Positive data reported for hydrogel-based urothelial Ca agent

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“The high initial complete response rate and durability observed in the interim analysis is very promising and suggests that UGN-101 could be an effective and well-tolerated noninvasive treatment for patients with UTUC,” says researcher Seth Paul Lerner, MD.

Clinicians may soon have a new non-surgical approach to offer patients with low-grade upper tract urothelial cancer (UTUC).

Researchers presented findings at the AUA annual meeting in San Francisco demonstrating that UGN-101 (MitoGel), an investigational mitomycin formulation, may be a new non-surgical treatment option for patients with UTUC. The interim analysis from the ongoing international multicenter phase III OLYMPUS clinical trial showed a complete response rate of 59% in 34 patients who were evaluated for primary disease evaluation (PDE), which was the primary endpoint. PDE involves the use of ureteroscopy and wash cytology.

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PDE was conducted 4 to 6 weeks after completion of UGN-101 treatment, which was administered once weekly for 6 weeks. The authors found that 20 of the interim analysis intent-to-treat population achieved a complete response, which was defined as a negative ureteroscopic evaluation and a negative wash cytology. In addition, five of 34 patients (15%) achieved a partial response.

“The complete responses have been durable at 3-month follow-up, 6 months, and 9 months. The high initial complete response rate and durability observed in the interim analysis is very promising and suggests that UGN-101 could be an effective and well-tolerated noninvasive treatment for patients with UTUC, potentially sparing them from invasive surgery to remove their kidney,” said principal study investigator Seth Paul Lerner, MD, of Baylor College of Medicine, Houston.

In this current investigation, approximately 39% of tumors treated were categorized as unresectable by surgery at baseline. Among the 20 patients who achieved a complete response, 13 patients have reached 3-month follow-up and all remain in complete response. Four of these 13 patients have reached 6-month follow-up and one of the 13 patients has reached 9-month follow-up. All remain in complete response.

Next:Treatment appeared to be well toleratedUGN-101 appeared to be well tolerated, with most treatment-emergent adverse events characterized as mild or moderate and transient. The adverse events included urinary tract infection, flank pain, ureteral narrowing and hydronephrosis, and time-limited creatinine elevation. Mark Schoenberg, MD, chief medical officer of UroGen, said these findings are promising and demonstrate the potential of UGN-101 to become the first drug ever approved for low-grade UTUC.

“It could be approved in the next 6 to 9 months,” Dr. Schoenberg said in an interview with Urology Times.

OLYMPUS (Optimized DeLivery of Mitomycin for Primary UTUC Study) is an open-label, single-arm phase III clinical trial of UGN-101 and is anticipated to enroll approximately 74 patients at clinical sites across the United States and Israel.

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UGN-101 is an investigational drug formulation of mitomycin that utilizes the RTGel technology platform, UroGen’s proprietary sustained-release, hydrogel-based formulation. This is designed to allow longer exposure of mitomycin C to the urinary tract tissue, thereby potentially enabling the treatment of tumors via non-surgical means. The FDA has granted both Orphan Drug and Fast Track designations to UGN-101 for the treatment of low-grade UTUC.

“Despite advances in endoscopic management of low-grade UTUC, nephrectomy is often required to manage recurrent, large-volume, or inaccessible tumors in the renal pelvis. The high complete response rate observed in this interim analysis are encouraging and, if borne out through the rest of the trial and consistently durable, these data suggest that this novel chemoablation treatment approach may help patients avoid or delay the need for nephrectomy,” Dr. Lerner told Urology Times.

Dr. Lerner has received compensation for serving on a UroGen advisory board, and his institution receives funds for his role as principal investigator of the OLYMPUS trial.