MelanomaEarly Phase 1NCT06216938
RP1 in Primary Melanoma to Reduce the Risk of Sentinel Lymph Node Metastasis
A Early Phase 1 study testing Vusolimogene oderparepvec (RP1) in people with Melanoma, run by Yana Najjar at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Vusolimogene oderparepvec (RP1)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Mar 2024to 31 Mar 2029
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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).
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- 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.
- Is a solid organ transplant recipient.
- Has a concurrent malignancy requiring active systemic therapy or ongoing radiation.
- Patients with tumors that are located near critical structures, such as the carotid artery or portal vein, or scalp lesions presenting with moderate to extensive bone erosion and tumors that may have invaded the heart, great vessels, or other critical structures will not be eligible because these area should not be injected. Injection through an ulcerated area of a lesion should be avoided.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Amy Rose, RN, BSN, 412-647-8587, kennaj@upmc.edu
Danielle Bednarz, RN, BSN, 412-623-1191, bednarzdl@upmc.edu
About this study
Official title: Phase I Pilot Study of RP1 in Primary Melanoma to Reduce the Risk of Sentinel Lymph Node Metastasis
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.
Read the 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
- Being tested
- Vusolimogene oderparepvec (RP1)
- Keywords
- sentinel lymph node (SLN), herpes simplex virus 1 (HSV1), Granulocyte-macrophage colony stimulating factor (GM-CSF)
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Vusolimogene oderparepvec (RP1) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 2 years (cohort)
Secondary outcomes (7)
Incidence of all treatment-emergent adverse events (TEAEs)
Distinct number of patients that experience treatment-emergent adverse events (TEAEs) by highest grade per CTCAE v5.0.
Measured: Up to 2 years
Incidence of ≥ Grade 3 Treatment Emergent Adverse Events (TEAEs)
Distinct number of patients that experience ≥ Grade 3 treatment-emergent adverse events (TEAEs) by highest grade per CTCAE v5.0.
Measured: Up to 2 years
Incidence of Serious Adverse Events (SAEs)
Distinct number of distinct patients that experience Serious Adverse Events (SAEs) by highest grade per CTCAE v5.0.
Measured: Up to 2 years
Incidence of fatal Adverse Events (AEs)
Distinct number of patients that experience fatal Adverse Events (AEs) by highest grade per CTCAE v5.0.
Measured: Up to 2 years
Incidence of all treatment-emergent adverse events (TEAEs) requiring withdrawal from RP1
Distinct number of patients that experience treatment-emergent adverse events (TEAEs) requiring withdrawal from RP1 by highest grade per CTCAE v5.0.
Measured: Up to 2 years
Recurrence Free Survival (RFS)
Median number of months from start of treatment to recurrence of disease or death from any cause. Recurrence of disease is defined as
Measured: Up to 3 years
Overall Survival (OS)
Median number of months from start of treatment until death from any cause.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2024
- Study start7 Mar 2024
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yana Najjar
- Sponsor type
- University, hospital or other
- Collaborators
- Replimune, Inc.
- Responsible party
- Sponsor-investigator, Yana Najjar, University of Pittsburgh
- Investigators
- Yana Najjar, MD, Principal investigator, UPMC Hillman Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06216938
- Sponsor's protocol ID
- HCC 22-138
- Status last verified
- Apr 2026
- First submitted
- 11 Jan 2024
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Pilot Study of RP1 in Primary Melanoma to Reduce the Risk of Sentinel Lymph Node Metastasis
- ClinicalTrials.gov ID
- NCT06216938
- Acronym / sponsor ID
- HCC 22-138
- Conditions
- Melanoma
- Keywords
- sentinel lymph node (SLN), herpes simplex virus 1 (HSV1), Granulocyte-macrophage colony stimulating factor (GM-CSF)
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Yana NajjarUniversity, hospital or other
- Collaborators
- Replimune, Inc.
- Study start
- 7 Mar 2024 (actual)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 Mar 2029 (estimated)
- First posted
- 22 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vusolimogene oderparepvec (RP1) | Experimental | Biological: Vusolimogene oderparepvec (RP1)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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).
Key exclusion criteria (18 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Biological | Vusolimogene oderparepvec (RP1) |
Primary outcome
Rate of Sentinel Lymph Node (SLN) Positivity
Time frame: Up to 2 years (cohort)
Proportion of patients with sentinel lymph node lymph node positivity (disease present in lymph node per pathologic assessment).
7 secondary outcomes
Incidence of all treatment-emergent adverse events (TEAEs)
Time frame: Up to 2 years
Incidence of ≥ Grade 3 Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to 2 years
Incidence of Serious Adverse Events (SAEs)
Time frame: Up to 2 years
Incidence of fatal Adverse Events (AEs)
Time frame: Up to 2 years
Incidence of all treatment-emergent adverse events (TEAEs) requiring withdrawal from RP1
Time frame: Up to 2 years
Recurrence Free Survival (RFS)
Time frame: Up to 3 years
Overall Survival (OS)
Time frame: Up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yana Najjar, MD principal investigator
UPMC Hillman Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Vusolimogene oderparepvec (RP1) in people with Melanoma, run by Yana Najjar at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amy Rose, RN, BSN (412-647-8587, kennaj@upmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Sentinel Lymph Node (SLN) Positivity (time frame: Up to 2 years (cohort)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.