Paclitaxel-hyaluronic acid conjugate induces CR in 75% of patients with bladder CIS

Intravesical Oncofid P-B, a conjugate of paclitaxel and hyaluronic acid (P-HA), is active in patients with carcinoma in situ (CIS) of the bladder that is not responsive to bacillus Calmette-Guérin (BCG).

In a single-arm, open-label study, the complete response (CR) rate following 12 weeks of intensive treatment with P-HA was 75%, reported Rodolfo Hurle, MD, during the 2020 European Association of Urology Virtual Meeting.¹

With an excellent safety profile coupled with promising efficacy, P-HA “is well positioned as compared with the most recent competitors, thus confirming its potential as a therapeutic option in BCG-unresponsive CIS patients,” said Hurle, of the department of urology, Istituto Clinico Humanitas IRCCS, Clinical and Research Hospital, Milan, Italy.

New drugs able to delay or avoid cystectomy in patients with CIS unresponsive to BCG is an unmet clinical meet, he said.

Oncofid-P-B is a novel water-soluble conjugate of P-HA that has bladder muco-adhesive properties and requires no need for patient premedication. It is said to increase paclitaxel activity in superficial bladder tumor due to specific binding of the HA moiety to CD44, its natural receptor expressed on the bladder tumor surface. The safety, tolerability, and efficacy of weekly administration of 600 mg of P-HA in 50 mL of 5% glucose solution were explored in a phase 1 European multicenter study of 20 patients with CIS unresponsive or intolerant to BCG and who were unwilling or unfit for cystectomy.

During the intensive phase of the study, P-HA was administered by intravesical instillation for 12 consecutive weeks. Patients who achieved a CR in the intensive phase continued treatment in the maintenance phase with 12 monthly instillations. CR was defined as a negative cystoscopy, including biopsy of the urothelium, and negative cytology.

The primary end point was the overall safety profile. Secondary end points included efficacy after the intensive phase.

There were 16 men and 5 women enrolled (20 patients were treated), and the mean age of patients was 72.8 years. All were Caucasian. Seventeen patients had CIS and 4 had CIS plus Ta.

Fifteen of 20 patients (75%) achieved a CR at the end of the intensive phase (3 months). During the maintenance phase, the CR rates at 6, 9, and 12 months from the start of treatment were 65%, 60%, and 45%, respectively. Five patients are still in the maintenance phase.

Seven grade-1 or grade-2 drug-related adverse events were reported in 4 patients (3 cases of hematuria, 2 cases of urticaria, and 1 case each of proteinuria and nausea) over 298 instillations. There were no serious drug-related adverse events and no patient withdrew from the study. P-HA was not detected in plasma at any time point.

Treatment options for BCG-unresponsive CIS are expanding, and have similar rates of response, noted session moderator Thomas Seisen, from Hôpital Pitié‐Salpêtrière, Sorbonne Université, Paris, France. Pembrolizumab (Keytruda) was recently granted FDA approval for this indication, following results from a clinical study demonstrating a CR rate of about 40%. Earlier this year, data were presented at the Genitourinary Cancers Symposium showing a 53.4% CR rate with administration of intravesical nadofaragene firadenovac in patients with high-grade, BCG-unresponsive nonmuscle invasive bladder cancer. Where P-AH may fit into the treatment armamentarium amongst these options for this disease remains to be determined.

Reference

1. Hurle R, Guazzoni G, Colombo P, et al. Preliminary results of a European multicentre phase 1 study with Oncofid-P-B for the treatment of BCG unresponsive carcinoma in situ (CIS) of bladder at the end of 12 consecutive weeks intensive course and during ongoing monthly maintenance phase 2020 European Association of Urology Virtual Congress. July 17-26, 2020. Abstract 768

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