On August 6, the U.S. Food and Drug Administration (FDA) granted accelerated approval to vusolimogene oderparepvec-wtpg (Tudriqev), a genetically modified oncolytic viral therapy, in combination with nivolumab for the treatment of adult patients with unresectable advanced cutaneous melanoma who experienced disease progression on a PD-1–blocking antibody-based regimen.
On July 30, the FDA convened the Cellular, Tissue, and Gene Therapies Advisory Committee Meeting to discuss this application. The meeting included a public hearing section to hear from patients, patient advocates, clinicians, and independent experts, followed by a session for discussion and deliberation among committee members.
The approval was granted under the FDA's accelerated approval pathway based on objective response rate and duration of response. As a condition of accelerated approval, Replimune, Inc, is required to conduct postapproval trial(s) to verify and describe the clinical benefit of vusolimogene oderparepvec in combination with nivolumab. Continued approval may be contingent upon verification of clinical benefit in confirmatory trial(s).
IGNYTE
The safety and efficacy of vusolimogene oderparepvec were evaluated in IGNYTE (ClinicalTrials.gov identifier NCT03767348), an open-label, multiregional, single-arm trial in 140 adult patients with stage IIIB, IIIC, or IV unresectable advanced melanoma who experienced disease progression on at least 8 consecutive weeks of prior anti–PD-1-based therapy. Of the 140 patients, 91 patients with at least one noninjected lesion were included in the efficacy-evaluable population.
The major efficacy outcome measures were objective response rate and duration of response. The objective response rate was 24.2% (range = 15.8%–34.3%) and the median duration of response was 14.1 months (range = 10.7 months to not reached).
The prescribing information includes warnings and precautions for accidental exposure, herpetic infection or reactivation, injection procedure complications, and immune-mediated events. The most common non–laboratory adverse reactions reported in more than 10% of patients were 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.
Recommended Dosage
The recommended dosage of vusolimogene oderparepvec is 1 mL/cm of the largest dimension of the tumor, for a maximum of 10 mL across all lesions treated per dose. The size of each injectable lesion should be assessed on each treatment day to determine the required vusolimogene oderparepvec volume. If multiple tumors are present, clinicians should prioritize the most rapidly growing and largest new or existing lesions suitable for injection. Intratumoral injections of vusolimogene oderparepvec should be administered every 2 weeks for eight consecutive doses, beginning at a concentration of 10⁶ plaque-forming units (PFU)/mL at week 1, followed by 10⁷ PFU/mL for subsequent doses.
Nivolumab should be administered intravenously starting at week 3, according to the nivolumab prescribing information.
Vusolimogene oderparepvec-wtpg in combination with nivolumab was granted Breakthrough Therapy designation.
