Q&A: What Tudriqev's Approval Means for PD-1-Refractory Melanoma

The FDA's accelerated approval of Tudriqev (vusolimogene oderparepvec-wtpg; formerly RP1) in combination with nivolumab provides another treatment option for adults with unresectable or metastatic cutaneous melanoma who have progressed on anti-PD-1 therapy.¹

In a recent interview with Dermatology Times, Joan Levy, PhD, chief science officer at the Melanoma Research Alliance (MRA), discussed the significance of the approval, the systemic responses observed with the combination, the multidisciplinary coordination required for treatment delivery, and what the melanoma community will be watching as the confirmatory IGNYTE-3 trial continues.¹

Levy also highlighted emerging combination strategies being investigated for patients with anti-PD-1-refractory disease and the role of patients, caregivers, clinicians, researchers, and advocacy organizations in advancing melanoma treatment.

Dermatology Times:

From MRA's perspective, how significant is this approval for patients who have progressed on anti-PD-1 therapy?

Levy:

From the MRA perspective, this accelerated approval was very significant. Approximately 8,500 patients die from melanoma each year. The melanoma field has made enormous strides over the last 2 decades, with 20 drug approvals, and that's fantastic for patients. But we also know that over 50% of patients will progress after a PD-1-based regimen.²

There's still a lot more that needs to be done to bring treatments to those patients. There have been a limited number of options, and some advanced patients might not be eligible for the options that are available.

We really needed to increase the toolkit of options available. The approval of Tudriqev, or RP1, in combination with nivolumab for adults with unresectable advanced cutaneous melanoma adds another option to that toolkit. We felt this was a very significant need, and we're excited and pleased that this is now an option for advanced melanoma patients.

Dermatology Times:

Objective response rates and duration of response held up in patients with harder-to-treat disease, including liver and lung involvement and PD-L1-negative status. What does that durability tell you?

Levy:

The durability tells us a few things. The oncolytic virus gets injected into the tumor and can kill the tumor, but what's really important with this oncolytic virus is that it could also trigger a more systemic response, and that could be enhanced by combining it with an immune checkpoint inhibitor.

The local response primes immune cells that are able to recognize and attack melanoma cells in distant parts of the body, including distant liver and lung metastases and even metastases that were not injected with RP1.

The durability shows us that this treatment could elicit more of a systemic response, which we were hoping it could do. It's providing evidence that this could be the case.

We call it the abscopal effect. The immune response is spreading to other areas and to lesions that haven't even been injected. Some visceral lesions can be injected with RP1, but this systemic response appeared to occur even when not everything was injected.

Dermatology Times:

RP1 can be delivered by direct injection, including into visceral lesions under imaging guidance. What does this delivery approach mean for treatment sequencing and referral patterns in advanced melanoma?

Levy:

In many cancers, you need a multidisciplinary approach to treat an advanced cancer patient. This is another situation where it's going to take a multidisciplinary approach.

If it were just a viral injection directly into a superficial tumor, it could be done by specialized dermatologists or surgical oncologists. But now we have it in combination with systemic treatment, so that brings in medical oncologists to help time it with the delivery of nivolumab.

There are also visceral lesions, and those lesions really need an interventional radiologist because they require image-guided injections.

It is going to take coordination. This is done in different cancers where physicians from different specialties have to coordinate among themselves, and it's doable. Especially since visceral lesions can be injected, that's a major accomplishment because other oncolytic therapies were more locally injected into superficial lesions.

It is going to involve coordination and thought, but I have confidence that our medical community will be able to continue to work together and figure it out.

Dermatology Times:

Are you seeing any hesitancy among patients toward trying this type of therapy, or has the response generally been positive?

Levy:

After the approval, we had a lot of patients calling and expressing their enthusiasm about having another treatment option. We've heard more from patients who are very pleased that they could have this type of therapy and another option in a limited toolkit for this patient population.

I don't think we've heard from many patients with hesitancy. I'm more on the science side, but I haven't heard from our communications and engagement team that there has been a lot of hesitation.

We need to educate patients on how this works, and we have to do more education about it. We and many other foundations are prepared to do that. Many foundations already have information on their websites providing patients with information, and there have been webinars and other educational materials discussing this type of therapy.

We'll continue to educate patients, listen to their positive responses as well as any concerns, and provide them with the resources they need to make a decision.

Dermatology Times:

Tudriqev received accelerated approval, with the confirmatory IGNYTE-3 trial still ongoing. How should patients and families understand the distinction between accelerated and full approval?

Levy:

It's really important for patients to understand what accelerated approval means and why there has to be a confirmatory trial.

