Abstract
PURPOSE
Standard of care for muscle-invasive bladder cancer (MIBC) is radical cystectomy (RC) with neoadjuvant cisplatin-based chemotherapy (NAC). However, many patients are ineligible for or refuse cisplatin. SunRISe-4 (ClinicalTrials.gov identifier: NCT04919512) is an open-label, multicenter, parallel-cohort phase II study assessing neoadjuvant gemcitabine intravesical system (TAR-200/gem-iDRS) plus cetrelimab or cetrelimab monotherapy in patients with MIBC.
METHODS
Adults with Eastern Cooperative Oncology Group performance status 0-1, cT2-T4a N0M0, ineligible/refusing NAC, and planned for RC were randomly assigned 5:3, stratified by transurethral resection of bladder tumor completeness (residual tumor ≤3 cm permitted) and T stage, to receive TAR-200 plus cetrelimab (cohort 1) or cetrelimab monotherapy (cohort 2). The primary end point was pathologic complete response (pCR) at RC. Secondary end points included recurrence-free survival (RFS) and safety. Exploratory end points included pathologic overall response (pOR; ≤ypT1N0) and circulating tumor (ct) and urinary tumor (ut) DNA molecular residual disease (MRD). Side-by-side descriptive efficacy summary was planned.
RESULTS
At the May 9, 2025, data cutoff, 159 patients were treated; 88 in cohort 1 and 46 in cohort 2 underwent RC. pCR, pOR, and 1-year RFS rates were 38%, 53%, and 77% in cohort 1 and 28%, 44%, and 64% in cohort 2, respectively. pCR rates were consistent across subgroups. No new safety signals were observed. Across cohorts, utDNA– status before RC (week 12) and utDNA clearance correlated with pCR (P < 10–5 and < 10–3, respectively). ctDNA– status at baseline and week 12 was associated with longer RFS compared with ctDNA+ status at the same time point (P = .04 and 0.01, respectively).
CONCLUSION
TAR-200 plus cetrelimab provided higher pCR, pOR, and 1-year RFS rates compared with cetrelimab monotherapy, supporting further investigation of the neoadjuvant combination in MIBC. utDNA and ctDNA MRD results support further investigation as biomarkers for residual local and nonlocal disease, respectively.
INTRODUCTION
Standard of care for muscle-invasive bladder cancer (MIBC; cT2-T4a N0M0) is radical cystectomy (RC) with neoadjuvant cisplatin-based chemotherapy (NAC).1,2 Systemic gemcitabine and cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in this setting have been associated with pathologic complete response (pCR) rates in prospective trials of 26%-36%3-5 and 38%-42%,3,6,7 respectively. Recent data from a registrational trial demonstrated that the combination of durvalumab, a PD-L1 inhibitor, with neoadjuvant GC had a pCR rate of 37%.5
CONTEXT
Key Objective
To determine the contribution of the addition of gemcitabine intravesical system (TAR-200) to the efficacy and safety of an immune checkpoint inhibitor (cetrelimab) as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or refusing neoadjuvant cisplatin-based chemotherapy (NAC).
Knowledge Generated
TAR-200 plus cetrelimab showed high pathologic complete response, pathologic overall response, and 1-year recurrence-free survival rates, supporting a role for the combination in patients with MIBC planned for radical cystectomy and ineligible for or refusing NAC.
Relevance (J.W. Friedberg)
These results pave the way for definitive randomized trials in the neoadjuvant setting for patients with MIBC, and, if validated, demonstrate the role of urinary tumor DNA and circulating tumor DNA as a predictive biomarker.*
*Relevance section written by JCO Editor-in-Chief Jonathan W. Friedberg, MD.
Despite efficacy, NAC is associated with significant toxicity in this predominantly older, medically complex population, with grade ≥3 adverse events (AEs) occurring in 18%-44% of patients with MIBC treated with neoadjuvant GC8,9 and 32%-55% treated with neoadjuvant MVAC.8,10 Furthermore, many patients with MIBC refuse NAC, and as many as half are cisplatin-ineligible according to consensus criteria, frequently because of insufficient kidney function.11-14 Notably, pCR rates are low (12%-15%) in patients with MIBC who undergo RC without neoadjuvant therapy.6,15,16 Thus, there is an unmet medical need for neoadjuvant therapy options for patients with MIBC who are ineligible for or refuse NAC.
Gemcitabine intravesical system (TAR-200/gem-iDRS) is a novel intravesical drug-releasing system designed to provide sustained delivery of gemcitabine within the bladder.17 TAR-200 monotherapy is approved in the United States to treat patients with Bacillus Calmette-Guérin-unresponsive high-risk non-MIBC carcinoma in situ with or without papillary disease, on the basis of results of the phase IIb SunRISe-1 study.18,19 Clinical activity for TAR-200 was observed in patients with MIBC in phase I studies.20,21 Cetrelimab is a monoclonal antibody inhibitor of PD-1.22,23 In clinical trials, neoadjuvant treatment with immune checkpoint inhibitor monotherapy has shown clinical activity in patients with MIBC (pCR rates, 31%-37%).24-26 Neoadjuvant treatment with the combination of TAR-200 and cetrelimab may improve pCR rates and long-term oncologic outcomes in patients with MIBC, while reducing toxicities associated with systemic chemotherapy regimens.
SunRISe-4 (ClinicalTrials.gov identifier: NCT04919512) is an open-label, multicenter, parallel cohort, randomized phase II study assessing neoadjuvant TAR-200 plus cetrelimab or cetrelimab monotherapy in patients with MIBC scheduled for RC and who are ineligible for or refuse NAC. Here, we report efficacy, safety, and exploratory biomarker outcomes from the primary analysis of SunRISe-4.
METHODS
Study Oversight
The study protocol was designed by the sponsor, Johnson & Johnson. SunRISe-4 was conducted in accordance with current Good Clinical Practice guidelines of the International Council for Harmonisation, applicable regulatory and country-specific requirements, and principles of the Declaration of Helsinki, and was approved by review boards at all participating institutions. All patients provided written informed consent.
