Clinical Trials Corner

Dear Readers,

The Clinical Trials Corner of the Bladder Cancer journal is a section devoted towards highlighting ongoing trials or recently completed trials in urothelial cancer. Our hope is to encourage accrual for ongoing trials and to educate readers on the results of completed trials. If you feel that you would like to draw attention to a specific trial, please feel free to email us at: [email protected] and/or [email protected].

Sincerely,

Piyush K. Agarwal Cora N. Sternberg
Piyush K. Agarwal, MD Cora N. Sternberg, MD, FACP
Associate Editor, Bladder Cancer Associate Editor, Bladder Cancer
Director, Bladder Cancer Program Clinical Director, Englander Institute of Precision Medicine
University of Chicago Medicine Weill Cornell Medicine
Chicago, IL, USA New York, NY, USA

QUILT-3.032: A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-803) in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer (NMIBC)

Status: 
Completed
Clinicaltrials.gov identifier: 
NCT03022825
Sponsor: 
ImmunityBio, Inc.
Enrollment: 
171
Study Design: 
Phase II/III single arm, multi-center study of patients with BCG-unresponsive CIS with or without papillary (Ta/T1) NMIBC treated with intravesical NAI/N-803 (400 lg/instillation) plus BCG intravesical BCG (50 mg/ instillation) (cohort A) or without BCG (cohort C). Patients with BCG-unresponsive high-grade papillary (Ta/T1) NMIBC without CIS were also treated with intravesical NAI/N-803 plus BCG (cohort B). Patients had to be absent of resectable disease after TURBT procedures, and those with high-grade Ta and/or T1 disease had a complete resection before study treatment. Biopsy was required at week 12 (approximately 3 months).
Rationale: 
Some 80% of new bladder cancer diagnoses are non–muscle-invasive bladder cancer (NMIBC). BCG-unresponsive NMIBC is an increasingly interesting disease state for drug development in bladder cancer. Impaired T-cells and natural killer (NK) cells may contribute to BCG-unresponsiveness. The immune cell–activating interleukin-15 (IL-15) superagonist Nogapendekin alfa inbakicept (NAI), also known as N-803, can activate and proliferate NK cells and T-cells. Therefore, the hypothesis that the addition of N-803 to BCG could potentially enhance BCG efficacy was preliminarily tested in a small Phase I trial with limited toxicity and an impressive response rate. The current trial was a Phase II/III multicenter study to look at efficacy.
Endpoints: 
The primary endpoint was the incidence of a complete response (CR) at the 3- or 6-month assessment for cohorts A and C and the disease-free survival of cohort B at 12 months. Secondary endpoints include disease-specific survival, progression-free survival, overall survival, and avoidance of cystectomy.
Comments: 
There is considerable activity with the combination of N-803 and BCG in BCG-unresponsive NMIBC that leads to good response rates at 12 months and beyond and avoidance of cystectomy. The data are in line with expectations for novel therapies in this disease space. From this study, it emerges that the treatment is tolerable with a side effect profile that can be expected with intravesical therapy. However, the activity of N-803 as a single agent appears to be minimal. A subgroup that requires further careful observation is high-grade T1 tumors associated with CIS (HGT1/CIS), as these patients have the highest risk of progression. Only 9 patients were included in this trial. However, comparisons with other single-arm trials are always difficult in that there is substantial heterogeneity among BCG-unresponsive patient cohorts, and variation in the patient population and the quality of the TURBT among surgeons. For instance, development of UC of the prostatic urethra was not counted as treatment failure in this trial. In addition, a lower CR rate in female patients is an interesting observation, that has been seen in other trials. It will be interesting to see whether the combination is equally effective in the BCG-naïve high-risk NMIBC disease state.
Results: 
A total of 171 patients were enrolled with 84 patients in cohort A, 77 patients in cohort B, and 10 patients in cohort C. In cohort A, 82 patients were evaluable with at least 3-month follow-up. Overall, a CR at any time was seen in 71% of patients (45 patients with response to initial treatment and 13 patients with response to re-induction). The CR rate was 45% at 12 months and 33% at 18 months for patients in cohort A. Furthermore, progression-free survival at 24 months was 84.7%. In the 71% of patients with a CR, only 7% underwent a subsequent cystectomy. In cohort B, the 12-month DFS for 72 evaluable patients was 55.4% and the cystectomy rate among responders was also 7%. In Cohort C, a CR at 3 months was only achieved in 2 (20%) patients. Despite reinduction at 6 months, only one patient (10%) maintained a CR at 6 months. Treatment-related adverse events in cohorts A and B were grade I to 2 in 86%.

