RP1 for Advanced Skin Cancer in Transplant Patients

(ARTACUS Trial)

Recruiting at 26 trial locations

Overseen By Clinical Trials at Replimune

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Replimune Inc.

Must not be taking: Anti-herpetics, CTLA-4-Ig

Disqualifiers: Visceral metastases, Active 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: Unknown

Duration: 52 weeks

65 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called RP1, an oncolytic virus injected directly into tumors, for its effects on advanced skin cancers in organ transplant patients. The main goals are to evaluate RP1's effectiveness in shrinking tumors and to ensure its safety. Ideal candidates for this trial include individuals who have undergone a solid organ or bone marrow transplant and are now facing advanced skin cancer unresponsive to treatments like surgery or radiation. Participants will be involved for about three years, including treatment and follow-up periods. As a Phase 1, Phase 2 trial, this research aims to understand how RP1 works in people and to measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking systemic anti-virals with anti-herpetic activity or CTLA-4-Ig medications, you may need to stop unless they are for organ allograft preservation.

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

Research has shown that RP1, when combined with the drug nivolumab, is safe for patients with advanced melanoma. In these studies, most side effects were mild to moderate, indicating they were generally not serious. Importantly, the FDA's review of RP1 with nivolumab found no new safety issues, suggesting that RP1 is well-tolerated in the studied settings.

This trial tests RP1 alone for advanced skin cancer in transplant patients. Although the safety data is based on RP1 used with another drug, the results are encouraging regarding its safety. Since this study is in its early stages, it is specifically designed to closely monitor safety and how well patients tolerate the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced skin cancer, which typically involve surgery, radiation, or chemotherapy, RP1 offers a unique approach as an oncolytic virus administered through intra-tumoral injection. Researchers are excited about RP1 because it not only directly attacks cancer cells but also stimulates the immune system to recognize and destroy them. This dual action could potentially lead to more effective and sustained responses in patients, especially those with compromised immune systems, such as transplant recipients.

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

Research has shown that RP1, a virus designed to attack and kill cancer cells, yields promising results in treating advanced skin cancers. In this trial, RP1 is administered as an intra-tumoral injection every two weeks. Studies indicate that RP1, especially when combined with the drug Opdivo®, leads to strong and lasting improvements in patients with melanoma and other skin cancers. Earlier trials demonstrated RP1's significant ability to fight tumors and its tolerability, even in patients with weakened immune systems. Additionally, early evidence suggests that RP1 might be more effective than T-VEC, the only virus currently approved for treating melanoma. These findings suggest that RP1 could be a powerful option for treating advanced skin cancers, including in transplant patients. ^{6 7 8 9 10}

Who Is on the Research Team?

May Cho, MD

Principal Investigator

Replimune Inc.

Are You a Good Fit for This Trial?

This trial is for organ transplant recipients with a life expectancy over 6 months, who have advanced skin cancers not treatable by surgery or radiation. Participants must have stable grafts, provide tumor samples, and have at least one measurable cancer lesion. They should be in good physical condition (ECOG ≤1) and not had certain infections or increased immunosuppression recently.

Inclusion Criteria

I agree to participate in the study and follow all its requirements.

Anticipated life expectancy > 6 months

Your initial heart test does not show signs of a recent heart problem.

Exclusion Criteria

I haven't needed more immunosuppressants in the last 2 months.

You currently have an active herpes infection or have had serious complications from a previous herpes infection.

I have not had an organ transplant rejection in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive RP1 via intra-tumoral injection every 2 weeks for up to 1 year

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Intra-tumoral Injection
• RP1

Trial Overview The study tests RP1, an oncolytic virus given through direct tumor injection to see how well it works (response rate) and its safety in up to 65 patients with skin cancers post-organ transplant. The trial includes screening, treatment for about a year, and two years of follow-up.

How Is the Trial Designed?

Group I: RP1, intra-tumoral injection, oncolytic virus Experimental Treatment 1 Intervention

RP1 administered as an intra-tumoral injection every 2 weeks.

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?

Replimune Inc.