An independent data-monitoring committee was commissioned by the sponsor to review safety and efficacy data and make recommendations regarding study conduct. Data captured by site personnel in case report forms were transcribed in a sponsor database system.
Patients
Eligible patients were age ≥18 years, had Eastern Cooperative Oncology Group performance status 0 or 1, had histologically confirmed cT2-T4a MIBC (minor histologic variants permitted) with absence of nodal or metastatic disease at screening, were ineligible for or refused NAC, and were planned for RC. Cisplatin ineligibility was defined by Galsky criteria: glomerular filtration rate <60 mL/min/1.73 m2, grade ≥2 (Common Terminology Criteria for Adverse Events version 5.0 [CTCAE v5.0] audiometric hearing loss, and/or CTCAE v5.0 grade ≥2 peripheral neuropathy).11,12 Residual intravesical tumors of ≤3 cm after transurethral resection of bladder tumor (TURBT) were permitted. Key eligibility criteria are described in the Data Supplement (online only).
Study Design and Treatment
The phase II, open-label, parallel cohort SunRISe-4 study (Data Supplement, Fig S1) was designed for each cohort to be assessed independently.
Patients were randomly assigned 5:3 to receive TAR-200 plus cetrelimab (cohort 1) or cetrelimab monotherapy (cohort 2). Patients were stratified on the basis of completeness of TURBT (visibly complete vs incomplete ≤3 cm) and tumor stage (cT2 v cT3-4a) at initial MIBC diagnosis.
In cohort 1, patients underwent TAR-200 (225 mg gemcitabine) placement once every 3 weeks through week 12 (four consecutive cycles) as an outpatient procedure. TAR-200 was removed via cystoscopy in an outpatient procedure, and upon removal, a new TAR-200 was placed during the same visit. The final TAR-200 was removed in the clinic or at the time of RC. In cohorts 1 and 2, intravenous cetrelimab (360 mg) dosing was once every 3 weeks for 12 weeks (four consecutive cycles). If occurring on the same day as a TAR-200 placement, cetrelimab administration was completed 45 minutes or more before or after TAR-200 placement.
Patients underwent RC at week 12, within a protocol-specified window of 11-15 weeks.
End Points
The primary end point was the pCR rate, defined as the percentage of patients with pCR (ypT0N0) on RC specimen. The results for pCR were derived from the analysis of the RC bladder specimen based on central blinded histopathologic review.
Key secondary end points included recurrence-free survival (RFS) and safety. RFS was defined as the time from first dose of any study treatment to first radiologic evidence of nodal or metastatic disease that precludes RC, first radiologic evidence of nodal or metastatic disease after RC, or death due to any cause. Safety was assessed by the number of patients with AEs by grade (CTCAE v5.0 grades) and the number of patients with laboratory abnormalities (defined by CTCAE v5.0 grades using change from baseline to worst postbaseline value). Pathologic overall response (pOR) rate was an exploratory end point (pOR defined as downstaging to ≤ypT1N0).
Exploratory biomarker analysis examined PD-L1 status (clone SP263 [Roche]; LabCorp, Los Angeles, CA) in addition to detection of circulating tumor DNA (ctDNA; Natera Signatera; Natera, Inc, Austin, TX) and urinary tumor DNA (utDNA; UROAmp assay; Convergent Genomics, South San Francisco, CA)27 to determine the presence or absence of molecular residual disease (MRD). Blood and urine samples for biomarker analysis were collected at baseline and week 12 (before RC).
Assessments
Diagnostic TURBT samples underwent pathologic review by the study site and were confirmed by central review. If the screening cystoscopy showed residual tumors >3 cm, a repeat TURBT was performed before random assignment.
Clinical follow-up visits and laboratory tests, including urine culture, occurred every 4 weeks through week 12 post-RC and every 12 weeks thereafter. Cross-sectional imaging (computed tomography/magnetic resonance imaging of the chest, abdomen, and pelvis) was performed at week 6 of treatment and then every 12 weeks post-RC. If metastatic progression was observed (confirmed by blinded central radiology review), the patient was discontinued from efficacy follow-up. If signs and symptoms indicated local progression, the patient was discontinued from treatment and underwent RC immediately. Safety follow-up continued until 100 days after receipt of the last study treatment. Survival follow-up continued until death, withdrawal of study consent, or week 108 post-RC. Patients with an in-dwelling TAR-200 at the time of study withdrawal were required to undergo TAR-200 removal at the study site.
Biomarker assessments are described in the Data Supplement.
Statistical Analysis
The primary analysis was planned for approximately 6 months after 160 patients had been treated. Two prespecified interim analyses were conducted. The results of the second interim analysis were reported previously.28 Here, we report the results of the primary analysis.
A side-by-side descriptive summary of efficacy was planned to assess the contribution of TAR-200 efficacy as part of the combination. No formal statistical hypotheses were tested to compare cohorts. Summary statistics (frequency counts, percentages, and 95% CIs) are reported; 95% CIs were calculated using the Clopper-Pearson method.29 RFS distribution was estimated using the Kaplan-Meier method. Patients without RFS events were censored at the last study disease assessment.
Two populations were analyzed: (1) The efficacy-evaluable set included all patients who underwent RC with results from central, blinded histopathology review; (2) the full analysis set included all patients who received ≥1 dose of study treatment.
Additional statistical methods are in the Data Supplement, including statistical hypotheses, sample size determination, and exploratory biomarker analysis.
RESULTS
Study Disposition and Treatment
Beginning July 2022, 252 patients were screened for eligibility, 163 were enrolled across 64 sites in three regions, 104 were randomly assigned to receive TAR-200 plus cetrelimab (cohort 1), and 59 were randomly assigned to receive cetrelimab monotherapy (cohort 2; Fig 1). As of the May 9, 2025, data cutoff, 159 patients have received study treatment (full analysis set), 101 in cohort 1 and 58 in cohort 2 (treatment exposure in the Data Supplement). The median duration of follow-up was 14.1 months (range, 1.2-32).
