RP1 for Skin Cancer

Overseen By Catherine VanHooft, HT

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sherrif Ibrahim

Must not be taking: Antivirals, Immunosuppressants, Antibiotics, others

Disqualifiers: Visceral metastases, Autoimmune disease, Cardiovascular disease, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment called RP1 (vusolimogene oderparepvec) for individuals with cutaneous Squamous Cell Carcinoma, a type of skin cancer. The goal is to determine if RP1 is safe and effective when injected directly into surgically removable skin tumors. Individuals diagnosed with this type of skin cancer who have not yet received other treatments for their tumors might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use antiviral medications with antiherpetic activity or botanical preparations during the study.

Is there any evidence suggesting that RP1 is likely to be safe for humans?

Research has shown that RP1, a treatment being tested for skin cancer, is generally safe for people. Studies have found that RP1 leaves the blood and urine quickly, making it unlikely to spread to others or the environment. This finding reassures both patients and those around them.

In another study with skin cancer patients who received RP1 along with another drug, researchers examined unwanted side effects. No major safety issues emerged, suggesting that RP1 is well-tolerated.

RP1, also known as vusolimogene oderparepvec, has also been studied in other types of skin cancer, with no significant safety concerns identified. This adds to the confidence in the safety of RP1 for those considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for skin cancer, which often involve surgery, radiation, or chemotherapy, RP1 offers a new approach by using a modified virus to attack cancer cells directly. Researchers are excited about RP1 because it is administered through direct intratumoral injection, meaning it's injected right into the tumor, which can potentially increase its effectiveness while minimizing side effects. RP1 also works by triggering the body's immune system to recognize and destroy cancer cells, offering a dual mechanism of action that could lead to better outcomes for patients with cutaneous squamous cell carcinoma (CSCC).

What evidence suggests that RP1 might be an effective treatment for skin cancer?

Research shows that RP1, which participants in this trial will receive, has promising results for treating some skin cancers. RP1 is a modified herpes virus that can destroy cancer cells. Studies have shown it can effectively target and shrink tumors in people with melanoma, a type of skin cancer. In earlier trials, RP1 effectively reduced tumors and was generally safe for patients. While more research is needed for cutaneous Squamous Cell Carcinoma (CSCC), these early results offer hope for its potential in treating this condition. ^{1 4 6 7 8}

Who Is on the Research Team?

Catherine VanHooft, HT

Principal Investigator

Rochester Dermatologic Surgery

Are You a Good Fit for This Trial?

This trial is for adults over 18 with resectable cutaneous Squamous Cell Carcinoma who haven't had treatment on the target lesion. They should be in good health, have a life expectancy over 2 years, and tumors between 1.0 and 3.0 cm in size that are visible and can be measured.

Inclusion Criteria

My targeted cancer area has not received any treatment.

My blood clotting levels are within a normal range.

Anticipated life expectancy > 2 years

Exclusion Criteria

My tumor's edges are not clearly defined.

Documented history of allergic reactions or acute hypersensitivity reaction attributed to RP1 or to any of the excipients

Patients with a history of any positive test result for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating the presence of the virus, or human immunodeficiency virus (HIV) positive

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive RP1 via direct intratumoral injection into superficial cutaneous solid tumors to assess safety, tolerability, and efficacy

16 weeks

Multiple visits for intratumoral injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Long-term follow-up

Participants are monitored for progression-free survival and other secondary outcomes

2 years

What Are the Treatments Tested in This Trial?

Interventions

• RP1

Trial Overview The study tests RP1, an investigational drug given by direct injection into the tumor of patients with Squamous Cell Carcinoma. It aims to evaluate its safety, tolerability, and effectiveness in up to 12 participants.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Patients will receive RP1 via direct intratumoral (IT) injection into superficial cutaneous solid tumors to assess the safety and tolerability as well efficacy of RP1 treatment. The primary efficacy population is up to 12 evaluable patients with resectable CSCC.

RP1 is already approved in United States for the following indications:

Approved in United States as vusolimogene oderparepvec for:

• Advanced melanoma in patients who have previously received an anti-PD1 containing regimen

Who Is Running the Clinical Trial?

Sherrif Ibrahim

Lead Sponsor

Trials

1

Recruited

10+

Published Research Related to This Trial

Talimogene laherparepvec (T-VEC) is the first oncolytic viral therapy approved by the FDA for treating advanced melanoma with unresectable skin and lymph node lesions.

The approval was based on data from the OPTiM study, highlighting T-VEC's efficacy in targeting and destroying cancer cells while sparing normal tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Oncolytic Viral Therapy for Melanoma. Poh, A.[2017]

Talimogene laherparepvec, an oncolytic herpes virus, is effective for treating unresectable melanoma lesions, administered through intralesional injections.

In two cases, patients showed persistent lesions on imaging but had no evidence of disease upon surgical excision, suggesting that imaging may not always accurately reflect treatment success, and these patients remain in durable remission after stopping treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Challenges with Talimogene Laherparepvec: Cured Lymph Nodes Masquerading as Active Melanoma. Swami, U., Swick, B., Zakharia, Y., et al.[2020]

NRP1 is expressed in the differentiated layers of human and mouse skin, specifically in keratinocytes, indicating its potential role in skin biology and differentiation.