Lead Sponsor

Trials

16

Recruited

1,700+

Published Research Related to This Trial

A 66-year-old female renal transplant patient with recurrent cutaneous squamous cell carcinoma (CSCC) showed significant improvement after treatment with Talimogene laherparepvec (T-VEC), which reduced the size of both treated and untreated lesions and decreased the rate of new lesions.

T-VEC appears to be a promising treatment option for transplant patients with CSCC, as it can elicit immune responses without the high risk of graft rejection associated with other therapies, such as anti-PD-1 treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Talimogene Laherparepvec to Treat Cutaneous Squamous Cell Carcinoma in a Renal Transplant Patient. Miller, M., Kim, NH., Thosani, MK., et al.[2023]

This case study presents the first instance of combining immune checkpoint blockade (ICB) with Talimogene laherparepvec (T-VEC) in a patient suffering from both primary cutaneous anaplastic large cell lymphoma (pcALCL) and metastatic melanoma, showcasing the complexities of treating patients with multiple cancers.

The patient experienced rapid progression of pcALCL while on nivolumab, an anti-PD-1 therapy, and developed a novel adverse effect, Kaposi's varicelliform eruption, after the first dose of T-VEC, indicating potential safety concerns when using this treatment in patients with concurrent malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kaposi's varicelliform eruption in a patient with metastatic melanoma and primary cutaneous anaplastic large cell lymphoma treated with talimogene laherparepvec and nivolumab. Miller, DM., Trowbridge, RM., Desai, A., et al.[2019]

Talimogene laherparepvec (T-VEC) was successfully administered to a patient with recurrent melanoma who had undergone heart transplantation, resulting in complete remission after 5 treatment cycles.

No signs of graft rejection were observed during the treatment, suggesting that T-VEC may be a safe immunotherapy option for organ transplant recipients, warranting further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe and effective administration of T-VEC in a patient with heart transplantation and recurrent locally advanced melanoma. Schvartsman, G., Perez, K., Flynn, JE., et al.[2023]

Talimogene laherparepvec (T-VEC) is the first oncolytic viral therapy approved for advanced melanoma, but its use has been limited due to competition from newer therapies and logistical challenges.

Recent studies suggest that T-VEC may be more effective when combined with immune checkpoint blockade, showing improved responses without added toxicity, indicating a potential for broader application in melanoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Update on the Role of Talimogene Laherparepvec (T-VEC) in the Treatment of Melanoma: Best Practices and Future Directions. Larocca, CA., LeBoeuf, NR., Silk, AW., et al.[2021]

Pazopanib effectively inhibits tumor growth and angiogenesis in breast cancer and melanoma cell lines with specific B-Raf mutations, particularly those with exon 11 mutations or HER2-activated wild type B-Raf.

However, pazopanib does not significantly inhibit tumors with the common V600E B-Raf mutation, indicating that the B-Raf genotype is a crucial factor in determining the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The B-Raf status of tumor cells may be a significant determinant of both antitumor and anti-angiogenic effects of pazopanib in xenograft tumor models. Gril, B., Palmieri, D., Qian, Y., et al.[2021]

The combination of dabrafenib and pazopanib was found to be safe, with no unexpected toxicities reported, although some patients experienced significant adverse events like bowel perforation and arthralgia.

Out of 23 patients with various BRAF-mutated tumors, 22% achieved a partial response, indicating potential efficacy of the combination therapy, particularly at higher dose levels where pazopanib levels were suboptimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Dabrafenib and Pazopanib in BRAF Mutated Advanced Malignancies. Haraldsdottir, S., Janku, F., Poi, M., et al.[2022]

In a study of five patients with taxane-resistant cutaneous angiosarcoma (cAS), pazopanib showed potential as a treatment option, with a median progression-free survival of 94 days and some patients experiencing partial responses or stable disease.