FIG 1.
CONSORT diagram for patient enrollment, treatment, and disposition in SunRISe-4.
Of the 159 treated patients, 134 (84.3%) underwent RC (efficacy-evaluable set) including 114 of 134 (85.1%) who had surgery on schedule at week 12 (within the protocol-specified window of weeks 11-15). The median time to RC was 13.4 weeks (range, 2.6-19.4). Nine patients (6.7%) underwent RC before and 11 (8.2%) after the protocol-specified window (reasons for early RC or delayed RC are listed in the Data Supplement, Table S1).
Patient Demographics and Baseline Characteristics
Across both cohorts, the median age was 73 years; most patients were male (83.0%) and White (72.3%) with visibly complete TURBT (83.0%) and without variant histology (76.1%; Table 1). Ninety-one patients (57.2%) had refused NAC, most frequently because of quality-of-life concerns (41.5%). Sixty-eight patients (42.8%) were cisplatin-ineligible, most frequently because of insufficient kidney function (27.7%).
TABLE 1.
Demographics and Disease Characteristics at Baseline in Patients With MIBC Treated With Neoadjuvant TAR-200 Plus Cetrelimab (cohort 1) or Cetrelimab Monotherapy (cohort 2)
| Characteristic | Cohort 1: TAR-200 Plus Cetrelimab (n = 101) | Cohort 2: Cetrelimab Monotherapy (n = 58) |
|---|---|---|
| Age, years, median (IQR) | 74 (69-77) | 69 (64-74) |
| Sex, male, No. (%) | 86 (85.1) | 46 (79.3) |
| Race, No. (%) | ||
| White | 72 (71.3) | 43 (74.1) |
| Asian | 18 (17.8) | 11 (19.0) |
| Other | 11 (10.9) | 4 (6.9) |
| Geographic region, No. (%)a | ||
| America | 40 (39.6) | 21 (36.2) |
| Asia | 20 (19.8) | 12 (20.7) |
| Western Europe | 41 (40.6) | 25 (43.1) |
| Nicotine use, No. (%) | ||
| Current | 26 (25.7) | 12 (20.7) |
| Former | 51 (50.5) | 34 (58.6) |
| Never | 1 (1.0) | 0 |
| Unknown | 23 (22.8) | 12 (20.7) |
| ECOG performance status, No. (%) | ||
| 0 | 83 (82.2) | 45 (77.6) |
| 1 | 18 (17.8) | 13 (22.4) |
| Tumor stage at initial diagnosis, No. (%) | ||
| T2 | 79 (78.2) | 49 (84.5) |
| T3 | 19 (18.8) | 8 (13.8) |
| T4a | 3 (3.0) | 1 (1.7) |
| Prior intravesical therapy, No. (%) | 12 (11.9) | 9 (15.5) |
| Residual disease (visibly incomplete TURBT), No. (%) | 19 (18.8) | 8 (13.8) |
| PD-L1 status, No. (%)b | ||
| Low | 33 (50.8) | 23 (74.2) |
| High | 32 (49.2) | 8 (25.8) |
| Urothelial carcinoma with variant histology, No. (%) | 22 (21.8) | 16 (27.6) |
| Reason for not receiving neoadjuvant cisplatin-based chemotherapy, No. (%) | ||
| Ineligible | 46 (45.5) | 22 (37.9) |
| Glomerular filtration rate <60 mL/min | 29 (28.7) | 15 (25.9) |
| Grade ≥2 audiometric hearing loss | 11 (10.9) | 3 (5.2) |
| Grade ≥2 peripheral neuropathy | 4 (4.0) | 3 (5.2) |
| Multiple | 2 (2.0) | 1 (1.7) |
| Refused | 55 (54.5) | 36 (62.1) |
| Quality of life | 34 (33.7) | 32 (55.2) |
| Age | 10 (9.9) | 2 (3.4) |
| Patient comorbidity | 3 (3.0) | 1 (1.7) |
| Patient decision | 6 (5.9) | 1 (1.7) |
| Other | 2 (2.0) | 0 |
Abbreviations: ECOG, Eastern Cooperative Oncology Group; MIBC, muscle-invasive bladder cancer; TURBT, transurethral resection of bladder tumor.
America includes the United States; Asia includes Israel and South Korea; Western Europe includes Belgium, France, Germany, Italy, the Netherlands, Poland, Spain, and the United Kingdom.
Percentages are based on number of patients with available PD-L1 status data. n = 65 patients with available data in cohort 1; n = 31 patients with available data in cohort 2.
Efficacy
The centrally reviewed pCR rates at RC (efficacy-evaluable set) were 37.5% (95% CI, 27.4 to 48.5) in patients treated with neoadjuvant TAR-200 plus cetrelimab and 28.3% (95% CI, 16.0 to 43.5) in patients who received cetrelimab monotherapy (Table 2). The pOR rates were 53.4% (95% CI, 42.5 to 64.1) and 43.5% (95% CI, 28.9 to 58.9) in the TAR-200 plus cetrelimab and cetrelimab monotherapy cohorts, respectively. Concordance between local and central, blinded review was high, with agreement in histopathology results in samples from 126 of 134 patients (94.0%; Data Supplement, Table S2). In both cohorts, centrally reviewed pCR and pOR rates were generally consistent across clinically relevant subgroups, including tumor stage and residual disease (visibly complete v visibly incomplete TURBT; Data Supplement, Figs S2 and S3).
TABLE 2.
