NCT06216938

RP1 in Primary Melanoma to Reduce the Risk of Sentinel Lymph Node Metastasis

Phase I Pilot Study of RP1 in Primary Melanoma to Reduce the Risk of Sentinel Lymph Node Metastasis

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: Yana Najjar · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

The majority of the almost 80,000 patients newly diagnosed with melanoma each year in the U.S. present with localized early-stage melanoma (i.e., clinical stage I/II). Per the standard of care (SOC), these patients are treated with a curative intent, including wide local excision (WLE), with additional sentinel lymph node (SLN) biopsy (SLNB) for patients with Breslow ≥ 0.8 mm or \< 0.8 mm with ulceration or a positive deep margin. The incidence of SLN metastases significantly increases with the Breslow thickness of the tumor and the presence of ulceration. For T3b (Breslow \> 2 mm, with ulceration), the incidence of SLN metastases is 23-42%. For T4b disease (Breslow \> 4 mm), this increases up to 63%. As the tumor draining lymph node (TDLN), the SLN is where naïve T cells are first primed. However, this is also the site where melanoma cells initiate tumor mediated immune suppression and form the pre-metastatic niche. Thus, the SLN is a key potential target for local immune therapeutic intervention in early-stage melanoma patients, whereby tumor-mediated immune suppression can be counteracted, and the antitumor immune response can be boosted. As SLN positivity is the single most important prognostic factor in early-stage melanoma, intervention at the SLN may prevent disease recurrence. Almost all patients diagnosed with melanoma will have already undergone a diagnostic biopsy by the time they are seen by medical oncology. The majority undergo shave biopsy by dermatology or their primary care physician, and a smaller proportion have undergone punch or excisional biopsy. Replimune is developing vusolimogene oderparepvec (RP1), an oncolytic immunotherapy. RP1 is a selectively replicating competent herpes simplex virus 1 (HSV-1) that expresses exogenous genes and is administered by intratumoral injection. Local delivery of RP1 following initial biopsy of primary melanoma, prior to SLNB, provides a unique setting to clinically assess the role of the TDLN in the biological efficacy of RP1.

Conditions

• Melanoma

Interventions

Type	Name	Description
BIOLOGICAL	Vusolimogene oderparepvec (RP1)	Vusolimogene Oderparepvec is a genetically modified oncolytic viral strain of the herpes simplex type 1 (HSV-1) virus, with potential oncolytic, immunostimulating and antineoplastic activities.

Timeline

• Start date: 2024-03-07
• Primary completion: 2028-03-31
• Completion: 2029-03-31
• First posted: 2024-01-22
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study