Last updated: August 14, 2026
RP1 (Tudriqev, vusolimogene oderparepvec, vusolimogene oderparepvec-wtpg) is a first-in-class oncolytic immunotherapy developed by Replimune on the RPx platform. It received FDA accelerated approval on August 2, 2026, in combination with nivolumab (an anti-PD-1 antibody), for adults with unresectable advanced cutaneous melanoma that has progressed on a prior anti-PD-1-containing regimen — the first oncolytic immunotherapy approved in combination with anti-PD-1 for advanced melanoma, and a new option in the difficult checkpoint-refractory setting.
Mechanism of action:RP1 is a genetically modified oncolytic strain of herpes simplex virus type 1 (HSV-1) engineered to selectively infect and replicate in tumor cells (not healthy cells), and armed with a fusogenic glycoprotein (GALV-GP R-) and GM-CSF. Given by intratumoral injection, it kills injected tumor cells directly (oncolysis), releases tumor-associated antigens, and triggers a systemic anti-tumor immune response against both the injected tumor and distant (non-injected) deposits — turning the injected lesion into an in-situ vaccine. Combining RP1 with nivolumab is intended to release the PD-1 “brake” on the T-cell response the virus provokes.
Regulatory status:FDA accelerated approval (August 2, 2026) in 1 indication: with nivolumab, for unresectable advanced cutaneous melanoma that progressed on prior anti-PD-1 therapy. Based on objective response rate and duration of response from the Phase 1/2 IGNYTE trial (objective response rate ~33.6%, median duration of response ~24.8 months). Continued approval is contingent on verification of clinical benefit in the confirmatory Phase 3 IGNYTE-3 trial (NCT06264180).
For advanced melanoma, checkpoint immunotherapy (anti-PD-1 drugs such as pembrolizumab and nivolumab, alone or with anti-CTLA-4) transformed survival over the last decade. But roughly half of patients still progress on or after these drugs, and once melanoma becomes anti-PD-1-refractory, the options narrow — the disease has already outmaneuvered the most powerful class of melanoma immunotherapy. This is the population RP1 is approved for.
RP1 attacks the problem from a different angle. Instead of a systemic drug that circulates through the body, RP1 is injected directly into a tumor, where the engineered herpes virus replicates and bursts the cancer cells. The debris released — tumor antigens plus danger signals from the dying, virus-infected cells — acts like a personalized vaccine made from the patient's own tumor, waking up T cells that can then travel and attack melanoma elsewhere in the body (including tumors that were never injected). Pairing this with nivolumab takes the brakes off those newly-activated T cells. In the Phase 1/2 IGNYTE trial, RP1 plus nivolumab produced responses in about a third of patients (~33.6% objective response rate) who had already progressed on anti-PD-1, and the responses tended to be durable (median duration of response ~24.8 months) — the basis for the August 2, 2026 accelerated approval.
An oncolytic-immunotherapy lineage. RP1 is not the first oncolytic immunotherapy in melanoma — that was talimogene laherparepvec (T-VEC, Imlygic), approved in 2015 as a single-agent local therapy for surgically-recurrent melanoma. RP1 is a next-generation HSV-1 (additionally armed with a fusogenic glycoprotein to increase tumor-cell killing) and is approved specifically in combination with anti-PD-1 for the harder, checkpoint-refractory advanced setting. Because it works by injection into an accessible tumor and does not require a genetic biomarker, it broadens who can be considered for an immune-based option after checkpoint failure.
RP1 (Tudriqev) has 1 active FDA approval — an accelerated approval granted August 2, 2026.
Unresectable or Metastatic Melanoma, Post Anti-PD-1 — RP1 + Nivolumab (accelerated approval)
★ Accelerated Approval — What It Means for Patients
RP1 was approved through the FDA's accelerated approval pathway, which lets a drug reach patients based on a measure that is reasonably likely to predict clinical benefit — here, objective response rate and duration of response from the single-arm Phase 1/2 IGNYTE trial — rather than waiting for a completed randomized survival trial. This is common for drugs addressing a serious disease with unmet need, which post-anti-PD-1 melanoma is.
The trade-off: continued approval is contingent on a confirmatory trial verifying clinical benefit. For RP1 that trial is the randomized Phase 3 IGNYTE-3 (NCT06264180), still recruiting. Practically, this means RP1 + nivolumab is available now for eligible patients, and the Phase 3 will determine whether the approval becomes full. RP1 reached approval on its third BLA review cycle after two prior complete response letters (2025 and April 2026).
The recruiting vusolimogene oderparepvec interventional trials in the ClinTrialFinder corpus as of August 8, 2026. Both are in melanoma. (Trials are grouped by phase.)
