MelanomaCutaneous Melanoma Resectable, MelanomaPhase 2NCT07862530
Neoadjuvant RP2 + Nivolumab in Patients With Melanoma
A Phase 2 study testing RP2 (vusolimogene oderparepvec), Nivolumab and Definitive Surgical Resection in people with MelanomaCutaneous Melanoma Resectable, Melanoma, run by Yana Najjar at 1 site in United States.
Trial summary
This is a Phase II study is being done to determine whether a new combination of therapies is safe and effective for adults to treat Melanoma before surgery. The two therapies that will be combined in this study are nivolumab and RP2. Nivolumab is a standard treatment for this type of cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MelanomaCutaneous Melanoma Resectable, Melanoma
- What is being tested?
- RP2 (vusolimogene oderparepvec), Nivolumab and Definitive Surgical Resection
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Dec 2026to 31 Dec 2033
- Phase
- Phase 2
- 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.
- Cytologically or histologically confirmed resectable stage IIIB, IIIC, IIID, or IV melanoma of cutaneous or unknown primary origin with one or more macroscopic lymph node metastases (clinically detectable), that can be biopsied and a maximum of 3 additional resectable in-transit metastases. A concurrent resectable primary melanoma is allowed. Clinical detectable lymph nodes are defined as either a palpable node ora non-palpable but enlarged lymph node according to RECISTv1.1 (at least 15 mm in short axis).
- Note: Patients with ocular melanoma are not eligible.
- Note: The determination of resectable disease is at the discretion of the principal investigator and surgeon.
- Note: Patients with BRAF V600E or V600K mutations are eligible.
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- At least one measurable lesion per RECIST v1.1; the injected lesion may also serve as the target lesion.
- Anti-PD-1 therapy naïve, or if previously treated with immunotherapy, recurrence occurred at least 12 weeks after the last dose of therapy.
- Females of childbearing potential must have a negative beta-human chorionic gonadotropin (β- hCG) test during screening, and a negative urine pregnancy test on days of treatment with RP2 and/or nivolumab. Female subjects are considered to be of childbearing potential unless one of the following criteria is met:
- Permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.
- Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception prior to study entry, during the course of the study, and for 90 days after the last dose of RP2 alone or 5 months after the last dose of nivolumab. An additional contraceptive method, such as a barrier method (e.g., condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods.
- 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 28 days of treatment initiation. Baseline labs may be used as screening -
Who cannot join
- Prior treatment with an oncolytic virus therapy.
- Active significant herpetic infections or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis).
- Immunodeficiency or use of systemic corticosteroids exceeding 10 mg of prednisone daily (or equivalent). Steroids for physiologic repletion (for example hydrocortisone for adrenal insufficiency) are permitted.
- Has acute or chronic active hepatitis B and C virus infection or known history of untreated 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 (see note).
- Note: No testing for Hepatitis B, Hepatitis C, or HIV is required unless mandated by local health authority or clinically indicated.
- Note: Participants with a history of HIV infection are considered eligible if CD4+ T cell counts are ≥ 350 cells/µL and the patient has had no opportunistic infections in the last 12 months.
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- Had systemic infection requiring IV antibiotics or other serious infection within 14 days prior to dosing.
- 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 RP2 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
- Will affect the explanation of drug toxicity or AEs
- Will interfere with the patient's participation for the full duration of the study
- In the opinion of the treating Investigator, deems participation not in the best interest of the patient
- Has serious or uncontrolled medical disorders that do not make it in the best interest of the patient to participate, in the opinion of the treating Investigator.
- Has known psychiatric, alcohol abuse, or substance abuse disorders that would in the opinion of the treating investigator 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.
- 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 areas should not be injected. Injection through an ulcerated area of a lesion should be avoided.
- Known additional malignancy that is progressing or requires active treatment (patients with definitively treated malignancies and low risk of recurrence, or patients with low risk of progression (such as indolent lymphomas) may be eligible after discussion with the PI).
- Active or untreated central nervous system (CNS) metastases.
