RP1 for Melanoma

Overseen By Danielle Bednarz, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yana Najjar

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Hepatitis, HIV, Herpetic infections, 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: 3

Duration: 4-5 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 Vusolimogene Oderparepvec (also known as RP1), which uses a modified virus to fight melanoma, a type of skin cancer. The treatment targets and destroys tumor cells while sparing healthy ones, potentially activating the body's immune system to attack cancer cells. Individuals with a specific type of melanoma that shows visible tumors after a biopsy may be suitable for this study. As an Early Phase 1 trial, participants will be among the first to receive this innovative treatment, aiding researchers in understanding its effects in people.

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 participate if you are on immunosuppressive doses of corticosteroids or have received a live vaccine within 30 days before the study starts.

Is there any evidence suggesting that Vusolimogene Oderparepvec (RP1) is likely to be safe for humans?

Research has shown that vusolimogene oderparepvec (RP1) targets and kills cancer cells while sparing healthy ones. This modified virus specifically attacks and breaks down tumor cells, aiming to boost the body's immune system to fight cancer.

The current study is in its early stages, so information about side effects in humans may be limited. However, reaching this phase suggests that earlier tests demonstrated sufficient safety for human trials. These early trials are crucial for assessing safety and will closely monitor for any issues.

For those considering joining the trial, it is reassuring that RP1 is designed to avoid healthy cells. However, as with any new treatment, unknowns may exist. Participants will be closely monitored for any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Vusolimogene oderparepvec (RP1) is unique because it uses a genetically modified virus to target melanoma cells directly. Unlike traditional treatments like chemotherapy or radiation, which attack both healthy and cancerous cells, RP1 specifically infects and destroys tumor cells while sparing normal tissue. Researchers are excited about this treatment because it not only aims to eliminate melanoma cells but also stimulates the immune system to recognize and attack any remaining cancer. This dual action offers a promising new approach that could enhance the effectiveness and precision of melanoma treatment.

What evidence suggests that Vusolimogene Oderparepvec might be an effective treatment for melanoma?

Research has shown that Vusolimogene Oderparepvec, also known as RP1, could effectively treat melanoma, a type of skin cancer. This treatment uses a modified virus similar to the one causing cold sores, designed to attack and destroy cancer cells while leaving healthy cells unharmed. When RP1 enters a cancer cell, it multiplies and causes the cell to burst, releasing substances that alert the immune system to attack the cancer. Early results suggest that RP1 not only destroys the tumor it is injected into but may also help the immune system fight other cancer cells in the body. Although more data is needed, this method shows promise, especially for melanoma cases where other treatments have not succeeded. Participants in this trial will receive RP1 injections at specified intervals before undergoing surgery. ^{1 2 4 5 6}

Who Is on the Research Team?

Yana Najjar, MD

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with primary melanoma, specifically to reduce the risk of cancer spreading to sentinel lymph nodes. Participants must meet certain health criteria not specified here.

Inclusion Criteria

I am not pregnant, as confirmed by sensitive blood and urine tests.

I am fully active or restricted in physically strenuous activity but can do light work.

My organ functions are within normal ranges as per recent tests.

Exclusion Criteria

Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within four weeks prior to the first dose of study treatment

Has known psychiatric, alcohol abuse, or substance abuse disorders that would interfere with cooperating with the requirements of the study

I have not received a live vaccine in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 3 doses of RP1 injected into the skin at the tumor biopsy site at baseline (day 1), day 15, and day 21

4-5 weeks

3 visits (in-person)

Surgery

Definitive surgery including wide local excision and sentinel lymph node biopsy

1 week

Follow-up

Participants are monitored for recurrence of disease and adverse events

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Vusolimogene Oderparepvec (RP1)

Trial Overview The study tests Vusolimogene Oderparepvec (RP1), a modified herpes virus designed to target and kill melanoma cells while boosting the immune system's response against the tumor.

How Is the Trial Designed?

Group I: Vusolimogene oderparepvec (RP1) Experimental Treatment 1 Intervention

Patients will receive 3 doses of RP1 (1.0 mL/injection; 10e6 PFU/mL for the first dose, and 10e7 mL for the subsequent 2 doses). The drug will be injected into the skin at the tumor biopsy site at baseline (day 1), day 15, and day 21, 4-5 weeks prior to SOC WLE and SLNB. Definitive surgery will occur up to 28-35 (± 2 days) days from first injection, to avoid treatment delay.

Vusolimogene Oderparepvec (RP1) is already approved in United States for the following indications:

Approved in United States as RP1 for:

• Advanced melanoma (under review)

Who Is Running the Clinical Trial?

Yana Najjar

Lead Sponsor

Trials

7

Recruited

200+

Replimune Inc.

Industry Sponsor

Trials

16

Recruited

1,700+

Published Research Related to This Trial

Talimogene laherperepvec (T-VEC) is an injectable oncolytic herpes virus that has shown promising efficacy in treating advanced melanoma, with improved durable response rates and a tolerable side-effect profile in Phase II and III clinical trials.

While T-VEC is effective for melanoma, it has shown limited responses in patients with visceral metastases, and is currently being tested in combination with other immune therapies like ipilimumab and pembrolizumab for potentially enhanced effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talimogene laherparepvec (T-VEC) for the treatment of advanced melanoma. Johnson, DB., Puzanov, I., Kelley, MC.[2020]

Talimogene laherparepvec (OncoVEXmGM-CSF) demonstrated significant efficacy in treating melanoma, curing all injected tumors and half of the contralateral tumors in murine models, indicating its potential as a powerful immunotherapy.

