Tudriqev

Tudriqev is used together with nivolumab to treat unresectable advanced melanoma of the skin (cutaneous melanoma) in adults whose cancer has grown or spread after treatment with a PD-1-blocking antibody medicine. "Unresectable" means the melanoma cannot be completely removed with surgery. Tudriqev is administered by a healthcare provider as an injection directly into tumors (intratumor injection). It is not injected into a vein.

Tudriqev (vusolimogene oderparepvec-wtpg), known during its development by Replimune as RP1, is a genetically modified oncolytic viral therapy. It is made from a modified herpes simplex virus type 1 (HSV-1) that has been changed in the laboratory so that it preferentially copies itself inside tumor cells. As the virus replicates, it breaks open (lyses) the cancer cells and releases signals that help the immune system recognize the tumor. Tudriqev also carries genes that make GALV-GP-R⁻ (a protein that increases direct tumor cell killing) and GM-CSF (a protein intended to help activate immune cells). When Tudriqev is combined with nivolumab in melanoma that no longer responds to anti-PD-1 therapy, the two medicines together may promote an anti-tumor immune response.

Tudriqev was approved by the FDA on August 6, 2026, under the accelerated approval designation. Continued approval for this use may depend on confirmation of benefit in further clinical trials.

Tudriqev is made from a live, modified herpes virus, so it can be passed to other people through accidental contact. Healthcare providers, caregivers, close contacts, pregnant women, and newborns should avoid direct contact with your injected tumors, dressings, or body fluids. Wash your hands well after touching the injection site or dressings, keep the injection sites covered as instructed, and dispose of used dressings and gloves as directed. If an accidental exposure happens, the affected area should be washed with soap and water, and the exposed person should contact their healthcare provider if signs of a herpes infection develop.

There is a risk of herpes infection or reactivation (such as cold sores or small blisters) after treatment. Tell your healthcare provider about any suspected herpes symptoms so they can be assessed and treated.

Because Tudriqev is injected into tumors, the procedure itself can cause complications, including bleeding, infection, and injury to internal organs (for example, a collapsed lung, called pneumothorax, when tumors near the lung are treated).

When used with nivolumab, Tudriqev can cause immune-mediated events, where the immune system attacks healthy parts of the body. Reported events have included inflammation of the colon, liver, heart muscle, and nerves, as well as capillary leak syndrome, skin reactions, and vitiligo.

Before receiving Tudriqev, tell your healthcare provider about all of your medical conditions, including if you:

• have a history of herpes infection, since Tudriqev can cause a herpes infection or reactivate an existing one
• have any condition or take any medicine that weakens your immune system, or you have close contact with people who are pregnant, are newborns, or have weakened immune systems, because Tudriqev can be passed to others
• are pregnant or plan to become pregnant. There are no data on the use of Tudriqev in pregnant women, so its safety during pregnancy is not known. If you can become pregnant, your provider will check your pregnancy status before you start
• are breastfeeding or plan to breastfeed. It is not known whether Tudriqev passes into human milk or its effects on a breastfed baby. You should not breastfeed during treatment and for 90 days after your final dose.

The safety and effectiveness of Tudriqev have not been established in children.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Also tell them about any antiviral medicines, because these can affect how well Tudriqev works (see What should I avoid).

Females and males of reproductive potential

Females who can become pregnant should use effective birth control during treatment with Tudriqev and for 90 days after the last dose.

Males with a female partner who can become pregnant should also use effective birth control and should not donate sperm during treatment and for 90 days after the last dose.

Serious side effects

Tudriqev may cause serious side effects, including:

• Spread of the virus to other people (transmission). Tudriqev can be passed to close contacts through accidental exposure to injected tumors, dressings, or body fluids, which may cause a herpes infection.
• Herpes infection or reactivation. Tudriqev may cause a new herpes infection or reactivate an existing one. Tell your healthcare provider about symptoms such as small bumps that turn into blisters or sores.
• Injection procedure complications. The injection procedure has caused bleeding, infection, and, when internal tumors are treated, injury to organs such as a collapsed lung (pneumothorax). Your healthcare provider will monitor you during and after treatment.
• Immune-mediated events (with nivolumab). Tudriqev used with nivolumab may cause the immune system to attack healthy tissue. Reported events include inflammation of the colon (colitis), liver (hepatitis), heart (myocarditis), and nerves (neuropathy), as well as capillary leak syndrome, dermatitis, and vitiligo.

