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News|Articles|August 6, 2026

FDA Grants Accelerated Approval to RP1 Plus Nivolumab for Advanced Melanoma After Anti–PD-1 Therapy

Author(s)Chris Ryan
Fact checked by: Kyle Doherty
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Key Takeaways

  • Accelerated approval covers RP1 plus nivolumab for unresectable advanced cutaneous melanoma with progression on prior PD-1–blocking antibody–based therapy.
  • Regulatory trajectory included two complete response letters before a third BLA acceptance in June 2026.
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The FDA granted accelerated approval to RP1 plus nivolumab in anti–PD-1 therapy–pretreated advanced melanoma.

The FDA has granted accelerated approval to vusolimogene oderparepvec-wtpg (Tudriqev; RP1) in combination with nivolumab (Opdivo) for the treatment of adult patients with unresectable advanced cutaneous melanoma who experienced disease progression on a PD-1–blocking antibody–based regimen.1

The approval followed a lengthy regulatory history for the combination. After receiving a pair of complete response letters to the first two submitted biologics license applications, the FDA accepted a third in June 2026.2 This was followed by a positive opinion from the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC), which voted 10 to 3 that the efficacy results from the phase 1/2 IGNYTE trial (NCT03767348) were evaluable and clinically meaningful for the combination in this setting.3

Findings from IGNYTE that supported the approval showed that patients in the efficacy-evaluable population (n = 91) achieved an objective response rate (ORR) of 24.2% (95% CI, 15.8%-34.3%).1 The median duration of response (DOR) was 14.1 months (95% CI, 10.7-not reached).

How was IGNYTE conducted?

The single-arm, multicohort trial included a registrational phase 2 melanoma cohort, where investigators enrolled 140 patients with advanced melanoma whose disease progressed following a prior anti–PD-1–containing regimen.4 Patients needed to receive at least 8 weeks of anti–PD-1 therapy, either as monotherapy or in combination with anti–CTLA-4 therapy, as their most recent prior treatment. At least 1 measurable lesion per RECIST 1.1 criteria and injectable lesions comprising at least 1 cm in longest diameter were also required.

RP1 was initated with an intratumoral dose, followed by up to 7 additional doses every 2 weeks. Patients also received nivolumab at 240 mg starting with the second dose of RP1, and it was given every 2 weeks for up to 8 cycles, then continued at 480 mg every 4 weeks for up to an additional 21 cycles.

ORR per modified RECIST 1.1 criteria by blinded independent central review (BICR) served as the primary end point in the registration-intended cohort.

What safety and dosing information should be known about RP1 plus nivolumab?

Among safety-evaluable patients treated with RP1 plus nivolumab during IGNYTE (n = 140), the most common non-laboratory adverse effects reported in at least 10% of patients included fatigue, pyrexia, infections, chills, musculoskeletal pain, nausea, diarrhea, injection site reaction, headache, cough, influenza like illness, rash, vomiting, pruritus, arthralgia, constipation, decreased appetite, dizziness, dyspnea, hemorrhage, edema, and abdominal pain.1

RP1 is recommended at a dose of 1 mL/cm of the largest dimension of the tumor, up to a maximum of 10 mL across all treated lesions per dose. Size of injectable lesions should be measured prior to each RP1 dose to determine the necessary dose. RP1 is recommended every 2 weeks for 8 consecutive doses, with the first dose concentrated at 10⁶ plaque-forming units (PFU)/mL, followed by 10⁷ PFU/mL for subsequent doses. For patients with multiple tumors, the FDA recommended prioritizing tumors growing the fastest and the largest new/exisiting lesions that are suitable for injection. Initiation of nivolumab is recommended at week 3.

References

  1. FDA grants accelerated approval to vusolimogene oderparepvec-wtpg in combination with nivolumab for melanoma. FDA. August 6, 2026. Accessed August 6, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-vusolimogene-oderparepvec-wtpg-combination-nivolumab-melanoma
  2. FDA advisory committee to weigh RP1 plus Nnvolumab in anti–PD-1–pretreated advanced melanoma. OncLive. July 29, 2026. Accessed August 6, 2026. https://www.onclive.com/view/fda-advisory-committee-to-weigh-rp1-plus-nivolumab-in-anti-pd-1-pretreated-advanced-melanoma
  3. FDA CTGTAC votes in favor of RP1/nivolumab data in advanced melanoma. OncLive. July 30, 2026. Accessed August 6, 2026. https://www.onclive.com/view/fda-ctgtac-ignyte-data-rp1-nivolumab-advanced-melanoma
  4. Wong MK, Milhem MM, Sacco JJ, et al. RP1 combined with nivolumab in advanced anti–PD-1–failed melanoma (IGNYTE). J Clin Oncol. 2025;43(33):3589-3599. doi:10.1200/JCO-25-01346

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