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

Trial Summary

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.

What data supports the effectiveness of the treatment Vusolimogene Oderparepvec (RP1) for melanoma?

Research on a similar treatment, Talimogene laherparepvec (T-VEC), which is also an oncolytic herpes virus encoding GM-CSF, shows it can effectively target melanoma cells, leading to tumor cell death and boosting the immune response. T-VEC has demonstrated promising results in clinical trials, improving response rates and showing potential when combined with other immune therapies. ^{1 2 3 4 5}

Is RP1 (Vusolimogene Oderparepvec) safe for humans?

The research does not provide specific safety data for RP1 (Vusolimogene Oderparepvec), but it discusses a similar treatment, talimogene laherparepvec, which is a modified herpes virus used for melanoma. This treatment has been approved by the FDA, suggesting it has been evaluated for safety in humans. ^{1 2 6 7 8}

What is the purpose of this trial?

This early-phase study will examine Vusolimogene Oderparepvec, a genetically modified oncolytic viral strain of the herpes simplex type 1 (HSV-1) virus, with potential oncolytic, immunostimulating and antineoplastic activities. Upon administration, vusolimogene oderparepvec specifically targets, infects and replicates in tumor cells and does not infect healthy cells. This results in tumor cell lysis and the release of virus particles which infect and replicate within nearby tumor cells, resulting in tumor cel death. The immune system is activated by the released tumor-associated antigens (TAAs) from the tumor cells creating an anti-tumor immune response against the tumor cells, thereby further killing the tumor cells. The virus itself also elicits a tumor-specific systemic immune and cytotoxic T-lymphocyte (CTL) response, thereby killing nearby non-infected tumor cells.

Research Team

Yana Najjar, MD

Principal Investigator

UPMC Hillman Cancer Center

Eligibility Criteria

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 haven't taken high doses of steroids, except for replacement therapy, in the last 14 days.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

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

Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

In vitro Characterization of Enhanced Human Immune Responses by GM-CSF Encoding HSV-1-Induced Melanoma Cells. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Talimogene laherparepvec (T-VEC) for the treatment of advanced melanoma. [2020]

4. United States 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. [2021]

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

Oncolytic Viruses for the Treatment of Metastatic Melanoma. [2021]

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

First oncolytic virus approved for melanoma immunotherapy. [2021]

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

Local Delivery of OncoVEXmGM-CSF Generates Systemic Antitumor Immune Responses Enhanced by Cytotoxic T-Lymphocyte-Associated Protein Blockade. [2021]

8. England pubmed.ncbi.nlm.nih.gov

OncoVEXmGM-CSFexpands tumor antigen-specific CD8+ T-cell response in preclinical models. [2023]