Common side effects

The most common side effects of Tudriqev (used with nivolumab), are:

• tiredness (fatigue)
• fever
• infections
• chills
• muscle and bone pain
• nausea
• diarrhea
• injection site reaction
• headache
• cough
• flu-like illness
• rash
• vomiting
• itching
• joint pain
• constipation
• reduced appetite
• dizziness
• shortness of breath
• bleeding
• swelling (edema)
• stomach (abdominal) pain.

Common changes in laboratory tests include low red blood cells (anemia), a lower lymphocyte count, and changes in salts and minerals such as sodium, phosphate, and potassium, as well as increases in liver enzymes and in the pancreatic enzymes lipase and amylase.

Tell your healthcare provider about any side effects that bother you or that do not go away. These are not all the possible side effects of Tudriqev. Call your doctor for medical advice about side effects. To report suspected side effects, contact Replimune, Inc. at 1-877-375-0095 or [email protected], or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

The effectiveness of Tudriqev with nivolumab was studied in IGNYTE (NCT03767348), an open-label, multicenter Phase 1/2 study. Adults with advanced cutaneous melanoma whose cancer had grown while they were being treated with an anti-PD-1 medicine made up a registrational group within the study. In this group, 140 people received Tudriqev plus nivolumab, and effectiveness was measured in the 91 who had at least one tumor that was not injected. Most had stage IV (metastatic) disease, about half had melanoma that was PD-L1 negative, and many had tumors in the lung or liver.

The main measures were how many people had their tumors shrink (objective response rate, or ORR) and how long those responses lasted (duration of response, or DoR). In these patients, 24.2% (about 1 in 4) had a tumor response. Among those who responded, the median length of response was 14.1 months. About 86% of responders still had a response at 6 months, and about 55% still had a response at 12 months. The IGNYTE results were published in the Journal of Clinical Oncology.

Because Tudriqev was approved under accelerated approval based on these measures, a confirmatory Phase 3 study called IGNYTE-3 (NCT06264180) is underway to confirm its benefit. Continued approval for this use may depend on the results.

• Tudriqev is given by a healthcare provider who is experienced in cancer treatment. You do not inject it yourself.
• Tudriqev is injected directly into one or more tumors. It is not given into a vein.
• The recommended dose is 1 mL for each centimeter of the largest dimension of the tumor, up to a maximum of 10 mL across all tumors treated at each visit.
• Tudriqev is given every 2 weeks for 8 doses in a row. The first dose uses a lower-strength (1 million PFU/mL) suspension, and the later doses use a higher-strength (10 million PFU/mL) suspension.
• Nivolumab is given as an intravenous (into a vein) infusion starting at Week 3, following its own prescribing information.
• Your provider will decide which tumors to treat and how to inject them (into skin tumors or, using imaging for guidance, into deeper tumors in organs such as the liver or lung).
• After each injection, the site is covered with a dressing. Keep the injection sites covered for at least 48 hours and follow your provider's instructions for changing dressings safely.

Avoid direct, unprotected contact between your injected tumors, dressings, or body fluids and other people, especially people who are pregnant, newborns, and people with weakened immune systems, to lower the risk of passing the virus to them.

Antiviral medicines (medicines used to treat herpes and other viral infections) may make Tudriqev less effective. If you need systemic antiviral treatment for a herpes infection, Tudriqev treatment should be delayed until 72 hours after you finish the antiviral therapy. Tell your healthcare provider before starting any antiviral medicine.

Antiviral medicines may reduce how well Tudriqev works. Tell your healthcare provider and pharmacist about all the medicines you take, and keep an up-to-date list to show them. Do not start a new medicine without checking with your provider.

Active ingredient: vusolimogene oderparepvec-wtpg (a modified herpes simplex virus type 1 that carries the genes for GALV-GP-R⁻ and GM-CSF; the HSV-1 genes ICP34.5 and ICP47 have been removed).

Inactive ingredients: disodium hydrogen phosphate dihydrate, sodium dihydrogen phosphate dihydrate, sodium chloride, myo-inositol, d-sorbitol, and recombinant human serum albumin, with water for injection.