Tumor-Directed Oncolytic Therapies for Melanoma and CSCC


An expert panel discusses the use of tumor-directed oncolytic therapies for melanoma and cutaneous squamous cell carcinoma.


Sunandana Chandra, MD, MS: Let’s switch gears and talk about the treatment modality of tumor-directed oncolytic therapies. These are intralesional therapies that many medical oncologists often employ in our practices. Dr Khushalani, when do you consider usage of this particular treatment modality for your patients?

Nikhil Khushalani, MD: Specifically for squamous cell, melanoma, or both?

Sunandana Chandra, MD, MS: For either.

Nikhil Khushalani, MD: Obviously in melanoma, we already have an approved agent with T-VEC [talimogene laherparepvec]. T-VEC has been around for several years now, an attenuated oncolytic herpetic virus. This is appropriate in patients who have localized disease, locoregional disease, in-transit metastases, or limited soft tissue metastases because it has the advantage of local therapy with fairly low-risk toxicity with no major systemic toxicity except for what we have seen in the first 24 to 48 hours as a mild constitutional illness. It has the added benefit of eliciting a systemic immune response, as we saw in the registrational OPTiM trial. So I think there is a niche for intralesional therapy in the treatment of patients with melanoma who have visible or injectable disease.

Similar efforts have been undertaken in cutaneous squamous cell carcinoma. As you pointed out, many of these patients present with visible, locally advanced disease that can be injected. There are several compounds now being tested for intratumoral therapy. The one that is probably the [furthest] along is RP1 [vusolimogene oderparepvec]. Again, I would call that the equivalent of a second-generation T-VEC that has the advantage of having the GALV-RP protein in it. That potentially enhances immunogenicity, but also enhances a systemic immune response. We are waiting for data from the CERPASS study, which looked at cemiplimab alone vs combination of cemiplimab plus intralesional RP1. We participated in that trial, and we hope to see some of the data probably sometime this year.

There are a variety of other intralesional agents, including the TLR [toll-like receptor] agonists that are in play. Other oncolytic viruses have been investigated across the spectrum of cutaneous malignancies, but none [have] been approved at this point. These can be utilized for localized disease. There’s certainly the issue of scheduling these patients, making sure you have the right personnel to inject. You have to have an office that is equipped to deal with this, including the biologic agents and [proper] disposal. But if done well with a well-defined workflow, this can become a very good treatment option for a niche population.

Sunandana Chandra, MD, MS: Based on what you just said, Dr Khushalani, and MASTERKEY trial data, do you ever combine anti–PD-1 [therapy] and T-VEC, for example, in a patient with melanoma?

Nikhil Khushalani, MD: Yes, we have done it. But the data eventually panned out as being a negative trial, where the combination did not improve outcomes compared with an anti–PD-1 alone. One could argue that the design of the study may not have been optimal to answer that specific question. At Moffitt [Cancer Center], we have the luxury of a very good practice for intralesional therapy that’s led by [Jonathan Zager, MD, Amod Sarnaik, MD, and Vernon Sondak, MD] on our surgical oncology team. We have treated a large number of patients with intralesional therapies, specifically T-VEC, but also on other clinical trials. The team here has published on multiple occasions in peer reviews and clearly demonstrated the safety of the two together. Again, there is probably a small group of patients it may be appropriate for, but it’s not FDA approved in combination, therefore we have to choose our patients carefully. I think Dr Pavlick said it best, each patient in front of us is his or her own control, and we have to treat [them] independently.

Transcript edited for clarity.

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