All patients expressed vascular endothelial growth factor receptor 2 (VEGFR-2), and those with higher expression levels had improved overall survival, suggesting that pazopanib may be more effective in patients with high VEGFR-2 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib treatment slows progression and stabilizes disease in patients with taxane-resistant cutaneous angiosarcoma. Ogata, D., Yanagisawa, H., Suzuki, K., et al.[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]

Pazopanib significantly improved progression-free survival (PFS) in patients with advanced renal cell carcinoma (RCC), with a median PFS of 9.2 months compared to 4.2 months for placebo, indicating its efficacy as a treatment option.

The objective response rate was notably higher with pazopanib at 30% versus only 3% for placebo, and the treatment was generally well-tolerated, with no major differences in quality of life reported between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial. Sternberg, CN., Davis, ID., Mardiak, J., et al.[2023]

Pazopanib, although primarily approved for advanced soft tissue sarcoma and renal cell carcinoma, was used in five cases to treat unresectable metastatic melanoma, indicating potential for off-label use in this challenging condition.

The study highlights a gap in treatment options for stage IV metastatic melanoma, as current guidelines are limited, suggesting a need for further research into the efficacy of pazopanib in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of metastatic melanoma with pazopanib: A report of five patient cases. Dayer, LE., Hutchins, LF., Johnson, JT.[2021]

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 (T-VEC) demonstrated a complete response in a 58-year-old man with melanoma who had a history of heart and kidney transplantation, suggesting its potential efficacy in patients with complex medical histories.

The patient tolerated T-VEC well, experiencing only mild side effects and no signs of organ transplant rejection, indicating that T-VEC may be a safe treatment option for organ transplant recipients with melanoma, although careful consideration of risks and benefits is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talimogene laherparepvec (T-VEC) in advanced melanoma: complete response in a heart and kidney transplant patient. A case report. Ressler, J., Silmbrod, R., Stepan, A., et al.[2020]

Citations

1. withpower.com withpower.com/trial/phase-1-carcinoma-4-2020-f9f37

RP1 for Advanced Skin Cancer in Transplant Patients This suggests that RP1, which is related to T-VEC, might also be effective for advanced skin cancer in transplant patients.

2. ir.replimune.com ir.replimune.com/news-releases/news-release-details/replimune-provides-new-clinical-data-broad-program-update-and

Replimune Provides New Clinical Data, Broad Program ... RP1 combined with Opdivo® (nivolumab) continues to demonstrate deep and durable responses in patients with melanoma and non-melanoma skin ...

3. 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 ...

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

RP1 and the Future of Oncolytic Therapy in Melanoma While T-VEC is the only approved oncolytic virus for melanoma, RP1 appears more potent in early data. 1. The IGNYTE trial (NCT03767348), a phase ...

5. primetherapeutics.com primetherapeutics.com/high-cost-therapy-profile-may-2025

High-Cost Therapy Profile: May 2025 Survival rates at 1-, 2- and 3-years were 75.3%, 63.3% and 54.8%, respectively. RP1 plus nivolumab was generally well tolerated. Most adverse ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9517

Efficacy and safety of RP1 combined with nivolumab in ... The updated data from this expanded cohort show that RP1 + nivo provides durable and clinically meaningful antitumor activity in pts with anti–PD-1–failed ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03867-5/fulltext

LBA46 Primary efficacy, safety, and survival data from the ... Conclusions. RP1 + nivo provided durable, clinically meaningful, antitumor activity with mostly grade 1–2 TRAEs in pts with advanced melanoma with confirmed PD ...

8. 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 ... ... (vusolimogene oderparepvec) in combination with nivolumab for the treatment of advanced melanoma. ... Importantly, no safety issues were raised.

9. targetedonc.com targetedonc.com/view/rp1-combination-shows-response-safety-in-advanced-melanoma

RP1 Combination Shows Response, Safety in Advanced ... Vusolimogene oderparepvec plus nivolumab showed responses and a favorable safety profile in advanced melanoma post-anti–PD-1 therapy, per phase 2 IGNYTE trial ...

10. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-01346

RP1 Combined With Nivolumab in Advanced Anti–PD-1– ... RP1 combined with nivolumab provided deep and durable systemic responses in patients with anti–PD-1–failed melanoma, including those with poor prognostic ...