Pathologic Response Rates in Patients With MIBC Treated With Neoadjuvant TAR-200 Plus Cetrelimab (cohort 1) or Cetrelimab Monotherapy (cohort 2)
| Pathologic Response | Cohort 1: TAR-200 Plus Cetrelimab (n = 88), % (95% CI) | Cohort 2: Cetrelimab Monotherapy (n = 46), % (95% CI) |
|---|---|---|
| Central blinded review (primary end point) | ||
| pCR | 37.5 (27.4 to 48.5) [n = 33] | 28.3 (16.0 to 43.5) [n = 13] |
| pOR | 53.4 (42.5 to 64.1) [n = 47] | 43.5 (28.9 to 58.9) [n = 20] |
| Local review | ||
| pCR | 36.4 (26.4 to 47.3) [n = 32] | 30.4 (17.7 to 45.8) [n = 14] |
| pOR | 55.7 (44.7 to 66.3) [n = 49] | 43.5 (28.9 to 58.9) [n = 20] |
Abbreviations: MIBC, muscle-invasive bladder cancer; pCR, pathologic complete response; pOR, pathologic overall response.
Consistent pCR and pOR rates were observed in sensitivity analyses that included patients with centrally reviewed RC or radiographic progression or death before RC and all patients who received study treatment (full analysis set; Data Supplement, Table S3).
Median RFS was not reached in either cohort (Fig 2). The 12-month RFS rate was 77.4% (95% CI, 66.6 to 85.1) in the TAR-200 plus cetrelimab cohort and 64.1% (95% CI, 47.3 to 76.8) in the cetrelimab monotherapy cohort.
FIG 2.
Recurrence-free survival (Kaplan-Meier curve) in patients with MIBC treated with neoadjuvant TAR-200 plus cetrelimab (cohort 1) or cetrelimab monotherapy (cohort 2). MIBC, muscle-invasive bladder cancer.
Safety
The most frequent AEs (≥25% of patients), including both AEs related to study treatment and those unrelated to study treatment, were dysuria (37.6%), pollakiuria (32.7%), anemia (30.7%), urinary tract infection (28.7%), and constipation (25.7%) in the TAR-200 plus cetrelimab cohort and urinary tract infection (25.9%) in the cetrelimab monotherapy cohort (Data Supplement, Table S4). The most frequent treatment-related AEs (TRAEs) in patients who received TAR-200 plus cetrelimab were dysuria (30.7%), pollakiuria (30.7%), and micturition urgency (17.8%; Table 3). The most frequent TRAEs with cetrelimab monotherapy were fatigue (12.1%) and pruritus (12.1%).
TABLE 3.
Summary of TRAEs in Patients With MIBC Treated With Neoadjuvant TAR-200 Plus Cetrelimab (cohort 1) or Cetrelimab Monotherapy (cohort 2)
| Patients With ≥1 Event | Cohort 1: TAR-200 Plus Cetrelimab (n = 101), No. (%) | Cohort 2: Cetrelimab Monotherapy (n = 58), No. (%) | ||
|---|---|---|---|---|
| Any Grade | Grade ≥3 | Any Grade | Grade ≥3 | |
| Any TRAEa,b | 82 (81.2) | 16 (15.8) | 30 (51.7) | 6 (10.3) |
| Dysuria | 31 (30.7) | 0 | 1 (1.7) | 0 |
| Pollakiuria | 31 (30.7) | 1 (1.0) | 0 | 0 |
| Micturition urgency | 18 (17.8) | 0 | 0 | 0 |
| Fatigue | 13 (12.9) | 2 (2.0) | 7 (12.1) | 0 |
| Hematuria | 13 (12.9) | 2 (2.0) | 0 | 0 |
| Hypothyroidism | 11 (10.9) | 1 (1.0) | 4 (6.9) | 0 |
| Hyperthyroidism | 11 (10.9) | 0 | 3 (5.2) | 0 |
| Urinary tract infection | 11 (10.9) | 3 (3.0) | 0 | 0 |
| Lipase increased | 8 (7.9) | 1 (1.0) | 4 (6.9) | 1 (1.7) |
| Bladder spasm | 7 (6.9) | 0 | 0 | 0 |
| Decreased appetite | 7 (6.9) | 0 | 0 | 0 |
| Asthenia | 6 (5.9) | 0 | 0 | 0 |
| Hyperamylasemia | 6 (5.9) | 0 | 4 (6.9) | 1 (1.7) |
| Urinary incontinence | 6 (5.9) | 1 (1.0) | 0 | 0 |
| Bladder pain | 5 (5.0) | 1 (1.0) | 0 | 0 |
| Constipation | 5 (5.0) | 0 | 1 (1.7) | 0 |
| Diarrhea | 5 (5.0) | 0 | 3 (5.2) | 0 |
| Pruritus | 5 (5.0) | 0 | 7 (12.1) | 0 |
| Urethral pain | 5 (5.0) | 0 | 0 | 0 |
| Hyponatremia | 3 (3.0) | 1 (1.0) | 3 (5.2) | 2 (3.4) |
| Arthralgia | 2 (2.0) | 0 | 4 (6.9) | 0 |
| AST increased | 2 (2.0) | 1 (1.0) | 4 (6.9) | 1 (1.7) |
| ALT increased | 2 (2.0) | 1 (1.0) | 3 (5.2) | 1 (1.7) |
| Immune-related TRAE | 48 (47.5) | 8 (7.9) | 29 (50.0) | 5 (8.6) |
| Patients With ≥1 Event | Any Grade | Any Grade | ||
| Serious TRAEc | 14 (13.9) | 3 (5.2) | ||
| TRAE leading to death | 0 | 1 (1.7)d | ||
| TRAE leading to treatment discontinuatione | 21 (20.8) | 0 | ||
| TRAE leading to discontinuation of TAR-200f | 18 (17.8) | — | ||
| TRAE leading to discontinuation of cetrelimabg | 11 (10.9) | 0 | ||
Abbreviations: AE, adverse event; MIBC, muscle-invasive bladder cancer; TRAE, treatment-related adverse event.
AE is categorized as related if assessed by investigator as possibly, probably, or very likely related to study treatment. Patients were counted only once for any given AE, regardless of the number of times the AE occurred.
