The US Food and Drug Administration (FDA) has granted accelerated approval to vusolimogene oderparepvec-wtpg (Tudriqev; Replimune, Inc.) plus nivolumab for adults with unresectable advanced cutaneous melanoma whose disease progressed on a programmed death receptor-1-blocking antibody-based regimen.
The approval was based on objective response rate and duration observed in the IGNYTE trial, an open-label, multiregional, single-arm study. The trial enrolled 140 adult patients with stage IIIB, IIIC, or IV unresectable advanced melanoma whose disease progressed following at least 8 consecutive weeks of prior programmed death receptor-1-blocking antibody-based therapy. Efficacy was evaluated in 91 patients with at least one noninjected lesion. In that population, the objective response rate was 24.2%, and the median duration of response was 14.1 months.
According to the agency, Replimune is required to conduct postapproval trials to verify and describe the clinical benefit of vusolimogene oderparepvec-wtpg in combination with nivolumab. Continued approval may depend on confirmation of clinical benefit in postapproval confirmatory trials.
According to the prescribing information, warnings and precautions address accidental exposure, herpetic infection or reactivation, injection procedure complications, and immune-mediated events. Nonlaboratory adverse reactions reported in more than 10% of patients included fatigue, pyrexia, infections, chills, musculoskeletal pain, nausea, diarrhea, injection-site reactions, headache, cough, influenza-like illness, rash, vomiting, pruritus, arthralgia, constipation, decreased appetite, dizziness, dyspnea, hemorrhage, edema, and abdominal pain.
The recommended dosage of vusolimogene oderparepvec-wtpg is 1 mL per centimeter of the largest tumor dimension, up to a maximum of 10 mL across all treated lesions per dose. Intratumoral injections are administered every 2 weeks for 8 consecutive doses, beginning at a concentration of 10⁶ plaque-forming units per milliliter at week 1 and followed by 10⁷ plaque-forming units per milliliter for subsequent doses. Nivolumab is administered intravenously beginning at week 3 according to its prescribing information.
The FDA also noted that vusolimogene oderparepvec-wtpg in combination with nivolumab received breakthrough therapy designation.
Source: US Food and Drug Administration