Beyond these two, other vusolimogene oderparepvec studies exist but are not currently enrolling: a terminated Phase 1/2 combination in triple-negative breast cancer (neoBREASTIM, NCT06067061), an active-but-not-recruiting Phase 2 in angiosarcoma (NCT06898970), and a closed melanoma expanded-access program (NCT06590480). For the latest list: view all recruiting vusolimogene trials on ClinicalTrials.gov.
Platform: RP1 is built on Replimune's RPx platform, a proprietary oncolytic herpes simplex virus type 1 (HSV-1) backbone. The virus is genetically modified to replicate selectively in tumor cells and is armed with two payloads: a fusogenic glycoprotein, GALV-GP R- (which causes infected tumor cells to fuse and die in a highly immunogenic way), and GM-CSF (which recruits and matures antigen-presenting cells to strengthen the immune response). Unlike a biomarker-targeted drug, RP1 does not require a specific mutation or HLA type — it requires an injectable tumor.
How it works, step by step: (1) RP1 is injected directly into a tumor (skin, subcutaneous, nodal, or an accessible deeper lesion, sometimes under image guidance). (2) The virus infects and replicates inside the tumor cells, which are permissive to HSV-1 replication in ways healthy cells are not. (3) Infected tumor cells undergo immunogenic cell death — they burst (oncolysis) and, via the fusogenic GALV-GP, fuse with neighbors — releasing tumor-associated antigens plus viral “danger” signals. (4) GM-CSF and those danger signals recruit and activate antigen-presenting cells, which carry the tumor antigens to lymph nodes and prime tumor-specific T cells. (5) Those T cells circulate and can attack melanoma throughout the body — including tumors that were never injected (a systemic, sometimes “abscopal,” effect). (6) Adding nivolumab blocks PD-1, releasing the checkpoint brake on the T-cell response the virus provokes — the rationale for the approved combination in checkpoint-experienced patients.
Where RP1 sits in the oncolytic lineage: The first oncolytic immunotherapy approved in melanoma was talimogene laherparepvec (T-VEC / Imlygic) in 2015 — an HSV-1 armed with GM-CSF, approved as a single agent for local treatment of surgically-recurrent cutaneous, subcutaneous, and nodal melanoma. RP1 extends the concept with a next-generation backbone (adding the fusogenic GALV-GP payload) and an approval in combination with anti-PD-1 for advanced, checkpoint-refractory disease. ClinTrialFinder does not currently have a dedicated oncolytic-immunotherapy mechanism hub.
Unlike many modern melanoma drugs, RP1 does not require a genetic biomarker (no BRAF mutation test, no HLA typing). Its eligibility rests on two practical criteria:
A note on the confirmatory trial's stricter criteria. The approved indication is post–anti-PD-1. The confirmatory Phase 3 IGNYTE-3 (NCT06264180) enrolls a more heavily pretreated group — melanoma that progressed on both anti-PD-1 and anti-CTLA-4 (or patients not eligible for anti-CTLA-4). If you are exploring the trial rather than commercial therapy, confirm which criteria apply. Standard herpesvirus handling precautions also apply to oncolytic HSV-1 therapy, and caution is warranted in patients who are significantly immunosuppressed or in close contact with immunosuppressed or pregnant individuals — discuss with the treating team.
See the Melanoma trials page for the broader melanoma trial landscape (including checkpoint, targeted, cell therapy, and other options).
RP1 + nivolumab is a new option specifically for melanoma that has progressed on anti-PD-1. Several other approaches are used in this setting — some complementary, some alternatives.
RP1's own toxicity, as an intratumorally-injected oncolytic virus, tends to be dominated by low-grade constitutional and injection-related effects: fever, chills, fatigue, and flu-like symptoms (reflecting the immune activation the virus is designed to cause), plus injection-site reactions (pain, swelling). These are generally manageable and are an expected consequence of the mechanism.
Because RP1 is approved in combination with nivolumab, patients are also exposed to the immune-related adverse events (irAEs) that come with anti-PD-1 therapy — immune inflammation that can affect the skin, colon (colitis/diarrhea), liver (hepatitis), endocrine glands (thyroid, adrenal, pituitary), lungs (pneumonitis), and, less commonly, other organs. These require prompt recognition and, when significant, corticosteroids and treatment holds; the melanoma care team monitors for them throughout treatment.
Herpesvirus precautions. As an oncolytic HSV-1 product, RP1 carries standard handling and contact precautions, and caution applies for patients who are significantly immunosuppressed or in close contact with immunosuppressed or pregnant individuals. Herpetic symptoms (for example, cold-sore-like lesions) can occur and are treatable with standard anti-herpes medication.
This section summarizes the general profile of the drug class and the RP1 + nivolumab combination; it is not a substitute for the FDA-approved prescribing information. Verify the current Tudriqev label and discuss the specific risks and monitoring plan with the treating oncology team.
What is RP1 (Tudriqev / vusolimogene oderparepvec)?