Accelerated approval is intended to facilitate bringing therapies to patients earlier. It uses surrogate end points such as response and tumor shrinkage that are considered likely to predict clinical benefit.

By clinical benefit, we mean things like improving overall survival and progression-free survival. The thought is that these earlier readouts in response and durability are likely to predict that clinical benefit.

That's where the confirmatory trial comes in. The confirmatory trial is measuring clinical benefit, including overall survival and progression-free survival, as well as a number of other parameters.

You have to wait for the confirmatory trial to read out, which could take several years because survival is a longer end point. If the confirmatory trial meets its end points, then it could lead to full approval.

I think it's important to explain that distinction to patients, while also recognizing that accelerated approval allows patients to receive the treatment.³

Dermatology Times:

What will you be watching for as IGNYTE-3 continues and eventually reads out?

Levy:

In every clinical trial, whether it's phase 1, 2, 3, or a confirmatory trial, we always look for continued safety. Safety was mild to moderate in the IGNYTE-2 trial, so that's something that will continue to be monitored in this larger population.

Of course, we also want to see clinical benefit. Measuring overall survival and progression-free survival is going to take several years because you have to enroll a certain number of patients and then follow those patients.

I'd also like to continue to see evidence for a systemic response, including responses in uninjected lesions. That will ultimately also be reflected in overall survival and progression-free survival.

For foundations like MRA, it's also very important to make sure the confirmatory trial is enrolling patients and meeting its enrollment numbers. Without those enrollment numbers, you won't be able to have a full confirmatory trial meet its end points.

We make patients aware of this trial as well as other trials. We have our Clinical Trials to Watch program across a number of open clinical trials for melanoma patients. Making sure trials are enrolling is something we like to watch and help promote.³

Dermatology Times:

Looking beyond this approval, where do you see the next opportunities for combination approaches in anti-PD-1-refractory melanoma?

Levy:

There are a number of different strategies being developed to combine with nivolumab or other PD-1 regimens. There are additional checkpoints that drugs are being developed against so they can potentially be combined. There are also treatment vaccine approaches being considered in combination with anti-PD-1 regimens.

There are cell-based approaches, including tumor-infiltrating lymphocytes, as well as CAR T-cell and TCR-T therapies being developed, with thoughts of combining these with immune checkpoint inhibitors.

There are also other types of combination approaches being actively pursued. One exciting approach is bispecific antibodies. With a bispecific antibody, you have 2 different arms built into 1 antibody. One can act against PD-1, while the other works against another target.

For example, VEGF/PD-1 bispecific antibodies are being developed by a number of companies. One antibody could affect 2 different targets, including PD-1 and VEGF or VEGFR.

Antibody-drug conjugates are another approach that's very popular in the industry right now. The antibody recognizes something on the surface of a tumor cell and is conjugated to a chemotherapeutic or cytotoxic drug. It brings that drug into the tumor cell, allowing you to target the tumor cell rather than exposing the patient to the same systemic effects.

It's another type of combination approach. Instead of giving 2 drugs, it's more of an all-in-one approach combining different factors.

Dermatology Times:

Is there anything else about the approval or the process leading up to it that you think is important for the melanoma community to recognize?

Levy:

We've been following the entire story of RP1 throughout its journey, especially over the last few years. What this really proved to me was the power a community has in helping to get drugs approved and how we can all work together when we rightfully feel a drug should be approved.

There was an advisory committee meeting with a public speaking session where many patients, caregivers, medical oncologists, and advocacy organizations spoke. It was amazing to see sponsors, clinicians, researchers, patients, patient advocacy groups, and caregivers come together with so much passion.

It really shows the power of a community working together. It was an eye-opening experience for me to be part of this, and I'm thrilled that these advanced patients will have another option.

Another important group in that process is the FDA. Being able to discuss information with the agency, present and work with them, and continue to work with the FDA and sponsors in the future is really important.

We've held workshops in the past between the FDA and the melanoma community, and we should continue to do that as an advocacy organization.^1,2

References

1. US Food and Drug Administration. Cellular, Tissue, and Gene Therapies Advisory Committee: July 30, 2026 Meeting Materials. FDA. 2026. https://www.fda.gov/advisory-committees/cellular-tissue-and-gene-therapies-advisory-committee/2026-meeting-materials-cellular-tissue-and-gene-therapies-advisory-committee
2. US Food and Drug Administration. Accelerated Approval Program. FDA. Updated 2026. https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program
3. Replimune Group, Inc. Clinical Trials: IGNYTE-3. https://www.replimune.com/clinical-trials
4. National Cancer Institute. RP1 for the Treatment of Melanoma Undergoing Sentinel Lymph Node Biopsy. National Cancer Institute.
   https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-03864