- Active autoimmune disease requiring systemic therapy within the past 2 years, not including endocrinopathies or vitiligo.
- History of non-infectious pneumonitis or interstitial lung disease.
- Clinically significant hemoptysis or tumor-associated bleeding within 2 weeks prior to study treatment initiation.
- Clinically significant cardiovascular disease (i.e., including myocarditis or congestive heart failure (defined as New York Heart Association Functional Classification III or IV), or unstable angina, serious uncontrolled cardiac arrhythmia, cerebral vascular accident, or myocardial infarction within 6 months of treatment.).
- Use of anti-coagulation medication that cannot be held, at the discretion of the treating investigator, for the baseline biopsy and for surgical resection.
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
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Amy Rose, BSN, RN, 412-647-8587, kennaj@upmc.edu
Danielle Bednarz, BSN, RN, 412-623-1191, bednarzdl@upmc.edu
About this study
Official title: Phase II Trial of Neoadjuvant RP2 + Nivolumab in Patients With Resectable Melanoma
This is a Phase II study is being done to determine whether a new combination of therapies is safe and effective for adults to treat Melanoma before surgery. The two therapies that will be combined in this study are nivolumab and RP2.
Nivolumab is a standard treatment for this type of cancer. Nivolumab targets and blocks a receptor called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 may activate T-cells to find and kill cancer cells.
RP2 is a new treatment that is not yet FDA approved to treat this cancer. RP2 is a herpes simplex virus (a microscopic life form commonly known as the "cold sore virus") that has been changed in the laboratory to grow in and destroy cancer cells and to activate (turn on) the immune system to attack the cancer cells.
Read the detailed description
This single-arm Phase II study will evaluate the safety and efficacy of neoadjuvant RP2 in combination with nivolumab in adults with resectable advanced melanoma. Participants will receive RP2 and nivolumab prior to surgery, followed by adjuvant nivolumab after surgery. The study will assess pathologic response at surgery, treatment-related toxicity, tumor response, recurrence-free survival, and overall survival. Exploratory analyses will evaluate changes in immune and tumor biomarkers associated with treatment response.
- Being tested
- RP2 (vusolimogene oderparepvec), Nivolumab, Definitive Surgical Resection
- Keywords
- RP2; vusolimogene oderparepvec; nivolumab; neoadjuvant therapy; immunotherapy; oncolytic virus therapy; resectable cutaneous melanoma
- Medical subject headings
- Melanoma, Retinitis Pigmentosa 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RP2 (vusolimogene oderparepvec)Drug
RP2 (vusolimogene oderparepvec) RP2 will be injected directly into the tumor every 2 weeks for three doses before surgery.
NivolumabDrug
Nivolumab will be administered by intravenous infusion at a dose of 240 mg every 2 weeks for 3 doses during the neoadjuvant period, followed by 480 mg every 4 weeks for 11 doses during the adjuvant period.
Definitive Surgical ResectionProcedure or surgery
Participants will undergo definitive surgical resection of all clinically resectable melanoma lesions following completion of neoadjuvant treatment with RP2 and nivolumab. Surgery will be performed according to standard clinical practice and institutional guidelines. Resected tumor tissue and, where applicable, involved lymph nodes will be collected and evaluated for pathologic response and other study-related assessments.
| Study group | Role | What they receive |
|---|---|---|
| RP2 + Nivolumab | Experimental | RP2 + Nivolumab Followed by Surgery and Adjuvant Nivolumab Receives: Drug: RP2 (vusolimogene oderparepvec); Drug: Nivolumab; Procedure: Definitive Surgical Resection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Pathologic Response Rate (MPR)
Determine the rate of major pathologic response (MPR) following neoadjuvant combination therapy with RP2 and nivolumab in patients with resectable stage IIIB-IV cutaneous melanoma.
Measured: At the time of definitive surgery, approximately 8 to 10 weeks after initiation of neoadjuvant treatment.
Secondary outcomes (6)
Incidence of Dose-Limiting Toxicities
The proportion of participants who experience at least one dose-limiting toxicity during the protocol-defined DLT evaluation period. DLTs will be assessed according to the criteria specified in the protocol.
