Jason M. Broderick

Platelet-rich plasma (PRP) injections appear to be a safe and feasible approach to treating patients with Peyronie’s disease, according to early research shared in a poster during the 2021 Sexual Medicine Society of North America (SMSNA) Fall Scientific Meeting.

First author Kevin Chu, MD, a men’s health fellow at the University of Miami, and colleagues reported data at SMSNA for the first 6 patients enrolled in the study. The patients were randomized to PRP or placebo and completed 2 injections.

“The notable finding to be taken from this abstract is that there were no noted adverse effects for patients that received PRP injections. We had thought there would be some patients with mild ecchymosis or penile pain. This, of course, may change as we enroll more patients into the trial, and our sample size gets larger. But from a preliminary standpoint, it appears to be safe to use in patients with Peyronie’s disease,” Chu said in an interview with 

Explaining the rationale for their study, Chu et al wrote in their poster that 7.1% of the general population has Peyronie’s disease, with use of intralesional collagenase clostridium histolyticum injection being the only FDA-approved medical therapy. They noted that surgical interventions for the condition include tunica albuginea plication, plaque excision without grafting, or placement of penile prothesis.

“Intervention only occurs once the disease process has entered the chronic, stable phase,” wrote Chu et al, adding, “Additional Peyronie’s disease therapies are needed as current treatment modalities have limited efficacy and considerable side effects.”

The increased use of platelet-derived therapies in other healthcare specialties inspired Chu et al to examine the approach in patients with Peyronie’s disease. The investigators were particularly intrigued by the use of platelet-derived therapies in orthopedics for the potential of healing wounds and regenerating tissue. “As calcified scar plaques are frequently identified in Peyronie’s disease patients, autologous PRP may prove to be a viable treatment for this patient population,” wrote Chu et al.

Accordingly, a double-blind placebo-controlled, single-center, randomized clinical trial was launched at the University of Miami Miller School of Medicine to compare PRP with placebo in patients with Peyronie’s disease. Chu et al’s SMSNA poster shared the outcome from their safety and feasibility review of the initial series of patients recruited to the trial.
This study population included men enrolled at the University of Miami trial site between April and July 2021 and treated with PRP versus placebo. For their review, the investigators evaluated patients for complications and tolerability immediately following PRP injection and at follow-up. Patients’ International Index of Erectile Function (IIEF-5) scores were reviewed prior to and following injections where applicable.

According to Chu, “The take-home message from our findings is that PRP appears to be safe for use in patients with Peyronie’s Disease. We are still very early on in our clinical trial, as we expect to enroll a total of 60 patients into the trial. As the trial is a double-blind, crossover trial, we do not have any current information on the actual efficacy of PRP in Peyronie’s Disease.”

Chu added, “It is important for [urologists] to know that the trial is currently ongoing. We hope to have a better idea of the efficacy of PRP for Peyronie’s Disease in 1 year. Restorative therapies for sexual medicine have hypothesized mechanisms for efficacy, but more robust clinical trials in humans are needed to show their true potential. At the University of Miami, we are running randomized clinical trials on PRP and combination (PRP + shockwave therapy) for sexual medicine ailments.”

1. Chu K, Masterson, T, Efimenko, I et al. Safety and feasibility of platelet-rich plasma injections for Peyronie’s disease: update from a single-center double-blind placebo-controlled randomized trial. Paper presented at 2021 Sexual Medicine Society of North America Fall Scientific Meeting; October 21-24, 2021; Scottsdale, Arizona. Abstract 179.

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“Additional Peyronie’s disease therapies are needed as current treatment modalities have limited efficacy and considerable side effects," the authors wrote.

Platelet-rich plasma injections safe and feasible treatment for Peyronie’s disease

The combination of the novel interleukin-15 superagonist N-803 (Anktiva) and Bacille Calmette-Guérin (BCG) met the primary end point of disease-free survival (DFS) in patients with BCG-unresponsive, high-grade non–muscle-invasive bladder cancer (NMIBC) and papillary disease, according to updated findings from the phase 2/3 QUILT-3.032 trial.

The DFS rate was 57% at 12 months and 53% at 18 months. The median follow-up time overall was 17.3 months. The responses were durable, with the treatment enabling 85% of patients to avoid cystectomy.

The papillary group made up cohort B of the QUILT-3.032 trial. Previously reported findings showed that the primary end point was also met in cohort A, which enrolled patients with carcinoma in situ (CIS).

"Intravesical BCG has been the standard of care for more than 30 years for patients with noninvasive papillary tumors, yet, unfortunately some 40% of them don’t respond," Patrick Soon-Shiong, MD, founder and executive chairman and Global Chief Scientific and Medical Officer of ImmunityBio, the manufacturer of N-803, stated in a press release. "Anktiva has demonstrated strong disease control in CIS, and based on the latest data from our study, it is showing the same effect in papillary tumors. This gives us confidence in the potential for all BCG-unresponsive NMIBC patients to benefit from this combination therapeutic."