Abstract #23-5631 - CORE-001: Phase 2 Single Arm Study of CG0070 Combined with Pembrolizumab in Patients with Non-Muscle Invasive Bladder Cancer Unresponsive to Bacillus Calmette-Guerin (BCG)

Status: 
Completed
Clinicaltrials.gov identifier: 
NCT04387461
Sponsor: 
CG Oncology, Inc in collaboration with Merck
Study Design: 
Core-1 is a single arm phase II study. CG0070 was administered intravesically (IVE) weekly x 6. If the patient demonstrates persistent high-grade disease at Week 12, the patient will receive another cycle of 6 weekly treatments. If there is no disease present at Week 12 (e.g., CR) then the patient will receive 3 weekly treatments. Beginning at Week 24, patients will receive 3 weekly treatments every 3 months through Week 48 and then every 24 weeks thereafter. Pembrolizumab was administered intravenously every 3 weeks for up to 2 years and was started on day 1.
Rationale: 
Patients with BCG unresponsive disease have limited treatment options. Cretostimogene grenadenorepvec (CG0070) is a novel intravesical viral oncolytic therapy that has demonstrated efficacy in BCG unresponsive disease as a single agent. The addition of pembrolizumab may augment the immune response triggered by CG0070 and thereby, enhance efficacy. This trial evaluates the combination of CG0070 and pembrolizumab.
Endpoints: 
Complete response rate.
Comments: 
This small phase II study is encouraging and demonstrates higher CR rates than are seen with CG0070 or pembrolizumab alone. The current landscape of approved agents for BCG-unresponsive NMIBC may quickly expand beyond single agents to effective combination regimens. It is important to note that although the side effect profile was not any worse with combination therapy in this study, there are still rare, but potentially significant side effects that are possible with systemic therapies such as pembrolizumab.
Results: 
Using a data cut-off of March 3, 2023, 34 patients were evaluable for efficacy with a minimum of 3-months of follow up. At the initial 3-month timepoint, 29 of 34 (85%) patients achieved a CR. Of those patients evaluable for CR at additional timepoints, 82% (n=27/33) have also maintained a CR through 6 months, 81% (n=25/31) through 9 months and 68% (n=17/25) at the 12-month assessment. The combination of CG0070 and pembrolizumab has been well tolerated. The most common treatment-related AEs reported include transient grade 1-2 local genitourinary symptoms.

A Phase III Multicentre Randomised Controlled Trial to Compare the Efficacy of Robotically Assisted Radical Cystectomy (RARC) and Intracorporeal Urinary Diversion With Open Radical Cystectomy (ORC) in Patients With Bladder Cancer

Status: 
Completed
Clinicaltrials.gov identifier: 
NCT03049410
Sponsor: 
University College, London
Enrollment: 
339
Study Design: 
Prospective, multicenter randomized controlled trial randomizing patients undergoing radical cystectomy (1 : 1) to either intracorporeal robot-assisted radical cystectomy (iRARC) or open radical cystectomy (ORC) to assess recovery and morbidity.
Rationale: 
Although robot-assisted laparoscopic radical cystectomy with extracorporeal urinary diversion has been shown to be non-inferior to open radical cystectomy, it is unknown how a totally intracorporeal or robot-assisted laparoscopic urinary diversion will affect outcomes. Therefore, this trial compares intracorporeal robot-assisted radical cystectomy with radical cystectomy in terms of recovery and days in the hospital.
Endpoints: 
The primary endpoint was to compare the number of days alive and out of hospital within 90 days from surgery. The secondary endpoints were numerous and included: recovery, complications, quality of life, survival, disability, stamina, activity levels, and the return to normal activities.
Comments: 
There is a small statistically significant increase in days alive and out of the hospital with iRARC compared to open surgery. However, results may not be generalizable as the study was undertaken in high volume centers with surgeons with expertise in robotic surgery. In addition, the study took place during the COVID-19 pandemic and closed early so that may have affected some endpoints. It may be that in order for robotic surgery to be potentially better than open surgery, a totally intracorporeal approach may need to be employed.
Results: 
A total of 338 patients were randomized and 306 patients ultimately underwent radical cystectomy (157 had iRARC and 149 had ORC). Most patients had an ileal conduit diversion (89%). The median number of days alive and out of the hospital within 90 days of surgery was 82 (IQR: 76-84) for patients undergoing iRARC vs. 80 (IQR: 72-83) for patients undergoing ORC (adjusted difference, 2.2 days [95% CI, 0.50-3.85]; P = .01). Thromboembolic and wound complications were less common with robotic surgery than open surgery. There were no statistically significant differences in cancer recurrence and overall mortality at median follow-up of 18.4 months.