TRAEs by preferred term are listed if events of any grade were reported in ≥5% of patients in either cohort. Other grade ≥3 TRAEs included acute kidney injury (cohort 2, n = 2 [3.4%]) and blood creatine phosphokinase increased (cohort 1, n = 1 [1.0%]; cohort 2, n = 1 [1.7%]); all other grade ≥3 TRAEs occurred in one patient each (full list in the Data Supplement).
The most frequent serious TRAEs (reported in ≥2 patients) were hyponatremia (cohort 1, n = 1 [1.0%]; cohort 2, n = 2 [3.4%]), tubulointerstitial nephritis (cohort 1, n = 2 [2.0%]; cohort 2, n = 0), and urinary tract infection (cohort 1, n = 2 [2.0%]; cohort 2, n = 0).
Case of hyperglycemic hyperosmolar nonketotic syndrome.
TRAE leading to discontinuation of TAR-200, cetrelimab, or both.
The most frequent TRAEs leading to TAR-200 discontinuation were pollakiuria (n = 4 [4.0%]), noninfective cystitis (n = 3 [3.0%]), and bladder pain (n = 2 [2.0%]). All other TRAEs leading to TAR-200 discontinuation occurred in one patient each (full list in the Data Supplement).
All TRAEs (by preferred term) leading to cetrelimab discontinuation occurred in one patient each (full list in the Data Supplement).
Sixteen patients (15.8%) had grade ≥3 TRAEs with TAR-200 plus cetrelimab, most frequently urinary tract infection (3.0%), fatigue (2.0%), and hematuria (2.0%). Six patients had grade ≥3 TRAEs with cetrelimab monotherapy, most frequently hyponatremia (3.4%) and acute kidney injury (3.4%). Fourteen patients (13.9%) treated with TAR-200 plus cetrelimab had serious TRAEs, with tubulointerstitial nephritis (2.0%) and urinary tract infection (2.0%) most frequent. Three patients (5.2%) treated with cetrelimab monotherapy had serious TRAEs, with hyponatremia (3.4%) most frequent. Immune-related TRAEs occurred at similar rates in patients who received TAR-200 plus cetrelimab (47.5%) or cetrelimab monotherapy (50.0%).
No TRAEs leading to death were reported with TAR-200 plus cetrelimab. One TRAE leading to death was reported in a patient treated with cetrelimab monotherapy (hyperglycemic hyperosmolar nonketotic syndrome).
Twenty-one patients (20.8%) treated with TAR-200 plus cetrelimab discontinued one or both study treatments because of TRAEs. The most frequent TRAEs leading to TAR-200 discontinuation were pollakiuria (4.0%) and noninfective cystitis (3.0%). No patients discontinued cetrelimab monotherapy because of TRAEs.
Biomarker Analysis
Across both cohorts, 55 of 67 patients (82.1%) with available utDNA MRD results (Data Supplement, Fig S4) were utDNA positive at baseline (Fig 3A), and utDNA status was correlated with genomic disease burden (Data Supplement, Fig S5). These findings were consistent in patients with visibly complete (81.8%) or visibly incomplete TURBT (83.3%; Data Supplement, Fig S6). At week 12 (after neoadjuvant treatment), utDNA positivity was reduced across cohorts; 34 of 65 patients (52.3%) were utDNA positive. The trend was consistent in each cohort separately (Data Supplement, Fig S7) and generally consistent in T2 disease or T3-T4a disease subgroups, although data were limited (Data Supplement, Fig S8).
FIG 3.
Analysis of MRD biomarker detected by utDNA and ctDNA in patients with MIBC treated with neoadjuvant TAR-200 plus cetrelimab or cetrelimab monotherapy (both cohorts combined). (A) Prevalence of utDNA MRD-positive status at baseline and week 12 and prevalence of utDNA MRD clearance at week 12 across both cohorts. (B) Baseline and week 12 utDNA MRD status and pathologic response across both cohorts (left). Each column represents one patient. ROC curve for week 12 utDNA MRD status versus pCR (right); 95% confidence interval for area under the ROC curve is shown. (C) Baseline and week 12 ctDNA MRD status and pathologic response across both cohorts. Each column represents one patient. (D) Association between RFS and baseline ctDNA MRD status (left) and week 12 ctDNA MRD status (right). ctDNA, circulating tumor DNA; MIBC, muscle-invasive bladder cancer; MRD, molecular residual disease; pCR, pathologic complete response; pOR, pathologic overall response; pPR, pathologic partial response; RFS, recurrence-free survival; ROC, receiver operating characteristic; utDNA, urinary tumor DNA.
Week 12 utDNA status before RC was strongly associated with pathologic response (Fig 3B; Data Supplement, Table S5). Twenty-two of 27 patients (81.5%) who achieved pCR were utDNA negative at week 12 compared with 7 of 33 (21.2%) who did not achieve pCR (Fisher test, P = 5.4 × 10–6). The receiver operating characteristic for utDNA status predicting pCR was 0.80 (95% CI, 0.70 to 0.90), with a negative predictive value of 0.81. Similar results were seen in each cohort (Data Supplement, Fig S9). utDNA clearance, defined as utDNA-positive status at baseline and utDNA-negative at week 12, was strongly associated with pCR (Data Supplement, Fig S10). Fourteen of 30 patients (46.7%) with available data had utDNA clearance (7/18 in cohort 1; 7/12 in cohort 2). Twelve of 15 patients (80.0%) who were utDNA positive at baseline and achieved pCR had utDNA clearance, compared with 2 of 15 (13.3%) who did not achieve pCR (Fisher test, P = .0006). The results were similar in each cohort.
Across both cohorts, MRD detected by plasma ctDNA (Data Supplement, Fig S11) was reduced after 12 weeks of neoadjuvant treatment, although pCR was not significantly associated with week 12 ctDNA status (P = .12; Fig 3C and Data Supplement, Fig S12). Eleven of 20 patients (55.0%) with available data had ctDNA clearance (7/12 in cohort 1; 4/8 in cohort 2; Data Supplement, Fig S13). ctDNA clearance was not significantly associated with pCR (Fisher test, P = .15).