Overall, QUILT 3.032 is a multicenter, open-label, 3-cohort study. In cohorts A (CIS) and B (papillary) patients are treated with BCG plus N-803. Cohort C is enrolling patients with CIS and treating them with N-803 alone. While the primary end point of cohort B is DFS rate, the primary end point for cohorts A and C is the rate of complete response (CR).

At the time the results were reported, 73 patients had enrolled in cohort B. Previously reported results for cohort A included data for 81 patients. Results presented for cohort A during the 2021 American Urological Association Annual Meeting showed that BCG plus N-803 reached a CR rate of 72% and a 58.6% probability of maintaining a CR for at least 12 months.

 Additionally, at a median follow-up of 20.4 months, the median duration of CR was 19.9 months.

A combined safety analysis of cohorts A and B (n = 154) showed that there were no immune-related or treatment-related severe adverse events in any patients.

In December 2019, the FDA granted N-803 a Breakthrough Therapy Designation for use in combination with BCG in patients with BCG-unresponsive NMIBC and CIS.

ImmunityBio plans to share full efficacy and safety data for cohorts A and B at the ASCO GU Symposium in February 2022.

1. ImmunityBio Announces Primary Endpoint Met in a Second Indication in Bladder Cancer Trial with 57% Disease-Free Survival in Patients with BCG Unresponsive Papillary Disease. Published online October 19, 2021. Accessed October 20, 2021. https://yhoo.it/3pkHMwp.

2. Chamie K, Chang S, Gonzalgo M, et al. Phase 2/3 clinical results of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in-situ (CIS) patients (cohort A). Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract PD09-05

Data from the phase 2/3 QUILT-3.032 trial showed that adding N-803 to BCG met the primary end point of disease-free survival in patients with BCG-unresponsive, high-grade non–muscle-invasive bladder cancer and papillary disease.

IL-15 superagonist N-803 shows strong clinical activity in papillary NMIBC

Interim 1-year results from the pivotal ROBUST III trial showed that the novel Optilume urethral drug-coated balloon improved outcomes versus standard endoscopic management in patients with recurrent anterior urethral strictures.

Findings presented during the 2021 International Continence Society Annual Meeting showed the primary end point of anatomical success at 6 months was reached by 74.6% of patients in the Optilume arm versus 26.8% of patients in the standard of care arm.

According to presenting author Justin Chee, MBBS, FRACS, a reconstructive urologist at MURAC health in Melbourne, Australia, the study defined anatomical success as the “Ability to pass a 16F flexible cystoscope through the treated area without prior repeat intervention.”

Chee also reported that the time to treatment failure (

 <.0001) and the rate of freedom from repeat intervention (dilation, urethroplasty, or clean intermittent catheterization) through 1 year (

 <.0001) were also significantly higher in the Optilume arm.

Also, although immediate symptomatic improvement and immediate improvement in functional improvement of maximum flow rate were observed in both arms, these improvements were only sustained in the Optilume arm, while levels in the control arm returned to near baseline at 1 year.

“Optilume exhibited a significant improvement in [the primary] objective outcome at 6 months and subjective outcomes at 1-year post treatment compared to standard of care,” said Chee. “The novel drug-coated balloon may represent a breakthrough in the endoscopic management of recurrent anterior urethral stricture disease.”

The prospective, single-blind, multicenter ROBUST III trial was open to all patients with urethral strictures, although over 90% of patients had strictures located in the bulbar. Patients had to have strictures ≤3 cm, an IPSS >10, max voiding flow rates of <15 mls/s, and at least 2 prior dilations.

Baseline characteristics were similar in both arms with an average of 3.6 prior endoscopic treatments and an average stricture length of 1.7 cm.

The analysis Chee presented included data from 123 patients enrolled across 23 clinical sites in the United States and Canada.

Patients were randomized in a 2:1 ratio to Optilume (n = 79) or standard endoscopic management (n = 49). Stratification was done by prior radiation and number of dilations (less than 5 or greater than 5).

The standard endoscopic treatment assigned in the control arm was either a rod, uncoated balloon, or direct vision internal urethrotomy, depending on which approach was considered to be the best standard of care for the patient.

The trial was single blind, with subjects blinded to the 6-month primary end point. At the unblinding, patients in the control arm who met predetermined eligibility criteria were allowed to cross over to receive Optilume.

The investigators observed that outcomes consistently favored Optilume among subgroups with either ≥5 or <5 dilations, as well as subgroups with either a ≥2 cm or <2 cm stricture length.

The primary safety endpoint was freedom from these 3 severe adverse events at 3 months: the formation of a urethral fistula, de novo SUI not resolved by 3 months, and urethral rupture or burst.

