Emerging Treatments for Advanced Melanoma  

Evan J. Lipson, MD: There are 2 therapies that have been talked about of late that I get questions about frequently. One of them is a newly approved triple therapy combination, and the other is an experimental agent that had some recently published trial data.

First, the study called IMspire150 looked at a combination of 3 agents; atezolizumab, cobimetinib, and vemurafenib, and it was compared against cobimetinib and vemurafenib as a dual therapy. What this study did not contain was an immunotherapy-only arm.

This was a double-blind, randomized, placebo-controlled trial of about 500 patients, and the primary efficacy outcome was investigator-assessed progression-free survival [PFS], and the trial did go on to meet its primary end point. Median PFS in the triple therapy arm was about 15 months, and in the placebo arm, which contained just the cobimetinib plus vemurafenib, it was about 10 months. There was no atezolizumab-only arm.

In July of 2020, based on those results, the FDA approved atezolizumab in combination with cobimetinib plus vemurafenib for patients with BRAF V600-mutated unresectable or metastatic melanoma.

The tricky part of this study is finding the right patient population in which to use it. It’s not exactly clear what that patient population is right now. Some additional study needs to be done looking at this triple combination in specific patient populations. The triple therapy is now approved and ready for some further investigation. At the moment, it’s just not clear exactly who it’s best for.

One of the other recent developments is some published data with respect to a drug called lifileucel. Lifileucel is a commercially developed tumor-infiltrating lymphocyte [TIL] therapy. Tumor-infiltrating lymphocytes is this concept where, if you take a melanoma tumor out of a person, you’ll see that there are lymphocytes among the tumor cells: immune cells that have infiltrated the tumor. The idea is that if you can get those particular lymphocytes activated in just the right way, you can then give those TIL cells back to the patient and see some antitumor efficacy now that those TILs have been activated.

The study that was just discussed at ASCO [the American Society of Clinical Oncology annual meeting] 2020 was a phase 2 open-label study using lifileucel in patients with unresectable metastatic melanoma who had progressed on checkpoint inhibitors, and if they were BRAF V600-mutated, also on BRAF/MEK inhibitors.

This is a pretreated population that’s already progressed through anti–PD-1, and it wasn’t a huge study. It was only 66 patients, but it was an impressive response rate. The overall response rate was 36.4%, so more than a third of patients responded in this heavily pretreated metastatic melanoma population. These patients often had high baseline disease burden; they had progressed on prior therapies, so this is a tricky population to treat.

We certainly need a lot more data about how effective this therapy can be and what some of the safety signals are. This is a treatment that requires some logistical considerations to get it up and running, but with a response rate like that, of 36% in a heavily pretreated population, there’s reason to be optimistic.

Transcript edited for clarity.