Oncolytic Virus for Melanoma: What the FDA Just Approved

An oncolytic virus for melanoma has now become part of clinical treatment in the United States. On August 6, 2026, the FDA granted accelerated approval to Tudriqev, a genetically engineered herpes simplex virus type 1, in combination with nivolumab for adults with unresectable advanced cutaneous melanoma that has progressed after PD-1-blocking therapy.

The idea sounds counterintuitive: a virus associated with infection is deliberately injected into a tumor. In this case, however, the virus has been engineered to attack tumor tissue while also making the cancer more visible to the immune system.

This matters because PD-1 inhibitors are among the most important treatments for advanced melanoma. They release a molecular “brake” on T cells and can produce long-lasting disease control. But some tumors never respond, while others eventually develop ways to escape immune attack.

Turning a tumor into an immune target

Tudriqev, known during development as RP1 or vusolimogene oderparepvec, is derived from HSV-1. After being injected directly into a tumor, it replicates within tumor cells and promotes their destruction.

Direct killing is only part of its design. RP1 carries a gene encoding GM-CSF, which can help recruit and activate immune cells, and another encoding the fusogenic viral protein GALV-GP-R−. This protein promotes fusion between neighboring cells, increasing tumor-cell destruction.

As cancer cells die, tumor antigens and inflammatory signals become more accessible to the immune system. In principle, a virus injected into one tumor can therefore help trigger an immune response against cancer cells elsewhere in the body. Nivolumab simultaneously blocks PD-1, helping T cells maintain their antitumor activity.

This combination of local tumor destruction and systemic immune activation is what makes oncolytic virotherapy biologically distinctive.

What IGNYTE found

The main clinical evidence came from IGNYTE, an open-label, multicenter study without a randomized control group. The registrational cohort included 140 adults with unresectable advanced melanoma whose disease had shown confirmed progression after at least eight weeks of prior anti-PD-1-based therapy.

RP1 was injected into accessible tumors every two weeks. Nivolumab was started with the second virus dose and could continue for up to two years.

In the published analysis of all 140 patients, the confirmed objective response rate was 32.9%. Fifteen percent achieved a complete response, meaning that all measurable signs of disease disappeared. Median duration of response was 33.7 months. Overall survival was 75.3% at one year and 63.3% at two years.

An important observation was that tumors that had not been injected also shrank, including visceral lesions. That pattern is consistent with a systemic immune effect, although the study design cannot establish precisely how much of that effect was caused by RP1 itself.

For the accelerated approval decision, the FDA used a narrower efficacy population of 91 patients who had at least one noninjected lesion. In this regulatory population, the objective response rate was 24.2%, with a median response duration of 14.1 months. An estimated 86.1% of responses lasted at least six months, and 54.6% lasted at least 12 months.

The different response numbers in the scientific paper and the FDA label therefore do not represent a contradiction: they come from different analysis populations and regulatory assessments.

The unanswered question

The central limitation of IGNYTE is its lack of a randomized control arm. Every patient received RP1 together with nivolumab. The trial therefore cannot cleanly separate the effect of the virus from the effect of renewed PD-1 blockade or from an interaction between the two.

This issue was central to the regulatory history. The FDA issued Complete Response Letters in 2025 and again in 2026, citing concerns that included heterogeneity in the study population, uncertainties in response assessment after intratumoral injections, and the inability of the trial to isolate RP1's contribution to the combination.

The eventual decision was an accelerated rather than traditional approval. It is based on objective response rate and duration of response, and continued approval requires confirmation of clinical benefit. The randomized phase III IGNYTE-3 trial is now comparing RP1 plus nivolumab with physician's-choice treatment.

The therapy also has risks specific to a live modified HSV-1 product. FDA labeling warns about accidental viral exposure, herpes infection or reactivation, complications related to tumor injection, and immune-mediated events. Common adverse reactions included fatigue, fever, infections, chills, musculoskeletal pain, nausea and injection-site reactions.

The approval therefore does not mean that a virus has been shown to “cure cancer.” It establishes something more specific: in a subset of patients with melanoma that had already progressed on one of the major forms of immunotherapy, an oncolytic virus combined with renewed PD-1 blockade can produce durable tumor responses. Whether RP1 itself is responsible for a substantial share of that benefit, and whether the strategy improves survival compared with other available treatments, still requires randomized evidence.