The FDA's accelerated approval of vusolimogene oderparepvec (Tudriqev, Replimune) in combination with nivolumab for advanced melanoma — after two prior rejections — has renewed interest in intratumoral immunotherapy. The approach involves injecting therapy directly into a tumor to achieve high local drug concentrations while also triggering a broader systemic immune response that could attack tumors beyond the injection site. But experts remain divided on whether that cascade effect is real and reproducible.

The approval was contentious: the company reported a 33.6% objective response rate from the single-arm IGNYTE trial, while the FDA settled on 24.2%. The advisory panel voted 10-3 in favor, though dissenters noted the trial couldn't isolate how much of the benefit came from the injected drug versus nivolumab. Because approval was based on surrogate endpoints, continued approval hinges on confirmatory trial results. The broader field has seen more setbacks than wins — including a failed phase 3 trial of T-VEC plus pembrolizumab — though a 2025 trial of neoadjuvant daromun in stage III melanoma showed improved recurrence-free survival.

Key Takeaways:

• Vusolimogene oderparepvec + nivolumab is approved for melanoma that progressed after anti-PD-1 therapy, but only under accelerated approval pending confirmatory data
• Objective response rate discrepancy (company: 33.6% vs. FDA: 24.2%) raises questions about endpoint reliability
• Demonstrating responses in non-injected lesions remains a key unresolved challenge for the field

Why it matters: Intratumoral immunotherapy holds theoretical promise for hard-to-treat cancers, but the field needs rigorous randomized evidence to move from concept to standard of care.