The mechanism of action involves both direct destruction of the injected tumors and the activation of a systemic CD8+ T cell response, which is crucial for clearing tumors, especially when combined with checkpoint blockade therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local Delivery of OncoVEXmGM-CSF Generates Systemic Antitumor Immune Responses Enhanced by Cytotoxic T-Lymphocyte-Associated Protein Blockade. Moesta, AK., Cooke, K., Piasecki, J., et al.[2021]

Talimogene laherparepvec (T-VEC) is the first FDA-approved oncolytic virus for treating metastatic melanoma, showing promise as a neoadjuvant therapy and in combination with ipilimumab, leading to significantly higher response rates than ipilimumab alone.

Ongoing research is exploring the use of T-VEC with PD-1 checkpoint inhibitors, and it is expected that oncolytic viruses like T-VEC will play a significant role in melanoma treatment, particularly for patients with accessible skin lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic Viruses for the Treatment of Metastatic Melanoma. Trager, MH., Geskin, LJ., Saenger, YM.[2021]

Talimogene laherparepvec (T-VEC) is the first oncolytic virus approved by the FDA for treating melanoma patients with injectable but non-resectable lesions, marking a significant advancement in cancer therapy.

Approved on October 27, 2015, T-VEC is commercialized as Imlygic® by Amgen, Inc., highlighting its potential as a novel treatment option for patients with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First oncolytic virus approved for melanoma immunotherapy. Pol, J., Kroemer, G., Galluzzi, L.[2021]

OncoVEXmGM-CSF, a modified herpes simplex virus, when used in combination with checkpoint inhibitors (anti-CTLA-4 or anti-PD-1), significantly enhanced tumor growth inhibition and reduced lung metastases in a murine melanoma model, indicating its potential to improve treatment outcomes for advanced melanoma.

The combination therapy not only induced strong T-cell responses specific to tumor antigens but also led to long-lasting immunity, as evidenced by cured mice being able to reject tumor rechallenges, suggesting a promising strategy to overcome resistance to existing checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OncoVEXmGM-CSFexpands tumor antigen-specific CD8+ T-cell response in preclinical models. Estrada, J., Zhan, J., Mitchell, P., et al.[2023]

In a phase II clinical trial involving 50 metastatic melanoma patients, the oncolytic herpes simplex virus Oncovex(GM-CSF) was shown to enhance local and systemic immune responses against tumors by increasing specific T cells that target melanoma antigens.

The treatment led to a significant reduction in regulatory T cells and suppressor T cells in injected lesions, suggesting that Oncovex(GM-CSF) not only stimulates an immune response but also helps to alleviate immune suppression within the tumor environment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local and distant immunity induced by intralesional vaccination with an oncolytic herpes virus encoding GM-CSF in patients with stage IIIc and IV melanoma. Kaufman, HL., Kim, DW., DeRaffele, G., et al.[2021]

In a phase II clinical trial with 50 patients, talimogene laherparepvec showed a significant response in injected lesions, with 67.2% of them decreasing in size by at least 30%, and 46.1% completely resolving.

The treatment also demonstrated systemic effects, with 47.8% of uninjected non-visceral lesions and 16.7% of visceral lesions showing a reduction in size, indicating that the therapy not only targets injected tumors but also stimulates an immune response against non-injected tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study. Kaufman, HL., Amatruda, T., Reid, T., et al.[2021]

Both JS-1 and T-VEC, a modified strain of HSV-1, effectively activate human cytotoxic T lymphocytes in response to melanoma cells, indicating a robust immune response against the cancer.

The study found no significant difference in immune activation between T-VEC and JS-1, suggesting that T-VEC's additional genetic modification (GM-CSF) does not enhance its immunostimulatory effects compared to the wild-type virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro Characterization of Enhanced Human Immune Responses by GM-CSF Encoding HSV-1-Induced Melanoma Cells. Delic, M., Boeswald, V., Goepfert, K., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12298472/

Advances in Oncolytic Viral Therapy in Melanoma VuSo is a genetically modified OV derived from a new strain of HSV-1 (RH018), which has a superior oncolytic activity determined by in vitro ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06216938

RP1 in Primary Melanoma to Reduce the Risk of Sentinel ... This early-phase study will examine Vusolimogene Oderparepvec, a genetically modified oncolytic viral strain of the herpes simplex type 1 (HSV-1) virus, ...

3. horizonscandb.pcori.org horizonscandb.pcori.org/report/topics/967

Vusolimogene oderparepvec (RP1) to treat anti–PD-1–failed ... VO is a modified, nonpathogenic herpes simplex virus type 1 (HSV-1) engineered to selectively replicate within tumor cells, causing their ...

4. 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.

5. ascopost.com ascopost.com/news/july-2025/rp1-plus-nivolumab-in-anti-pd-1-resistant-advanced-melanoma/

RP1 Plus Nivolumab in Anti-PD-1–Resistant Advanced ... “This result suggests that RP1 is effective in targeting cancer throughout the entire body and not just the injected tumor, which expands the ...

6. ir.replimune.com ir.replimune.com/news-releases/news-release-details/replimune-receives-complete-response-letter-fda-rp1-biologics

Replimune Receives Complete Response Letter from FDA ... We strongly believe that RP1 in combination with nivolumab can bring substantial benefit to advanced melanoma patients.” About RP1 RP1 ( ...