Baseline and week 12 ctDNA-negative status were associated with longer RFS (Fig 3D). The hazard ratios for RFS in patients with baseline and week 12 ctDNA-positive status versus ctDNA-negative status were 4.42 (95% CI, 0.91 to 21.3; log-rank, P = .04) and 4.66 (95% CI, 1.24 to 17.4; log-rank, P = .01), respectively. Differences in RFS by ctDNA status were not statistically significant in either cohort separately (Data Supplement, Fig S14).
DISCUSSION
In the primary analysis of the parallel-cohort, randomized phase II SunRISe-4 study, neoadjuvant TAR-200 plus cetrelimab (cohort 1) showed a pCR rate of 37.5%, whereas cetrelimab monotherapy (cohort 2) showed a pCR rate of 28.3%. Hence, the addition of the TAR-200 to cetrelimab provided a clinically meaningful gain in the pCR rate (difference, +9.2%). The lower bound of the 95% CI exceeded the prespecified 20% threshold for TAR-200 plus cetrelimab but did not for cetrelimab monotherapy. Higher pCR rates in patients treated with TAR-200 plus cetrelimab compared with cetrelimab monotherapy were consistent across subgroups and sensitivity analyses. The pOR rate, corresponding to pathologic downstaging to ≤pT1N0, was also higher with TAR-200 plus cetrelimab than cetrelimab monotherapy (53.4% v 43.5%), further supporting the contribution of TAR-200 to cetrelimab.
Acknowledging differences in patient populations and limitations to cross-trial comparisons, the pCR rate in the cetrelimab monotherapy cohort (28.3%) was comparable with pCR rates observed with single-agent PD-(L)1 checkpoint inhibitors in the neoadjuvant MIBC setting (31%-37%)24-26 and compares favorably with RC alone (12%-15%).6,15,16
The extent to which pCR serves as a surrogate for survival outcomes in patients with MIBC has been subject to debate, although existing literature suggests that pCR is correlated with a reduction in the risk of death and recurrence.15,30 Thus, RFS is a key secondary end point at the primary analysis of SunRISe-4. Acknowledging the relatively short follow-up at present (median, 14.1 months), 12-month RFS rates of 77.4% in patients who received TAR-200 plus cetrelimab and 64.1% in those who received cetrelimab monotherapy in SunRISe-4 provide early evidence that TAR-200 plus cetrelimab may confer an RFS benefit.
Notably, more than half of the SunRISe-4 population were patients who refused cisplatin; thus, the findings are relevant beyond the cisplatin-ineligible MIBC population. The pCR rate with TAR-200 plus cetrelimab (37.5%) compares favorably with that reported in the recent NIAGARA study (in which pCR was a coprimary end point), where cisplatin-eligible patients were randomly assigned to receive neoadjuvant GC plus durvalumab (37%) or neoadjuvant GC alone (26%).5 In SunRISe-4, a high pCR rate was achieved with local chemotherapy delivered via TAR-200 and a systemic checkpoint inhibitor, whereas both neoadjuvant chemotherapy and checkpoint inhibition were administered systemically in NIAGARA.5
Standard of care for MIBC is evolving in two key areas. First, trials have shown a survival benefit with adjuvant treatment with immune checkpoint inhibitors following RC in patients with high-risk features.5,31,32 Second, ongoing trials seek to identify new therapeutic combinations in the neoadjuvant setting, either in combination with cisplatin or without.33 Critical to the impact of these trials will be safety and tolerability among this older, medically complex population, in addition to pCR and longer-term oncologic outcomes such as RFS and overall survival. As pCR rates continue to improve, the treatment landscape will continue to evolve toward potential bladder-sparing approaches. Such strategies must be coupled with careful surveillance in the setting of this lethal disease.
Overall, TRAEs in patients who received TAR-200 plus cetrelimab were manageable with a safety profile consistent with each component separately in patients with MIBC20,21 and in other patient populations.18,23,34 TRAEs did not affect the timing of RC, with few surgeries delayed (8.2% after week 15).
Exploratory biomarker analysis in SunRISe-4 showed that 12 weeks of neoadjuvant treatment in either cohort reduced MRD as measured by utDNA or ctDNA. utDNA-positive status was detected in most patients (approximately 80%) irrespective of TURBT completeness, underscoring the presence of active disease despite visually complete resection. Both presurgery utDNA status and utDNA clearance were strongly correlated with pCR, supporting continued investigation of utDNA as a marker of local disease control in MIBC.35,36 Given the evolving landscape, discovery of a highly sensitive marker of intravesical disease will be critically important. To our knowledge, SunRISe-4 is the largest study to date to explore utDNA as a potential biomarker in the setting of MIBC. Unlike utDNA, MRD as measured by ctDNA was not strongly associated with pathologic response. However, ctDNA status at baseline or presurgery was correlated with longer RFS, supporting further investigation of ctDNA as a marker of systemic control in MIBC.37
To our knowledge, SunRISe-4 is the first study to demonstrate the contribution to pathologic response at RC from neoadjuvant treatment with TAR-200, delivering sustained local chemotherapy within the bladder, in combination with a checkpoint inhibitor. pCR was robustly evaluated in this study, assessed by both central, blinded pathologic review as well as pathologic review at the site at which RC was performed, with high concordance between both.
Limitations of the study include the open-label, noncomparative design, the limited survival follow-up at the primary analysis, and the exclusion of patients with residual tumors >3 cm. Although the primary efficacy results support further studies on bladder-sparing treatment approaches, SunRISe-4 was not designed to evaluate bladder-sparing treatment. As the biomarker analyses were exploratory, these data are not intended to inform treatment decisions, but they may support future biomarker studies in MIBC.
