RP1 for Advanced Skin Cancer in Transplant Patients

(ARTACUS Trial)

Recruiting at 17 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Replimune Inc.

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

Disqualifiers: Visceral metastases, Active herpetic infections, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests RP1, a modified virus, in organ transplant recipients with advanced skin cancer. RP1 works by killing cancer cells and boosting the immune system to fight the cancer. The HIV-1 accessory protein Vpr has been shown to induce cell cycle arrest and kill tumor cells by apoptosis.

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.

What data supports the effectiveness of the treatment RP1, Vusolimogene oderparepvec for advanced skin cancer in transplant patients?

Research on a similar treatment, Talimogene laherparepvec (T-VEC), shows it can help reduce skin cancer lesions in transplant patients by triggering immune responses without high risk of organ rejection. This suggests that RP1, which is related to T-VEC, might also be effective for advanced skin cancer in transplant patients. ^{1 2 3 4 5}

Is RP1 (Vusolimogene oderparepvec) safe for humans?

Talimogene laherparepvec (T-VEC), a similar treatment, has been used safely in patients with advanced melanoma and in organ transplant patients, showing mild side effects and no organ rejection. It suggests that RP1 may also be safe, but risks and benefits should be discussed with a healthcare team. ^{1 3 5 6 7}

What makes the drug RP1 (vusolimogene oderparepvec) unique for treating advanced skin cancer in transplant patients?

RP1 (vusolimogene oderparepvec) is unique because it is a genetically modified virus designed to selectively infect and kill cancer cells, while also stimulating the immune system to attack the tumor, which is different from traditional chemotherapy or targeted therapies that directly target cancer cell growth pathways. ^{8 9 10 11 12}

Research Team

May Cho, MD

Principal Investigator

Replimune Inc.

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Intra-tumoral Injection (Procedure)
• RP1 (Virus Therapy)

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.

Participant Groups

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

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

Who Is Running the Clinical Trial?

Replimune Inc.

Lead Sponsor

Trials

16

Recruited

1,700+

Findings from Research

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) 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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Use of Talimogene Laherparepvec to Treat Cutaneous Squamous Cell Carcinoma in a Renal Transplant Patient. [2023]

2. England 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. [2019]

3. New Zealand 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Safe and effective administration of T-VEC in a patient with heart transplantation and recurrent locally advanced melanoma. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

MEK inhibition enhances oncolytic virus immunotherapy through increased tumor cell killing and T cell activation. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

First Oncolytic Viral Therapy for Melanoma. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Talimogene laherparepvec (T-VEC) in advanced melanoma: complete response in a heart and kidney transplant patient. A case report. [2020]

8. United States 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. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Treatment of metastatic melanoma with pazopanib: A report of five patient cases. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Phase I Trial of Dabrafenib and Pazopanib in BRAF Mutated Advanced Malignancies. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Pazopanib treatment slows progression and stabilizes disease in patients with taxane-resistant cutaneous angiosarcoma. [2021]