RP1 (brand name Tudriqev, generic vusolimogene oderparepvec / vusolimogene oderparepvec-wtpg) is a first-in-class oncolytic immunotherapy from Replimune, built on the RPx platform. It is a genetically modified oncolytic herpes simplex virus type 1 (HSV-1) engineered to replicate selectively in tumor cells and armed with a fusogenic glycoprotein (GALV-GP R-) and GM-CSF. Given by intratumoral injection, it bursts injected tumor cells (oncolysis) and provokes a systemic anti-tumor immune response against injected and non-injected tumors alike. On August 2, 2026 the FDA granted accelerated approval to RP1 in combination with nivolumab for adults with unresectable advanced cutaneous melanoma that progressed on a prior anti-PD-1 regimen, based on objective response rate and duration of response from the Phase 1/2 IGNYTE trial (~33.6% objective response rate, ~24.8 months median duration of response). It is the first oncolytic immunotherapy approved in combination with anti-PD-1 for advanced melanoma.
Which patients qualify for RP1?
RP1 (Tudriqev) is FDA-approved, in combination with nivolumab, for adults with unresectable advanced cutaneous melanoma that has progressed on a prior anti-PD-1-containing regimen (for example, after pembrolizumab or nivolumab). Two practical points: (1) prior anti-PD-1 progression defines the approved setting — the checkpoint-refractory population where options have been limited; and (2) an injectable tumor is needed, because RP1 is given by intratumoral injection (skin, subcutaneous, nodal, or an accessible deeper lesion, sometimes with image guidance). RP1 does not require a genetic biomarker (no BRAF test, no HLA typing). Note that the confirmatory Phase 3 trial IGNYTE-3 (NCT06264180) enrolls a more pretreated group (post anti-PD-1 and anti-CTLA-4). Always confirm current eligibility and the injectable-lesion requirement with the treating oncologist and the label or trial.
How does RP1 differ from T-VEC (talimogene laherparepvec, Imlygic)?
Both are intratumoral oncolytic immunotherapies based on modified HSV-1, but they differ in engineering, combination, and setting. T-VEC (Imlygic, approved 2015) was the first oncolytic immunotherapy approved for melanoma — an HSV-1 armed with GM-CSF, used as a single agent for local treatment of unresectable cutaneous, subcutaneous, and nodal melanoma lesions recurrent after surgery. RP1 uses Replimune's next-generation RPx backbone with an added fusogenic glycoprotein (GALV-GP R-) to increase immunogenic tumor-cell killing, and its 2026 accelerated approval is specifically in combination with nivolumab for advanced melanoma that progressed on prior anti-PD-1. In short: T-VEC is a single-agent local therapy for surgically-recurrent melanoma; RP1 + nivolumab is a combination for checkpoint-refractory advanced melanoma. Both turn an injected tumor into an in-situ vaccine.
What are the main side effects of RP1?
As an intratumorally-injected oncolytic virus, RP1's own toxicity is dominated by low-grade constitutional and injection-related effects: fever, chills, fatigue, flu-like symptoms, and injection-site reactions (pain, swelling). Because it is approved with nivolumab, patients are also exposed to immune-related adverse events of anti-PD-1 therapy — inflammation that can affect the skin, colon (colitis), liver (hepatitis), endocrine glands (thyroid, adrenal, pituitary), lungs (pneumonitis), and other organs — which require monitoring and, when significant, corticosteroids and treatment holds. Standard herpesvirus handling and contact precautions apply, with caution in significantly immunosuppressed patients or those in contact with immunosuppressed or pregnant individuals. This is a general class summary, not a substitute for the FDA label — verify the current Tudriqev prescribing information and discuss with your oncology team. See the Melanoma trials page for the broader landscape.
Is RP1 being studied in cancers other than melanoma?
The RP1 platform has been explored beyond melanoma, but the recruiting vusolimogene oderparepvec trials in the ClinTrialFinder corpus are currently both in melanoma: the confirmatory Phase 3 IGNYTE-3 (NCT06264180) in advanced melanoma post-checkpoint, and a neoadjuvant Phase 1 in primary melanoma (NCT06216938). Other vusolimogene studies exist but are not currently enrolling — a terminated Phase 1/2 in triple-negative breast cancer (neoBREASTIM, NCT06067061), an active-but-not-recruiting Phase 2 in angiosarcoma (NCT06898970), and a closed melanoma expanded-access program (NCT06590480). So the oncolytic concept is being tested more broadly, but RP1's currently-approved and currently-recruiting footprint is a melanoma story. Trial status changes frequently — use the search below or check ClinicalTrials.gov for the latest.
Find RP1 and Melanoma Immunotherapy Trials Matched to Your Situation
Use ClinTrialFinder's AI-powered matching to find RP1 (Tudriqev) and other melanoma trials based on your specific situation — melanoma type and stage, prior anti-PD-1 or anti-CTLA-4 therapy, BRAF status, injectable disease, and country.
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