PHOTOdynamic versus white light-guided treatment of non-muscle invasive bladder cancer: randomised trial of clinical and cost-effectiveness

Status: 
Completed
Clinicaltrials.gov identifier: 
ISRCTN84013636
Sponsor: 
National Institute for Health and Care Research Health Technology Assessment and Newcastle upon Tyne NHS Trust
Study Design: 
Patients with NMIBC and intermediate or high risk of recurrence based on visual diagnosis were randomized (1 : 1) to PDD-TURBT or standard white light TURBT.
Rationale: 
Recurrence of non-muscle invasive bladder cancer (NMIBC) is common and the use of photodynamic diagnosis (PDD) at the time of TURBT (transurethral resection of bladder tumor) may assist in identification of tumors and may decrease recurrence of NMIBC over time. Therefore, this study aims to evaluate whether a PDD-assisted TURBT reduces the NMIBC recurrence rate compared to a standard white light (WL)-TURBT.
Endpoints: 
The primary endpoint was time to recurrence at 3 years of follow-up
Comments: 
The authors concluded that a PDD-TURBT did not reduce recurrences and was more expensive than WL-TURBT at 3 years. However, the recurrence rates appeared to clearly diverge over the first 12 months favoring PDD-TURBT. This may imply that the benefit of a single PDD-TURBT may only last for 12 months. Finally, the trial was designed to detect 214 recurrences but only 170 patients recurred so a smaller, clinically significant difference may exist but was not identified because so many patients were excluded from the analysis.
Results: 
A total of 538 patients were recruited (269 patients per group), but 112 patients were excluded due to no histologic diagnosis of NMIBC or having undergone a cystectomy. After a median follow-up of 44 months, 86 of 209 (41.1%) patients in the PDD group and 84 of 217 (38.7%) patients in the white light group had recurrences. Three-year recurrence rates were 57.8% (95% CI: 50.7-64.2) and 61.6% (95% CI: 54.7-67.8) in the PDD and WL groups, respectively. There was no difference in adverse events or health-related quality of life. PDD-TURBT was 876 pounds (95% CI: -766-2518, P = 0.591) more costly than WL-TURBT over a 3-year follow-up period. Immediate postoperative intravesical Mitomycin C was administered in 63.2% of the PDD group and 65.9% of the WL group (p = 0.60).

Study EV-103 Cohort K: Antitumor activity of enfortumab vedotin (EV) monotherapy or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC)

Status: 
Completed
Clinicaltrials.gov identifier: 
NCT03288545
Sponsor: 
Seagen Inc., Astellas Pharma, Merck & Co., Inc.
Enrollment: 
149
Study Design: 
Cohort K of this trial included untreated cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer were randomized 1 : 1 to either EV monotherapy (1.25 mg/kg) on days 1 and 8 or in combination with pembrolizumab (200 mg) on day 1 of 3-week cycles.
Rationale: 
The current first-line standard of care for locally advanced or metastatic urothelial carcinoma is cisplatin-based combination chemotherapy. However, cisplatin-ineligibility limits first-line treatment options. This trial explores the efficacy of enfortumab vedotin (EV) in the first-line setting for cisplatin-ineligible patients with and without pembrolizumab as they both have shown benefit independently in the second-line and later settings. EV is an antibody-drug conjugate. It is a nectin-4-directed antibody and microtubule inhibitor conjugate. Pembrolizumab is an anti-PD-1 monoclonal antibody approved in the treatment of urothelial cancer after chemotherapy or in platinum ineligible patients who express PDL-1.
Endpoints: 
The primary endpoint was confirmed objective response rate (ORR) per RECIST v1.1 by BICR (blinded independent central review). Secondary endpoints included duration of response (DOR) and safety (treatment-related adverse events, TRAEs). There were no formal statistical comparisons between treatment arms.
Comments: 
There are limited options for first line therapy for cisplatin-ineligible metastatic urothelial cancer patients. This trial not only reaffirms the benefit of EV monotherapy but also demonstrates safety and efficacy with the combination of EV and pembrolizumab, that could become a new standard of care.
Results: 
A total of 149 patients, 73 in the EV arm and 76 in the combination arm, were enrolled and treated. Confirmed ORR for the EV arm was 45.2% (95% CI: 33.5-57.3) and median DOR was 13.2 months (95% CI: 6.1-16.0). Confirmed ORR for the combination arm was 64.5% (95% CI: 52.7-75.1) and median DOR was not yet reached. TRAEs occurred more commonly in the combination arm compared to the monotherapy arm and included: skin reactions (67.1% vs. 45.2%, respectively) and peripheral neuropathy (60.5% vs. 54.8%, respectively). Lesser TRAEs include ocular disorders and hyperglycemia.

