Review of GEMSTONE-301 and -302 Data

Mark Socinski, MD: We talked about new entries to the market. There’s an anti–PD-L1antibody—I hope I’m pronouncing it right—called sugemalimab that we saw some data on. Jack, can you tell us about the GEMSTONE-301 study?

Jack West, MD: Sugemalimab is an anti–PD-L1 antibody. Of course, we have many immune checkpoint inhibitors targeting 1 or the other side of that receptor. What we see is that there were a couple of studies that have gotten a glimpse of activity. The first is a trial that we got some results from within the last year. This was by Dr Caicun Zhou, and it’s GEMSTONE-302, which was a study of chemotherapy and placebo, or this agent, sugemalimab. This study demonstrated a significant improvement in progression-free survival with a hazard ratio of 0.5, which is in line with what we’ve come to hope for or expect to see for combined chemotherapy-immunotherapy, compared with chemotherapy alone because that’s an outdated comparator, in the United States at least. The response rate was also significantly better— 61.4% vs 39% for chemotherapy.

Certainly, the data look encouraging, but isn’t that different from what we would expect to see with a chemotherapy-pembrolizumab regimen. Importantly, this study was in a population with both squamous and nonsquamous, non–small cell cancer. There’s also a press release of a different study called GEMSTONE-301. We have an interim report of this study, which looks at consolidation with this agent. That’s after chemotherapy-radiation given either concurrently—which is what we typically do, as was done in the PACIFIC trial—or sequential chemotherapy-radiation, which is sometimes done at every place, particularly in patients who may not be feasible to tolerate concurrent chemotherapy-radiation. We know that this study also showed a significant improvement in progression-free survival. We have yet to see the details on that, but this is more evidence that this agent is active, and potentially relevant, for additional strategy; particularly in patients who aren’t strong candidates for consolidation after concurrent chemotherapy-radiation. We know that 1 of the limitations, in actual practices, is that lots of patients don’t get through concurrent chemotherapy-radiation because they may have too large of disease, don’t have the pulmonary function, etc. This is another 1 to watch.

Mark Socinski, MD: Yes, it’s going to be interesting to see this story evolve. We assume that many of these PD-1, PD-L1 inhibitors may have similar impacts on the disease in these settings. Getting back to our discussion about the Elsevier pathway, when you make considerations first on efficacy and can’t distinguish a clear choice, there isn’t likely to be a difference in toxicity with regard to these agents, and it’s going to come down to cost at the end of the day. We’ll have to see this evolve over time, and GEMSTONE—both -301 and -302, though -301 is probably more importantly because we have very little competition in that space. GEMSTONE-302, as you made the point, was very similar to what we’ve seen from trials that have changed the standard of care.

Jack West, MD: If something comes in as a lateral move with a significant improvement in cost, then that’s an incremental benefit.

Mark Socinski, MD: Yes, I know. Absolutely. The question is, how much of a cost difference is going to move the needle, and what will people to do with it? Of course, so much of that is done—with collaboration of various third-party payers, with oncology pharmacies, and so on—that we aren’t necessarily involved. Sometimes some people are shielded opinion in regard to how that may impact things. This is part of our purpose of having this discussion.

Transcript edited for clarity.