disease; Oral Precancerous Disease

Outcome Measures

Primary Outcomes (1)

• Best Overall Response

  The best overall response is the best response recorded from the start of the treatment until disease progression (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Responses do not require confirmation. Complete response (CR) is complete disappearance of all target lesions. Partial response (PR) is at least 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Up to 1 year

Secondary Outcomes (3)

• Adverse Event Rate

  Up to 1 year

• Median Cancer-free Survival (CFS)

  Up to 1 year

• Median Overall Survival (OS)

  Up to 3 years

Study Arms (1)

RP2 Injection

EXPERIMENTAL

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.

Biological: RP2 Injection

Interventions

RP2 Injection BIOLOGICAL

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

RP2 Injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Glenn J. Hanna: lead
• Replimune, Inc.: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Study Officials

• Glenn Hanna, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Glenn Hanna, MD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: September 30, 2024
• First Posted: October 2, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)