Robert L. Coleman, MD: Hi everyone. My name is Dr. Rob Coleman. I'm a gynecologic oncologist in Houston, and I'm joining you today from the SGO Annual Meeting on Women's Cancer here in Tampa, Florida. And I'm here to present the update on the SORAYA trial. It's great to be with you.
OBR: The main results of SORAYA supported FDA approval for mirvetuximab soravtansine. Can you tell us about the new analysis you've presented at SGO?
Dr. Coleman: So many of the viewers will remember that last year we presented the objective response rate and duration of response and toxicity from the top-line data from this trial. This did lead to an FDA accelerated approval in November of last year, and so this became an agent that's been available to us. This year, what we wanted to do was provide more nuance around the types of the response rates that we saw in the various different types of patients who participated on the trial, as well as a matured analysis of overall survival.
OBR: Why is it important to look at responses or response patterns in such detail?
Dr. Coleman: So it's important to look at responses across the population that were enrolled in the study, because we have some heterogeneity in the patients that were able to participate in the trial. One of the key features in trials that are addressing patients with recurrent platinum resistant ovarian cancer is how many lines of prior therapy they received and when in those lines of therapy did they receive the actual experimental compound here. So mirvetuximab.
The other component of this that's important is that patients nowadays are seeing agents such as the PARP inhibitors in various different settings. Today in 2023, we're seeing this predominantly in the frontline setting. And so, it was important for us to look at the activity of this compound in patients who had had exposure to these multiple lines of therapy and to agents like a PARP inhibitor.
Importantly in this trial, all the patients were exposed to Bevacizumab, but in the study that bevacizumab could come in one of three different contexts. One could be in the frontline setting. Two, it could be in the platinum sensitive recurrent setting. Or three, it could be in the platinum resistant recurrent setting. So we wanted to evaluate the efficacy of this drug in those subgroups.
OBR: Given what you found, how do you recommend using MIRV in the clinic?
Dr. Coleman: Well, the way we would use this drug in the clinic would be most accurately aligned with the patients that went into the study. So as mentioned, we felt that the number of lines of therapy that patients that were in this trial were consistent with the types of patients who we'd see in the clinic. The prior exposure would be consistent with what we see in the clinic. And importantly in this trial, it was an absolute requisite that they have high level of expression of folate receptor alpha, which was identified from our previous work to be important to optimizing the efficacy signal. So in this trial, we would, just as it's available to our practitioners now as under the accelerator approval, we can be confident in what we see in terms of objective response among these various different cohorts in patients whose tumors have high expression of folate receptor alpha.
OBR: Are there patients who meet the study criteria but for whom MIRV isn't the right choice?
Dr. Coleman: There are some patients that would not be good candidates for the drug, probably the most common of which would be those that are kind of on the borderline of having preexisting toxicities that might lead to potential acceleration of that. Fortunately, with this particular compound, we didn't see a lot of toxicity that was not able to be mitigated. But there are some patients that are more sensitive to these drugs or this class of cytotoxic agent or who, for instance, have a preexisting neuropathy. These would be patients that we would have to be more careful about counseling and selecting them carefully.
The other group of patients that might not, that weren't really excluded from the trial, but we want to be more mindful of them, are those that have visual issues, particularly with corneal and visual acuity, since these were common side effects. Or those that have preexisting dry eyes where this could potentially can be made worse on therapy.
We were very careful in this study in making sure that we had patients that weren't going to have an acceleration of preexisting toxicities. But when these drugs become available to the broader population, we have to be mindful that these particular exclusions existed to help prevent the acceleration of toxicity. So we would be mindful of factors that we normally treat with chemotherapy, such as preexisting bone marrow issues, but unique about this compound would be also some things like visual issues, particularly if a patient is dependent on using contact lenses, those types of issues, that we would want to be careful about.
OBR: Are there other things about this trial or drug you think oncologists should know?
Dr. Coleman: I think oncologists need to be comfortable with the eye care plan. Fortunately, many of the GYN community and also now the medical oncology community have had a fair amount of experience with dealing with ocular adverse events with antibody drug conjugates that we've seen in the past. The one thing to remember is that the ocular toxicities that we saw with this particular drug are different than the ocular toxicities you see with other ADCs. And so it's important that the practitioner be knowledgeable of the drug specific adverse events that come with this particular agent.
The good news with this agent is that although we saw toxicity ocular events in about half the patients, nearly all of them were reversible and reversible in a short period of time without in general requiring much in the way of dose modification. So, I think we can be more confident that this is something that realistically can be delivered in the clinic, in an outpatient setting, and one that has high levels of efficacy that we'd love to be able to give to our patients.
