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

NCT06216938 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: HCC 22-138
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Melanoma

Keywords

sentinel lymph node (SLN); herpes simplex virus 1 (HSV1); Granulocyte-macrophage colony stimulating factor (GM-CSF)

Outcome Measures

Primary Outcomes (1)

• Rate of Sentinel Lymph Node (SLN) Positivity

  Proportion of patients with sentinel lymph node lymph node positivity (disease present in lymph node per pathologic assessment).

  Up to 2 years (cohort)

Secondary Outcomes (7)

• Incidence of all treatment-emergent adverse events (TEAEs)

  Up to 2 years

• Incidence of ≥ Grade 3 Treatment Emergent Adverse Events (TEAEs)

  Up to 2 years

• Incidence of Serious Adverse Events (SAEs)

  Up to 2 years

• Incidence of fatal Adverse Events (AEs)

  Up to 2 years

• Incidence of all treatment-emergent adverse events (TEAEs) requiring withdrawal from RP1

  Up to 2 years

Study Arms (1)

Vusolimogene oderparepvec (RP1)

EXPERIMENTAL

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.

Biological: Vusolimogene oderparepvec (RP1)

Interventions

Vusolimogene oderparepvec (RP1) BIOLOGICAL

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.

Vusolimogene oderparepvec (RP1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Have a diagnosis of pT3b, T4a or T4b melanoma on biopsy. Patients must have grossly visible residual tumor, or a positive deep or lateral margin on initial biopsy. Patients with uveal melanoma are not eligible.
• Females of childbearing potential must have a negative beta-human chorionic gonadotropin (β-hCG) test with a minimum sensitivity of 25 IU/L or equivalent units of β-hCG during screening, before the first dose, and a negative urine pregnancy test on days of treatment (Day 1, 15 and 21). For serum and urine pregnancy tests and instructions (see Section 12.2).
• Female patients of reproductive potential must agree to avoid becoming pregnant and adhere to a highly effective contraception method until 90 days after last dose of RP1 alone. For a definition of highly effective contraceptive methods and instructions of patients and partners (see Section 12.2).
• Male patients of reproductive potential must agree to avoid impregnating a partner and adhere to a highly effective contraception method until 90 days after last dose of RP1 study agent and refrain from donating sperm during this period. For a definition of highly effective contraceptive methods and instructions of patients and partners (see Section 12.2).
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Demonstrate adequate organ function. All screening labs should be performed within 30 days of treatment initiation. Baseline labs may be used as screening labs.

You may not qualify if:

• Prior treatment with an oncolytic virus therapy.
• Has acute or chronic active hepatitis B and C virus infection or known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (HCV) (defined as HCV RNA \[qualitative\]) or HIV infection.
• Note: No testing for Hepatitis B, Hepatitis C, or HIV is required unless mandated by local health authority or clinically indicated.
• Had systemic infection requiring IV antibiotics or other serious infection within 14 days prior to dosing.
• Have active significant herpetic infections or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis).
• Conditions requiring treatment with immunosuppressive doses (\> 10 mg daily prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement therapy within 14 days after enrollment. For the definition of replacement therapy (Section 11.0 Supportive Care and Management of Adverse Reactions/Events).
• Major surgery ≤ 1 week prior to starting study drug. Note: Patients who undergo major surgery must adequately recover prior to starting study treatment.
• 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.
• History of documented allergic reactions or acute hypersensitivity reactions attributed to RP1 or any of its excipients.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacille Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed, however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Note: Available COVID-19 vaccines do not contain live virus.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that will be unfavorable for the administration of study drug or affect the explanation of drug toxicity or AEs or interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
• Has serious or uncontrolled medical disorders.
• Has known psychiatric, alcohol abuse, or substance abuse disorders that would interfere with cooperating with the requirements of the study.
• Is a person deprived of their liberty by a judicial or administrative decision, or an adult person subject to a legal protection measure.

Sponsors & Collaborators

• Yana Najjar: lead
• Replimune Inc.: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

MAPRE1 protein, human

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Yana Najjar, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Rose, RN, BSN

CONTACT

412-647-8587; kennaj@upmc.edu

Danielle Bednarz, RN, BSN

CONTACT

412-623-1191; bednarzdl@upmc.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine / Medical oncologist/hematologist

Study Record Dates

• First Submitted: January 11, 2024
• First Posted: January 22, 2024
• Study Start: March 7, 2024
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)