At the 2023 ASCO Genitourinary Cancers Symposium, Siamak Daneshmand, MD, Norris Comprehensive Cancer Center at University of Southern California—Los Angeles, CA, shares results from Cohort 3 of a phase 2 trial evaluating erdafitinib among patients with BCG-unresponsive, intermediate-risk non-muscle-invasive bladder cancer with FGFR3/2 alterations.

Transcript:

Hi, this is Sia Daneshmand. I'm a professor of urology at University of Southern California, Norris Comprehensive Cancer Center in Los Angeles, and I wanted to share with you our abstract that was just recently presented at the 2023 ASCO Genitourinary Cancers Symposiumin San Francisco entitled "Phase 2 study of the efficacy and safety of erdafitinib in patients with intermediate-risk non-muscle-invasive bladder cancer who harbor FGFR3 alterations." Now, this is part of the THOR-2 study, and this is a cohort 3 interim analysis. There are 2 cohorts in the original THOR-2 study that are ongoing, and this was an exploratory analysis of that study looking at intermediate-risk patients.

The original THOR-2 study is focused on patients with bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer, but it's the same drug, very similar design, oral erdafitinib for the treatment of these patients. The difference here is these are, again, intermediate-risk patients, so these are patients with recurrent low-grade tumors that are deemed to be very low risk for progression. This is traditionally a patient population that we treat either with surveillance, observation, or occasionally we'll use intravesical chemotherapy for these patients. This is one of the first trial looking at using an oral agent in a patient who has FGFR3 alterations; this is targeted therapy. What's interesting is in low-risk tumors or low-grade tumors, the FGFR3 alterations are seen in higher frequency than they are within high-grade tumors. In this cohort, it's supposed to be about 80%, and that's what we're seeing in practice. Most of the patients we screened ended up being positive and were eligible for this trial.

In this trial, we had intermediate-risk disease, usually multifocal low-grade Ta disease, and the patient had had a history of recurrent low-grade Ta disease. We resected most of the tumors but left at least 1 marker lesion measuring 0.5 to 1 centimeter. In essence, this is a marker lesion study, which is a design that's been used in the past, obviously. This interim analysis was to look at the safety and efficacy of using oral erdafitinib in these patients. Patients were given oral erdafitinib for 3 out of the 4 weeks. These are 6 mg doses, lower than the 9 mg doses used in metastatic setting. 11 patients had been dosed up until the deadline for the meeting. Almost all the patients had Ta tumors, and they all harbored the FGFR3 mutations.

We had 8 patients who were evaluable at the cutoff for this presentation, and 6 of the 8, so 75%, had a complete response. This is the marker lesion disappearing. Pretty remarkable, and this happened quickly. We did many of the assessments at 6 weeks to make sure that no one's progressing and again at the usual 3-, 6- and 9-month mark. Even early on we saw some complete responses. One patient had a partial response, and then the other had not had a response yet. Median duration of response has not been reached. All 7 patients who had a response, those 6 complete and 1 partial response, had ongoing at that time of data cutoff. Now, this cohort overall is 20 patients. There are some encouraging results coming from the rest of the cohort as well.

In terms of safety, this was fairly well tolerated. Again, it's a lower dose than the 9 mg that's used for metastatic disease. In terms of grade 3 treatment-related adverse events, there were only 2 of those. One was thought to be treatment-related. No deaths in this study, and nobody discontinued treatment because of it. Almost everybody gets the hyperphosphatemia, and most of those are asymptomatic, 90% of the patients get that. There were 5 patients who had some diarrhea, 5 patients with dry mouth and 3 patients with dysgeusia. Again, none of these were bad enough to discontinue treatment. There was only one grade 3 event, of diarrhea. Fairly well tolerated, and really incredible results, especially this visual of going in there with the cystoscope and looking at the tumor that has disappeared. And we are taking photos pre- and post-treatment to make sure we have photo documentation of these lesions gone away.

Again, this was just an exploratory analysis of 20 patients. The rest of the THOR-2 study is ongoing for patients with high-risk, non-muscle-invasive bladder cancer who are unresponsive to BCG, and those also show encouraging results. There was a poster at ASCO GU Symposium looking at response rates. The interim analysis of that study as well had very, very encouraging results, with most patients having a good response. The safety data is consistent with what we already know about erdafitinib. I think this is really encouraging news that we can use targeted therapy in these patients with intermediate-risk disease, and we're looking forward to future studies looking at this as a potential option for patients.

Source:

Daneshmand S, Zaucha R, Gartrell BA, et al. Phase 2 study of the efficacy and safety of erdafitinib in patients (pts) with intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC) with FGFR3/2 alterations (alt) in THOR-2: Cohort 3 interim analysis. Presented at 2023 ASCO Genitourinary Cancers Symposium; February 17-19; San Francisco, CA. Abstract 504