Measured: From the first dose through completion of the neoadjuvant treatment period, approximately 6 weeks.
Incidence of Treatment-Emergent Adverse Events
The number and percentage of participants who experience treatment-emergent adverse events, including Grade 3 or higher adverse events, serious adverse events, and adverse events leading to treatment discontinuation. Adverse events will be assessed using CTCAE version 5.0.
Measured: From the first dose of study treatment through 30 days after the last dose of study treatment.
Objective Response Rate (ORR)
Objective Response Rate (ORR): Percentage of patients achieving partial or complete response prior to surgery, per RECIST v1.1.
Measured: From baseline through the preoperative disease assessment, approximately 6 weeks after initiation of neoadjuvant treatment and before definitive surgery.
Recurrence-Free Survival (RFS)
Recurrence-free survival is defined as the time from definitive surgery to the first documented locoregional or distant disease recurrence or death from any cause, whichever occurs first. Participants who are alive and recurrence-free at the time of analysis will be censored at the date of their last disease assessment.
Measured: Time from treatment initiation to death from any cause, assessed up to 5 years
Overall Survival (OS)
Overall survival is defined as the time from initiation of study treatment to death from any cause. Participants who are alive at the time of analysis will be censored at the date they were last known to be alive.
Measured: Time from treatment initiation to death from any cause, assessed up to 5 years
Pathologic complete response (pCR)
Defined as the proportion of patients who show no detectable cancer (cells) in tissue samples after neoadjuvant treatment as assessed at the time of surgical resection.
Measured: At the time of definitive surgery, approximately 8 to 10 weeks after initiation of neoadjuvant treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2026
- Study start31 Dec 2026 (estimated)
- Primary completion27 Feb 2028 (estimated)
- Study completion31 Dec 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaCutaneous Melanoma Resectable, 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07862530
- Sponsor's protocol ID
- HCC 25-059
- Status last verified
- Sep 2026
- First submitted
- 29 Sep 2026
- Last updated
- 7 Oct 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 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Neoadjuvant RP2 + Nivolumab in Patients With Resectable Melanoma
- ClinicalTrials.gov ID
- NCT07862530
- Acronym / sponsor ID
- HCC 25-059
- Keywords
- RP2; vusolimogene oderparepvec; nivolumab; neoadjuvant therapy; immunotherapy; oncolytic virus therapy; resectable cutaneous melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Yana NajjarUniversity, hospital or other
- Collaborators
- Replimune, Inc.
- Study start
- 31 Dec 2026 (estimated)
- Primary completion
- 27 Feb 2028 (estimated)
- Study completion
- 31 Dec 2033 (estimated)
- First posted
- 7 Oct 2026 (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 is a Phase II study is being done to determine whether a new combination of therapies is safe and effective for adults to treat Melanoma before surgery. The two therapies that will be combined in this study are nivolumab and RP2.
Nivolumab is a standard treatment for this type of cancer. Nivolumab targets and blocks a receptor called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 may activate T-cells to find and kill cancer cells.
RP2 is a new treatment that is not yet FDA approved to treat this cancer. RP2 is a herpes simplex virus (a microscopic life form commonly known as the "cold sore virus") that has been changed in the laboratory to grow in and destroy cancer cells and to activate (turn on) the immune system to attack the cancer cells.
Detailed description
This single-arm Phase II study will evaluate the safety and efficacy of neoadjuvant RP2 in combination with nivolumab in adults with resectable advanced melanoma. Participants will receive RP2 and nivolumab prior to surgery, followed by adjuvant nivolumab after surgery. The study will assess pathologic response at surgery, treatment-related toxicity, tumor response, recurrence-free survival, and overall survival. Exploratory analyses will evaluate changes in immune and tumor biomarkers associated with treatment response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RP2 + Nivolumab | Experimental | Drug: RP2 (vusolimogene oderparepvec), Drug: Nivolumab, Procedure: Definitive Surgical ResectionRP2 + Nivolumab Followed by Surgery and Adjuvant Nivolumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Be willing and able to provide written informed consent for the trial.