Collectively, the primary analysis results of SunRISe-4 demonstrate a favorable benefit-risk profile of neoadjuvant TAR-200 plus cetrelimab in patients with MIBC who are ineligible for or refuse NAC before RC. These findings emphasize the potential role of TAR-200 in enhancing systemic checkpoint inhibition in the neoadjuvant MIBC setting, applicable to both cisplatin-ineligible patients and those who are cisplatin-eligible but refuse treatment.
ACKNOWLEDGMENT
The authors would like to thank the patients who participated in the study, their families, and the investigators and clinical research staff from the study centers. Writing assistance was provided by Benjamin Ricca, PhD, of Johnson & Johnson.
Andrea Necchi
This author is an Associate Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript.
Employment: Bayer (I)
Stock and Other Ownership Interests: Bayer (I)
Consulting or Advisory Role: Merck Sharp & Dohme, AstraZeneca, Incyte, Seattle Genetics/Astellas, Bristol Myers Squibb, Catalym, Gilead Sciences, Genenta Science, Johnson & Johnson/Janssen, PeerView, PeerVoice, Merck Serono, Samsung Bioepis, Bicycle Therapeutics
Research Funding: Merck Sharp & Dohme (Inst), Gilead Sciences (Inst), Bristol Myers Squibb/Celgene (Inst)
Travel, Accommodations, Expenses: Merck Sharp & Dohme, AstraZeneca, Johnson & Johnson/Janssen, Gilead Sciences
Félix Guerrero-Ramos
Stock and Other Ownership Interests: Pfizer, CG Oncology, Johnson & Johnson/Janssen
Honoraria: AstraZeneca, Johnson & Johnson/Janssen, BMS GmbH & Co. KG, Combat Medical, Merck, Pfizer, Nucleix, Roche, Palex, Johnson & Johnson/Janssen, MSD Oncology
Consulting or Advisory Role: AstraZeneca, Pfizer, Janssen Oncology, BMS GmbH & Co. KG, Johnson & Johnson/Janssen, Roche, Nucleix, Merck, Menarini Group, Photocure
Speakers' Bureau: Pfizer, Janssen Oncology, AstraZeneca, Combat Medical, Nucleix, BMS GmbH & Co. KG, Palex
Research Funding: Roche, Combat Medical
Patents, Royalties, Other Intellectual Property: BlaDimiR, miRNA-based diagnostic urine test
Expert Testimony: Nucleix, Johnson & Johnson/Janssen, Menarini Group
Travel, Accommodations, Expenses: Johnson & Johnson/Janssen, AstraZeneca, Janssen Oncology, Ipsen, Combat Medical, Nucleix, Recordati, Pfizer, SALVAT, Italfarmaco, Fidia Farmaceutici S. p. A
Bernardo Herrera-Imbroda
Consulting or Advisory Role: Astellas Pharma, Johnson & Johnson/Janssen, Bayer, AstraZeneca, Bristol Myers Squibb/Medarex, Recordati
Speakers' Bureau: Johnson & Johnson/Janssen, Astellas Pharma
Research Funding: Johnson & Johnson/Janssen (Inst)
Rohan Garje
Honoraria: Novartis
Research Funding: Exelixis (Inst), Janssen Oncology (Inst)
Bernadett Szabados
Honoraria: Johnson & Johnson, Merck Serono, MSD, Pfizer, Astellas Pharma, Photocure
Research Funding: Roche/Genentech (Inst)
Travel, Accommodations, Expenses: Johnson & Johnson/Janssen
Charles C. Peyton
Consulting or Advisory Role: UroGen Pharma, Janssen Biotech
Expert Testimony: Bradley Law firm
Benjamin Pradere
Honoraria: Johnson & Johnson/Janssen, Ipsen, Astellas Pharma, Pierre Fabre
Consulting or Advisory Role: Johnson & Johnson/Janssen, Pfizer, AstraZeneca, MSD Oncology
Travel, Accommodations, Expenses: Ipsen, Pierre Fabre
Neal Shore
Stock and Other Ownership Interests: Photocure
Consulting or Advisory Role: Bayer, Johnson & Johnson/Janssen, Dendreon, Tolmar, Ferring, Medivation/Astellas, Amgen, Pfizer, AstraZeneca, Astellas Pharma, Merck, Bristol Myers Squibb/Sanofi, Exact Imaging, InVitae, MDxHealth, Myriad Genetics, Sanofi, UroGen Pharma, Speciality Networks, Clarity Pharmaceuticals, Lantheus Medical Imaging, Lilly, Photocure, Telix Pharmaceuticals, Asieris Pharmaceuticals, Minomic, Novartis, PlatformQ Health, Promaxo, Protara Therapeutics, Fize Medical, Accord Research, Antev, Aura Biosciences, Bioprotect, Sumitomo Pharma Oncology, Siemens, Alessa Therapeutics, CG Oncology, Glytherix, Tutelix, ImmunityBio, Nusano
Research Funding: AbbVie, Amgen, Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, Boston Scientific, Clovis Oncology, Dendreon, Exact Imaging, Ferring, Foundation Medicine, InVitae, Johnson & Johnson/Janssen, MDxHealth, Merck, Myovant Sciences, Myriad Genetics, Nymox, Pfizer, Sanofi, Sesen Bio, Tolmar, CG Oncology, DisperSol, FORMA Therapeutics, Guardant Health, Jiangsu Yahong Meditech, Novartis, Pacific Edge, POINT Biopharma, Propella Therapeutics, SeaGen, MT Group, Theralase, Veru, Zenflow, Advantagene, Aragon Pharmaceuticals, Endocyte, Exelixis, FKD Therapies, Genentech, Istari Oncology, Medivation, OncoCellMDx, ORIC Pharmaceuticals, Palette Life Sciences, Plexxikon, RhoVac, Steba Biotech, UroGen Pharma, Urotronic, US Biotest, Vaxiion
Martin Bögemann
Employment: Johnson & Johnson/Janssen
Honoraria: Janssen-Cilag, Astellas Pharma, Bayer/Vital, Sanofi/Aventis, MSD, Bristol Myers Squibb, Pfizer, Novartis, Ipsen, EUSA Pharma, Merck, Eisai, Amgen, AstraZeneca, Roche, Advanced Accelerator Applications