Abraxane With Anti-PD1/PDL1 in Patients With Advanced Urothelial Cancer (ABLE)

Status: 
Completed
Clinicaltrials.gov identifier: 
NCT03240016
Sponsor: 
University of Michigan Rogel Cancer Center
Enrollment: 
36
Study Design: 
This is a single arm, single center, phase II study of nab-paclitaxel and pembrolizumab in patients with platinum-refractory or cisplatin-ineligible advanced urothelial carcinoma. Eligible patients had RECIST 1.1 measurable disease. Patients were treated with nab-paclitaxel 125 mg/m2 IV on days 1 and 8 and pembrolizumab IV 200 mg in 21-day cycles Nab-paclitaxel could be discontinued after 6 cycles.
Rationale: 
The current first-line standard of care for locally advanced or metastatic urothelial carcinoma is cisplatin-based combination chemotherapy. Despite responses in 50%-70% of patients in the first line setting, most eventually progress and median overall survival is about 14 months. For cisplatin ineligible patients OS is even worse, around 9 months. Cisplatin-ineligibility or unresponsiveness to cisplatin presents a treatment challenge for patients. Pembrolizumab is an anti-PD-1 monoclonal antibody approved in the treatment of urothelial cancer after chemotherapy or in platinum ineligible patients who express PDL-1. Nanoparticle albumin-bound paclitaxel (Nab-paclitaxel; abraxane) does not require pre-medication and is also effective in platinum-refractory advanced urothelial carcinomas. This study evaluates the combination of pembrolizumab and nab-paclitaxel in patients with advanced urothelial carcinoma who are platinum-refractory or cisplatin-ineligible.
Endpoints: 
The primary endpoint was overall response rate (ORR). Secondary endpoints include: duration of response, safety/toxicity, progression-free survival, and overall survival.
Comments: 
In the Keynote 045 trial, after which pembrolizumab was registered as second line therapy, the median OS was 10.1 months in the pembrolizumab arm and superior to OS with chemotherapy. In the Keynote 052 trial of patients who were platinum ineligible, median OS with pembrolizumab was 11.3 months. In a phase II trial of Nab-paclitaxel median overall survival was 9.8 months. As it is always difficult to compare among trials, a median OS of 18.2 months in platinum refractory or cisplatin-ineligible patients with this combination is certainly promising and hypothesis generating. A phase III randomized trial of the combinaton versus Pembrolizumab is warranted.
Results: 
Overall 36 patients were enrolled onto the study. There was an equal number of platinum-refractory and cisplatin-ineligible patients. The ORR was 50% (18/36) and tumor shrinkage was confirmed in 31 of 36 patients. Confirmed overall response rate was 50.0% (18/36) including 3 complete and 15 partial responses; 31/36 patients experienced some tumor shrinkage. At a median follow-up of 19.7 months, the median duration of response was 4.4 months. Median PFS and OS were 6.8 months and 18.2 months, respectively. Of note, grade 3 or greater adverse events were noted in 21 of 36 patients. The combination was effective in patients refractory to or ineligible for cisplatin based chemotherapy albeit with some toxicity.

