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Dr. Matin on a phase 1b study of infigratinib in localized UTUC

Commentary
Video

“What we find here was that of the patients who had FGFR3 alterations, 67% of them had tumors that responded,” says Surena F. Matin, MD.

In this video, Surena F. Matin, MD, discusses the background and key findings from the study, “Phase 1b trial evaluating tolerability and activity of targeted fibroblast growth factor receptor inhibition in localized upper tract urothelial carcinoma,” for which he served as the lead author. The phase 1b study (NCT04228042) evaluated the use of infigratinib, a fibroblast growth factor receptor (FGFR) inhibitor, in patients with upper tract urothelial carcinoma (UTUC) with or without FGFR3 alterations. Matin is a professor of urology and surgery at MD Anderson Cancer Center in Houston, Texas.

Video Transcript:

This trial was set up as a phase 1b trial because we've never tested these compounds in the non-metastatic setting. One thing we've learned in our group from many years of doing neoadjuvant and adjuvant therapy is that patients with localized disease are a very different population than those with metastatic disease. Their tolerability for drugs that are used in the metastatic setting is not going to be the same; you can't make the same assumptions. First of all, we wanted to see is it tolerable, and is it safe? Because these drugs do have a side effect profile. Which, in someone whose life is immediately threatened by their condition, they may put up with, but in someone who has a longer lifespan and not a life-threatening disease, they may not tolerate. So, that's why this was set up as a tolerability trial primarily. As a close secondary end point, we wanted to, of course, look at tumor responses.

The way this trial was set up was a window of opportunity trial, basically like a preoperative trial. [We offered this] to patients who were going to have surgical treatment with either endoscopy or surgical removal of the kidney and ureter. It was treatment for about 7 weeks, and then surgery would be performed. Patients did have to have a residual tumor, and we performed a tumor map after any biopsies or lasering that may have been done at the time of endoscopy. Then, at the surgical treatment, after the drug trial treatment, we did a second tumor map. The difference between those findings is what provided the response data that we have. This essentially mimicked the way things were done for the registration trial for the mitomycin hydrogel compound. That set up a standard for what is acceptable by the FDA, and that is how we modeled this trial also.

What we find here was that of the patients who had FGFR3 alterations, 67% of them had tumors that responded. The average [tumor size reduction] was 67% also. So, two-thirds of the patients with the mutation had a response, and the responses were pretty dramatic considering this was a very short duration of treatment. [It was] 6 to 7 weeks of treatment. With the particular compound that we used, it was essentially 2 cycles, [conducted as] 3 weeks on, 1 week off, and then 3 more weeks, and then that was it. So, [we saw] pretty dramatic responses. And [3 out of 5] of those patients who were initially deemed to go on to nephroureterectomy were able to be converted to endoscopic management. They had so much volume disease or so much multifocality, that once there was so much size reduction, they became eligible for endoscopic management. For us, that gave us a perspective in terms of how this intervention could be used in a future trial, and potentially in clinical care.

The one thing I didn't touch on was the tolerability aspect, our primary end point. That was better than we expected. We did have a continuous monitoring plan, a Bayesian statistical plan, that would continuously monitor patients. The trial did end early because the drug supporter pulled the drug from the oncology market and indications and trials that were going on. There were multiple trials affected by this internationally. The good news for us is that we had enrolled 14 out of 20 patients. Out of those 14, only 2 didn't tolerate the full 2 cycles of the drug. That was well below our safety threshold, meaning, even if all the next 5 patients didn't tolerate it, we would still have met the tolerability criteria. So, we were well below that aspect of it. I think part of that speaks to the fact that it is a very short duration treatment.

This transcription has been edited for clarity.

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