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

Trial Summary

What is the purpose of this trial?

This is a Phase 1b, single-center, open-label study, evaluating efficacy and safety of RP1 for the treatment of resectable cutaneous Squamous Cell Carcinoma in up to 12 evaluable patients. In this study, 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. The enrollment of patients with CSCC will determine study duration.

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.

What data supports the effectiveness of the treatment RP1, vusolimogene oderparepvec, for skin cancer?

Research on a similar treatment, talimogene laherparepvec (T-VEC), shows it can help treat advanced melanoma by directly killing cancer cells and boosting the immune system's response. T-VEC has been approved by the FDA for treating melanoma that cannot be surgically removed, suggesting potential effectiveness for similar treatments like RP1. ^{1 2 3 4 5}

How is the treatment RP1 (vusolimogene oderparepvec) for skin cancer different from other treatments?

RP1 (vusolimogene oderparepvec) is an oncolytic viral therapy, similar to talimogene laherparepvec (T-VEC), which works by directly destroying cancer cells and stimulating the immune system to attack tumors. This approach is unique compared to traditional treatments like chemotherapy or radiation, as it uses a virus to target cancer cells specifically. ^{3 4 6 7 8}

Research Team

Catherine VanHooft, HT

Principal Investigator

Rochester Dermatologic Surgery

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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, 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Observational study of talimogene laherparepvec use in the anti-PD-1 era for melanoma in the US (COSMUS-2). [2022]

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

Triple threat to cancer: rationale for combining oncolytic viruses, MEK inhibitors, and immune checkpoint blockade. [2021]

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

Talimogene Laherparepvec for the Treatment of Advanced Melanoma. [2021]

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

First Oncolytic Viral Therapy for Melanoma. [2017]

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

Clinical Challenges with Talimogene Laherparepvec: Cured Lymph Nodes Masquerading as Active Melanoma. [2020]

7. United States 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. [2021]

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

Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas. [2023]