Chee reported that there were no cases of these primary safety end points in either study arm.

He added that, “Adverse event rates were similar between arms with the exception of a trend toward more mild post-procedure dysuria and hematuria in the Optilume arm, which generally resolved within 30 days of treatment.”

In his concluding remarks, Chee said that going forward, “Follow-up through 5 years is planned to further define the durability of the treatment.”

1. Chee J, Elliott S, Virasoro R, et al. A randomized controlled trial evaluating the Optilume urethral drug coated balloon vs endoscopic management for treatment of recurrent anterior urethral strictures. Paper presented at: 2021 International Continence Society Annual Meeting; October 14-October 17; Melbourne, Australia. Abstract 2.

2. ROBUST III- Re-Establishing Flow Via Drug Coated Balloon For The Treatment Of Urethral Stricture Disease (ROBUST-III). NIH US National Library of Medicine: ClinicalTrials.gov. Posted April 17, 2018. https://clinicaltrials.gov/ct2/show/NCT03499964. Accessed September 23, 2020.

“Optilume exhibited a significant improvement in [the primary] objective outcome at 6 months and subjective outcomes at 1-year post treatment compared to standard of care,” said Justin Chee, MBBS, FRACS.

Optilume drug-coated balloon superior to standard care for recurrent anterior urethral strictures

The pivotal randomized cohort is fully enrolled in the phase 1b/2 EV-103 (KEYNOTE-869) trial assessing the first-line combination of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) in cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma.

In the cohort, known as cohort K, patients are being randomized to either monotherapy with the antibody-drug conjugate enfortumab vedotin or combination therapy with enfortumab vedotin plus the PD-1 inhibitor pembrolizumab.

“Completing enrollment in this study is an important step in investigating the potential for the combination of Padcev and Keytruda to treat metastatic urothelial cancer,” Roger Dansey, MD, chief medical officer, Seagen, which codevelops enfortumab vedotin with Astellas Pharma, stated in a press release. “If results of this study are compelling, we may have the opportunity to submit them to the FDA as part of an application for accelerated approval.”

Overall, the ongoing, multicohort, open-label, multicenter EV-103 trial (NCT03288545) is evaluating enfortumab vedotin alone and with different combinations of anticancer therapies as a first- and second-line treatment for patients with locally advanced or metastatic urothelial cancer.

Based on prior results from the EV-103 trial, the FDA granted a breakthrough therapy designation to enfortumab vedotin plus pembrolizumab (Keytruda) as a first-line treatment for patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy.

The designation, which will expedite the development and regulatory review of the combination in this setting, was based on findings from the dose-escalation and dose-expansion cohort A of the EV-103 trial,

 which enrolled patients with locally advanced or metastatic urothelial cancer who were not eligible for cisplatin-based chemotherapy.

The cohort included 45 patients, with a median age of 69 years. Men accounted for 80% (n = 36) of the study population and the primary tumor location was lower tract in 69% (n = 31) of patients. Sites of metastasis included lymph nodes only in 4 patients and visceral disease in the remaining 41 patients, including liver metastases in 15 patients. PD-L1 expression status by combined composite score was less than 10 in 19 patients, 10 or higher in 13 patients, and was not evaluable/available in 13 patients.

Results from this cohort showed that the combination led to an objective response rate (ORR) of 73%, comprising a 15.6% complete response rate and a 57.8% partial response rate.

“The FDA’s Breakthrough Therapy designation is based on preliminary data on the combination of Padcev and Keytruda,” Andrew Krivoshik, MD, PhD, senior vice president and head of Development Therapeutic Areas, Astellas, stated in the release. “Both Cohort K of EV-103 and our ongoing, broader phase 3 EV-302 study are evaluating this platinum-free combination in patients with previously untreated advanced urothelial cancers.”

1. Seagen and Astellas Complete Enrollment in EV-103 Trial Cohort K Combining PADCEV® (enfortumab vedotin-ejfv) With Pembrolizumab as First-Line Treatment for Advanced Urothelial Cancer. Published online October 12, 2021. Accessed October 13, 2021. https://bit.ly/3lCNKq6.

2. Rosenberg JE, Flaig TW, Friedlander TW, et al. Study EV-103: Preliminary durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma. 

“If results of this study are compelling, we may have the opportunity to submit them to the FDA as part of an application for accelerated approval," said Roger Dansey, MD.

Jason M. Broderick

Articles

Platelet-rich plasma injections safe and feasible treatment for Peyronie’s disease

IL-15 superagonist N-803 shows strong clinical activity in papillary NMIBC

Optilume drug-coated balloon superior to standard care for recurrent anterior urethral strictures

Key cohort fully enrolled in EV-103 pembrolizumab/enfortumab vedotin bladder cancer trial