Extended Follow-up in Patients with Muscle-Invasive Bladder Cancer in the Checkmate 274 trial (An Investigational Immuno-therapy Study of Nivolumab, Compared to Placebo, in Patients With Bladder or Upper Urinary Tract Cancer, Following Surgery to Remove t

Status: 
Completed
Clinicaltrials.gov identifier: 
NCT02632409
Sponsor: 
Bristol-Myers Squibb
Enrollment: 
709
Study Design: 
This was an international, randomized, double-blind phase III trial. The original study randomized patients between IV nivolumab (NIVO) Q 2 weeks and IV placebo (PBO) Q 2 weeks after surgery. Patients were high-risk MIUC; if ypT2-ypT4a or ypN+, received neoadjuvant cisplatin CT; if pT3-pT4a or pN+, or did not receive neoadjuvant cisplatin CT and were ineligible for or refused adjuvant cisplatin CT. Patients underwent radical surgery within 120 days and were disease free within 4 weeks of study dosing.
Rationale: 
Based on the previous Checkmate 274 trial, adjuvant nivolumab for 1 year has become the standard of therapy after radical surgery for patients with muscle invasive urothelial cancer (MIUC) due to improvement in disease-free survival. This presentation at the AUA 2023 was on the extended follow-up of the muscle invasive bladder cancer cohort (MIBC) with a median follow-up of 3 years.
Endpoints: 
The primary endpoint was disease-free survival (DFS) in the ITT population and DFS in all randomized patients with PD-L1 ≥ 1%.The secondary endpoints were distant metastasis-free survival and non-urothelial tract recurrence-free survival (RFS).
Comments: 
Only approximately 40% of patients in this study received prior neoadjuvant chemotherapy. From the original presentation, it appeared that the HRs overlapped 1 for patients with upper tract tumors and more benefit was seen in the cohort with MIBC. With extended 3-year median follow-up, continued improvement in DFS was maintained. Although, overall survival data have still not been presented, this study is practice changing.
Results: 
Of 709 randomized pts, 560 had MIBC (NIVO, n=279; PBO, n=281). DFS was improved with NIVO vs PBO in all pts with MIBC (HR 0.63), and in the PD-L1 ≥1% (HR 0.44) and PD-L1 <1% (HR 0.74) subgroups. HR favored NIVO vs PBO for non-urothelial tract recurrence-free survival (HR 0.64) and distant metastasis-free survival (HR 0.70). Grade 3–4 treatment-related adverse events occurred in 17.3% and 5.8% of NIVO and PBO pts, respectively. In this study, there was a continued benefit in DFS, distant-metastasis-free survival, and RFS in both the ITT and muscle-invasive bladder cancer populations. Of note, all patients with PD-L1 greater than or equal to 1%, experienced a benefit in DFS. However, even MIBC with PD-L1 less than 1% still saw a benefit in DFS with nivolumab.

Intravesical Photodynamic Therapy (“PDT”) in BCG-Unresponsive/Intolerant Non-Muscle Invasive Bladder Cancer (“NMIBC”) Patients

Status: 
Completed
Clinicaltrials.gov identifier: 
NCT03945162
Sponsor: 
Theralase Technologies Inc.
Enrollment: 
57
Study Design: 
This is a phase II, open-label, single-arm, multi-center study conducted in Canada, the United States and internationally. Patients with NMIBC CIS with or without resected papillary disease (Ta, T1) that are considered bacillus Calmette-Guerin (BCG)-Unresponsive or who are intolerant to BCG therapy are included. The patients are treated with two photodynamic therapy treatments with TLD-1433 (a photosensitizer that specifically targets transferrin) at 0 and 180 days upon enrollment. The photosensitizer is instilled in the bladder and then activated with an intravesical laser. The interim results of the trial are reported at this meeting.
Rationale: 
This study evaluates a novel targeted form of photodynamic therapy in patients with BCG unresponsive CIS with or without papillary disease. The photosensitizer is instilled in the bladder and then activated by an intravesical laser.
Endpoints: 
The primary endpoint is complete response (CR) rate and the main secondary endpoint is duration of CR.
Comments: 
Photodynamic therapy has been proven to be effective in the past but was often plagued by side effects. The SAEs seen on this trial were not deemed to be due to the therapy and the historical concerns of bladder damage and sunlight sensitivity seen with older photodynamic therapy agents were not seen in this interim trial.
Results: 
The primary outcome was a 54% CR rate at any time. However, of the 12 patients who were evaluated at 450 days, 67% had a CR. There were 9 serious adverse events (SAEs) but none were deemed to be due to the photodynamic therapy

A Study of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With Non-Muscle Invasive Bladder Cancer (NMIBC)...

