Hey everyone — it’s been a busy stretch, and I’m genuinely grateful for all the encouragement and support along the way. Behind the scenes, we’ve been working to bring several new clinical trial options to our patients here at AdventHealth — Immatics’ SUPRAME study, Obsidian’s engineered TIL program in melanoma and lung cancer, Iovance’s TILVANCE-301 bringing TIL therapy into the first-line melanoma setting, and Immunocore’s PRISM-MEL-301 trial — with a few sarcoma studies in the works as well. Hopeful we’ll have several of these open for enrollment in the coming weeks. But today I wanted to pause and share something that’s already here, not just hoped-for: a new FDA-approved option for our patients with PD-1-refractory melanoma.
Over the past decade, I’ve injected a lot of things directly into tumors. Modified herpes virus. Poliovirus. TLR9 agonists. Various cytokine approaches. Each one chasing the same idea: turn the tumor into its own vaccine, and wake up an immune system that’s stopped paying attention. Most of these approaches share the same limitation, though — they work best on what you can see and reach. Skin. Lymph nodes. The moment disease moves into the liver or the lungs, the options narrow fast.
This week, that limitation got a little smaller.
On August 6, the FDA granted accelerated approval to vusolimogene oderparepvec-wtpg — now marketed as Tudriqev — in combination with nivolumab, for adults with advanced melanoma that has progressed after anti-PD-1 therapy. Most of us in this field still know it by its old name: RP1.
Getting here wasn’t simple. This was Replimune’s third attempt at approval, after two rejections. The FDA’s concerns were legitimate ones — separating out how much of the benefit came from RP1 itself versus nivolumab, a patient population that varied widely in prior treatment, and response assessments complicated by surgical interventions along the way. Real questions, the kind that should slow a drug down. Then, on July 30, an advisory committee weighed the data against the reality of the disease and voted 10 to 3 in favor. A week later, the approval came through.
What makes this one different for me isn’t just that it’s another local therapy option. T-VEC, the original oncolytic virus approved back in 2015, is a good drug — but it’s really a skin-and-lymph-node drug. Once melanoma moves into the liver, T-VEC’s usefulness drops off fast. The trial behind Tudriqev included injecting the liver and lung directly, working alongside interventional radiology to reach lesions that used to be out of range for this kind of local therapy. And the response didn’t stay local — lesions that were never injected responded too, in the large majority of cases. That’s the systemic, abscopal-style effect actually doing what it’s supposed to do, not just a theory in a review article.
The numbers the FDA approved on are worth being precise about, because two different data sets have circulated for this drug and they answer different questions. The approval itself is anchored to a specific group of patients — those with at least one lesion that was never injected — and shows a 24% response rate, with responses lasting a median of just over a year. That’s a deliberately conservative way of proving the drug’s effect is coming from the immune system, not just the needle. Earlier data presented at ASCO, from the full trial population, looked more favorable. That gap between the early numbers and the final approved numbers is part of why this took three tries — the bar wasn’t just “encouraging trend,” it was proof that held up.
Where I think this actually lands, in practice, is with a specific group of patients. Those who’ve progressed on PD-1 therapy, don’t have a targetable mutation to fall back on, aren’t candidates for a clinical trial, and aren’t strong enough for something like TIL therapy — often older or more frail patients who still deserve a real option, not just a harder conversation. For that group, this is now something concrete instead of a shrug.
It’s still an accelerated approval, not a final one. A confirmatory trial is underway, still enrolling, still years from reading out, and full approval depends on what it shows. But for now, three tries later, the door is open a little wider than it was a week ago.
I’ve watched a lot of promising therapies in this space fail to make it across the finish line. Watching one get there — on the third attempt, no less — is a good reminder that “no” isn’t always the end of the story.
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. He brings a wealth of expertise to the complex and challenging world of oncology.
Disclosures:
Dr. Thomas serves as a speaker for BMS, Merck, Ipsen, Natera, Immunocore, Pfizer, Sun Pharma, SpringWorks. He also receives industry grants in support of numerous clinical trials.
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