The expression of NRP1 is regulated by factors such as UVB irradiation and growth factors, suggesting it may help modulate the activity of VEGF in epithelial cells, which could have implications for skin health and cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas. Shahrabi-Farahani, S., Wang, L., Zwaans, BM., et al.[2023]

Combining talimogene laherparepvec (T-VEC) with MEK inhibition showed enhanced therapeutic effects in mouse models of melanoma, suggesting a promising treatment strategy.

The combination therapy not only increased viral replication but also boosted PD-1/PD-L1 expression, indicating that adding PD-1 blockade could further improve tumor regression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triple threat to cancer: rationale for combining oncolytic viruses, MEK inhibitors, and immune checkpoint blockade. Bommareddy, PK., Rabkin, SD., Kaufman, HL.[2021]

The combination of the oncolytic virus T-VEC and the MEK inhibitor trametinib significantly enhances melanoma cell death and improves survival in mouse models, indicating a promising therapeutic strategy.

This combination therapy activates CD8+ T cells and dendritic cells, leading to tumor regression and increased expression of PD-L1, suggesting that adding anti-PD-1 antibodies could further improve treatment outcomes in melanoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEK inhibition enhances oncolytic virus immunotherapy through increased tumor cell killing and T cell activation. Bommareddy, PK., Aspromonte, S., Zloza, A., et al.[2021]

Talimogene laherparepvec (T-VEC) is an innovative oncolytic virus approved by the FDA for treating melanoma, showing a higher durable response rate compared to traditional treatments in a phase III trial.

T-VEC works by directly destroying cancer cells and also acts as an 'in situ vaccine,' enhancing the body's immune response, and is currently being tested in combination with other therapies for various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talimogene Laherparepvec for the Treatment of Advanced Melanoma. Ott, PA., Hodi, FS.[2021]

In the phase III OPTiM trial involving 436 patients with advanced melanoma, talimogene laherparepvec (T-VEC) led to a significant reduction in size of injected lesions (64% showed a decrease of ≥50%) and also demonstrated systemic effects by reducing the size of uninjected lesions (34% of non-visceral lesions).

The study found that while some patients experienced progression prior to response (PPR), this did not negatively affect the overall clinical effectiveness of T-VEC, indicating that the treatment can still be effective even if new lesions appear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial. Andtbacka, RH., Ross, M., Puzanov, I., et al.[2021]

In a study of 83 melanoma patients, talimogene laherparepvec (T-VEC) was used in various ways: alone, after anti-PD-1 therapy, or alongside it, showing flexibility in treatment approaches.

About 25% of patients stopped T-VEC because they had no more injectable lesions, while 37% discontinued due to disease progression, indicating that T-VEC can be effectively integrated into treatment plans but may not prevent disease advancement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observational study of talimogene laherparepvec use in the anti-PD-1 era for melanoma in the US (COSMUS-2). Sun, J., Gastman, BR., McCahon, L., et al.[2022]

Citations

1. ir.replimune.com ir.replimune.com/news-releases/news-release-details/replimune-provides-data-update-its-rp1-vusolimogene-oderparepvec

Replimune Provides Data Update from its RP1 ... RP2 data confirms the signal with RP1 in anti-PD1 failed melanoma, uveal melanoma and in treating patients whose cancer has metastasized to the liver.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.9534

Biosafety analysis from the skin cancer cohorts in ... These data demonstrate that RP1 is rapidly cleared from blood and urine, with negligible likelihood of environmental dissemination or transfer to contacts.

3. targetedonc.com targetedonc.com/view/rp1-and-the-future-of-oncolytic-therapy-in-melanoma

RP1 and the Future of Oncolytic Therapy in Melanoma RP1 (vusolimogene oderparepvec) is a genetically engineered next-generation herpes simplex virus that is intended to lyse tumor cells.

4. oncologynewscentral.com oncologynewscentral.com/melanoma/fda-rejects-oncolytic-virus-combination-for-advanced-melanoma

FDA Rejects Oncolytic Virus Combination for Advanced ... We strongly believe that RP1 in combination with nivolumab can bring substantial benefit to advanced melanoma patients.” The application was ...

5. ejcskn.com ejcskn.com/article/S2772-6118(25)00420-3/fulltext

Safety and efficacy results from an open-label phase 1b/2 ... RP1 showed compelling anti-tumor activity in evaluable pts and was well tolerated, with a safety profile similar to that reported in non-immunocompromised pts ...

6. ir.replimune.com ir.replimune.com/news-releases/news-release-details/replimune-announces-positive-initial-data-anti-pd1-failed

Release Details The data from the first 75 patients in the new cohort showing an overall 36% ORR, a 20% CR rate, and clinically meaningful activity across all sub-groups ...

7. onclive.com onclive.com/view/rp1-plus-nivolumab-elicits-responses-in-melanoma-after-progression-on-anti-pd-1-therapy

RP1 Plus Nivolumab Elicits Responses in Melanoma After ... Regarding safety data for all patients with skin cancer who have received RP1 plus nivolumab during IGNYTE (n = 187), treatment-related adverse ...

8. drugs.com drugs.com/history/vusolimogene-oderparepvec.html

Vusolimogene oderparepvec FDA Approval Status Importantly, no safety issues were raised. Vusolimogene oderparepvec is also being studied in non-melanoma skin cancer. Add as a preferred ...