- Be ≥ 18 years of age on day of signing informed consent.
- Cytologically or histologically confirmed resectable stage IIIB, IIIC, IIID, or IV melanoma of cutaneous or unknown primary origin with one or more macroscopic lymph node metastases (clinically detectable), that can be biopsied and a maximum of 3 additional resectable in-transit metastases. A concurrent resectable primary melanoma is allowed. Clinical detectable lymph nodes are defined as either a palpable node ora non-palpable but enlarged lymph node according to RECISTv1.1 (at least 15 mm in short axis).
- At least one measurable lesion per RECIST v1.1; the injected lesion may also serve as the target lesion.
- Anti-PD-1 therapy naïve, or if previously treated with immunotherapy, recurrence occurred at least 12 weeks after the last dose of therapy.
Key exclusion criteria (29 listed)
- Prior treatment with an oncolytic virus therapy.
- Active significant herpetic infections or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis).
- Immunodeficiency or use of systemic corticosteroids exceeding 10 mg of prednisone daily (or equivalent). Steroids for physiologic repletion (for example hydrocortisone for adrenal insufficiency) are permitted.
- Has acute or chronic active hepatitis B and C virus infection or known history of untreated 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 (see note).
- Had systemic infection requiring IV antibiotics or other serious infection within 14 days prior to dosing.
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 |
|---|---|---|
| RP2 (vusolimogene oderparepvec)RP2 (vusolimogene oderparepvec) RP2 will be injected directly into the tumor every 2 weeks for three doses before surgery. | Drug | RP2 + Nivolumab |
| NivolumabNivolumab will be administered by intravenous infusion at a dose of 240 mg every 2 weeks for 3 doses during the neoadjuvant period, followed by 480 mg every 4 weeks for 11 doses during the adjuvant period. | Drug | RP2 + Nivolumab |
| Definitive Surgical ResectionParticipants will undergo definitive surgical resection of all clinically resectable melanoma lesions following completion of neoadjuvant treatment with RP2 and nivolumab. Surgery will be performed according to standard clinical practice and institutional guidelines. Resected tumor tissue and, where applicable, involved lymph nodes will be collected and evaluated for pathologic response and other study-related assessments. | Procedure or surgery | RP2 + Nivolumab |
Primary outcome
Major Pathologic Response Rate (MPR)
Time frame: At the time of definitive surgery, approximately 8 to 10 weeks after initiation of neoadjuvant treatment.
Determine the rate of major pathologic response (MPR) following neoadjuvant combination therapy with RP2 and nivolumab in patients with resectable stage IIIB-IV cutaneous melanoma.
6 secondary outcomes
Incidence of Dose-Limiting Toxicities
Time frame: From the first dose through completion of the neoadjuvant treatment period, approximately 6 weeks.
Incidence of Treatment-Emergent Adverse Events
Time frame: From the first dose of study treatment through 30 days after the last dose of study treatment.
Objective Response Rate (ORR)
Time frame: From baseline through the preoperative disease assessment, approximately 6 weeks after initiation of neoadjuvant treatment and before definitive surgery.
Recurrence-Free Survival (RFS)
Time frame: Time from treatment initiation to death from any cause, assessed up to 5 years
Overall Survival (OS)
Time frame: Time from treatment initiation to death from any cause, assessed up to 5 years
Pathologic complete response (pCR)
Time frame: At the time of definitive surgery, approximately 8 to 10 weeks after initiation of neoadjuvant treatment.
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 7 Oct 2026.
- Individual participant dataSharing planned: No
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RP2 (vusolimogene oderparepvec), Nivolumab and Definitive Surgical Resection in people with MelanomaCutaneous Melanoma Resectable, 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 14 inclusion and 29 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: opening soon, as of the sponsor's last update on 7 Oct 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Pathologic Response Rate (MPR) (time frame: At the time of definitive surgery, approximately 8 to 10 weeks after initiation of neoadjuvant treatment.). 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 7 Oct 2026.