Status: 
Completed
Clinicaltrials.gov identifier: 
NCT04640623
Sponsor: 
Janssen Research & Development, LLC
Study Design: 
Phase 2b, multi-center study randomizing BCG-unresponsive high risk non-muscle invasive bladder cancer with CIS with or without papillary disease randomized 2:1:1 (by presence or absence of papillary disease) to TAR-200 + cetrelimab, TAR-200 alone, or cetrelimab alone.
Rationale: 
Patients with BCG unresponsive disease have limited treatment options. They may respond to the sustained release of gemcitabine through the use of a novel intravesical delivery system, TAR-200, either alone or in combination with a PD-1 antibody, cetrelimab. In addition, the trial evaluates the effect of cetrelimab alone as well.
Endpoints: 
The primary endpoint was complete response (CR) rate. The secondary endpoints were duration of response, overall survival, pharmacokinetics, and safety/tolerability.
Comments: 
The cetrelimab alone response rates are in line with what has been seen with pembrolizumab alone. However, TAR-200 responses were impressive and higher than seen with gemcitabine dosed in a usual intravesical fashion. However, toxicity was worse but consisted of local symptoms that are grade 1-2 in nature.
Results: 
The data from the two monotherapy arms was presented from a planned interim analysis. Seventy-three (73%) of patients in the TAR-200 arm achieved a CR while the CR rate was 38% in the cetrelimab arm. Grade greater than or equal to 3 adverse events (AEs) in TAR-200 group was 30% compared to 8% in the cetrelimab group. Of note, 15 of the 16 CRs in the TAR-200 group were still ongoing at the median follow-up of 11 months.

An Open-Label, Multi-Centre, Safety Study of Fixed-Dose Durvalumab in Advanced Solid Malignancies (STRONG Study).

Status: 
Open
Clinicaltrials.gov identifier: 
NCT03084471
Sponsor: 
AstraZeneca
Enrollment: 
867
Study Design: 
867 patients with urothelial or non-urothelial urinary tract carcinoma (UTC) who progressed during or after one platinum or non-platinum chemotherapy regimen were treated with fixed dose durvalumab (1500 mg every four weeks) to progressive disease. Thirteen percent of patients had an ECOG performance status (PS) of 2, but most had an ECOG PS of 0-1.
Rationale: 
Checkpoint inhibition has demonstrable activity in patients with locally advanced or metastatic urothelial carcinoma refractory to platinum chemotherapy. Durvalumab has previously demonstrated safety and efficacy in patients at 10 mg/kg dosed every 2 weeks. This trial evaluates a fixed dose of 1500 mg given every 4 weeks, a more convenient dosing schedule. Furthermore, it does so in a “real-world” clinical setting as patients could have non-urothelial histology and could have progressed or not responded to platinum or non-platinum chemotherapy.
Endpoints: 
The primary end-point was the incidence of adverse events of special interest (AESIs), including immune-mediated AEs (imAEs). Secondary end-points included overall survival (OS), objective response rate (ORR), and disease control rate (at six and 12 months) (DCR).
Comments: 
Durvalumab at a fixed dose was well tolerated. Of note, PD-L1 expression was available in 577 patients and tumor expression of PD-L1 was high in 239 (41%). Despite this finding, median OS was only 7 months in this fixed dose study compared to a previous study of durvalumab (study 1108) showing a median OS of 11 months. This is felt to be due to the “all-comers” status of this current trial with 13% of patients having ECOG PS of 2 and patients with nonurothelial histology. Although Durvalumab had attained Accelerated Approval by the FDA in urothelial cancer, failure of the DANUBE study in the first line setting, caused the company to voluntarily withdraw durvalumab from the US market. The data is nonetheless encouraging in the STRONG study that revealed durable clinical activity in previously chemotherapy-treated patients with advanced urothelial or nonurothelial urinary tract carcinoma.
Results: 
Median treatment duration was 12.1 weeks and 31% were alive and being followed for survival. The median follow-up for patients was 13.8 months. AEs of any grade occurred in 787 patients (91%) with the most common being asthenia (27%), constipation (20%), and anemia (21%). AESIs of any grade occurred in 51% of patients (8% grade ≥ 3). The incidence of imAEs was 11% (2% grade ≥ 3). The median OS was 7.0 months (95% confidence interval [CI]: 6.4–8.2) and ORR was 18% (95% CI: 14.8–20.6), with complete responses in 5% of patients and a disease control rate at six months of 19% (95% CI: 16.1–22.1).

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