Consulting or Advisory Role: Bayer, Janssen-Cilag, Astellas Pharma, AstraZeneca, MSD, Bristol Myers Squibb, Ipsen, Roche, Novartis, Merck, Sanofi, Eisai, Gilead Sciences
Research Funding: Janssen-Cilag, IPSEN (Inst)
Travel, Accommodations, Expenses: Janssen-Cilag, Bayer, Amgen, BMS GmbH & Co. KG
Mark A. Preston
Consulting or Advisory Role: Bayer, Johnson & Johnson/Janssen, Pfizer
Research Funding: Merck
Patents, Royalties, Other Intellectual Property: Chapter author on prostate cancer screening for UpToDate
Travel, Accommodations, Expenses: Koelis, da Vinci Surgery
Evanguelos Xylinas
Employment: W.L. Gore & Associates (I)
Consulting or Advisory Role: Pfizer, Ferring, Boston Scientific
Research Funding: Ferring
Cristina Sanchez de Llano
Employment: Johnson & Johnson/Janssen
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Travel, Accommodations, Expenses: Johnson & Johnson/Janssen
Cinty Gong
Employment: Johnson & Johnson/Janssen
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Mohamad Hasan
Employment: Johnson & Johnson/Janssen
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Karen Urtishak
Employment: Johnson & Johnson/Janssen
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Patents, Royalties, Other Intellectual Property: Patents
Sebastiano Battaglia
Employment: Johnson and Johnson
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Hind Stitou
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Travel, Accommodations, Expenses: Johnson & Johnson
Sumeet Bhanvadia
Employment: Advantage Healthcare Services (I), Johnson & Johnson/Janssen
Research Funding: Johnson & Johnson/Janssen
Travel, Accommodations, Expenses: Intuitive Surgical, Photocure
Hussein Sweiti
Employment: Johnson & Johnson/Janssen
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Patents, Royalties, Other Intellectual Property: FGFR Tyrosine Kinase Inhibitors for the Treatment of Advanced Solid Tumors
Sarah P. Psutka
Honoraria: AstraZeneca
Consulting or Advisory Role: Merck, Johnson & Johnson/Janssen, ImmunityBio, CG Oncology, Ferring
Research Funding: Steba Biotech, Johnson & Johnson/Janssen
Travel, Accommodations, Expenses: Medtronic
No other potential conflicts of interest were reported.
PRIOR PRESENTATION
Presented in part at the European Society for Medical Oncology Congress, Berlin, Germany, October 17-21, 2025.
SUPPORT
Supported by Johnson & Johnson company.
CLINICAL TRIAL INFORMATION
A.N. and F.G.-R. contributed equally to this work.
Supplementary Materials
Protocols
DATA SHARING STATEMENT
A data sharing statement provided by the authors is available with this article at DOI https://doi.org/10.1200/JCO-25-02382.
Janssen Pharmaceutical Companies of Johnson & Johnson's data sharing policy is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for study data access can be submitted through the Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.
AUTHOR CONTRIBUTIONS
Conception and design: Andrea Necchi, Félix Guerrero-Ramos, Cristina Sanchez de Llano, Cinty Gong, Mohamad Hasan, Karen Urtishak, Sebastiano Battaglia, Hind Stitou, Sumeet Bhanvadia, Hussein Sweiti, Sarah P. Psutka
Provision of study materials or patients: Neal Shore, Mark A. Preston, Evanguelos Xylinas, Sarah P. Psutka
Collection and assembly of data: All authors
Data analysis and interpretation: All authors
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Gemcitabine Intravesical System Plus Cetrelimab or Cetrelimab Alone as Neoadjuvant Therapy in Muscle-Invasive Bladder Cancer: SunRISe-4 Primary Analysis and Biomarker Results
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
Andrea Necchi
This author is an Associate Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript.
Employment: Bayer (I)
Stock and Other Ownership Interests: Bayer (I)
Consulting or Advisory Role: Merck Sharp & Dohme, AstraZeneca, Incyte, Seattle Genetics/Astellas, Bristol Myers Squibb, Catalym, Gilead Sciences, Genenta Science, Johnson & Johnson/Janssen, PeerView, PeerVoice, Merck Serono, Samsung Bioepis, Bicycle Therapeutics
Research Funding: Merck Sharp & Dohme (Inst), Gilead Sciences (Inst), Bristol Myers Squibb/Celgene (Inst)
Travel, Accommodations, Expenses: Merck Sharp & Dohme, AstraZeneca, Johnson & Johnson/Janssen, Gilead Sciences
Félix Guerrero-Ramos
Stock and Other Ownership Interests: Pfizer, CG Oncology, Johnson & Johnson/Janssen
Honoraria: AstraZeneca, Johnson & Johnson/Janssen, BMS GmbH & Co. KG, Combat Medical, Merck, Pfizer, Nucleix, Roche, Palex, Johnson & Johnson/Janssen, MSD Oncology
Consulting or Advisory Role: AstraZeneca, Pfizer, Janssen Oncology, BMS GmbH & Co. KG, Johnson & Johnson/Janssen, Roche, Nucleix, Merck, Menarini Group, Photocure
Speakers' Bureau: Pfizer, Janssen Oncology, AstraZeneca, Combat Medical, Nucleix, BMS GmbH & Co. KG, Palex
Research Funding: Roche, Combat Medical
Patents, Royalties, Other Intellectual Property: BlaDimiR, miRNA-based diagnostic urine test
Expert Testimony: Nucleix, Johnson & Johnson/Janssen, Menarini Group
Travel, Accommodations, Expenses: Johnson & Johnson/Janssen, AstraZeneca, Janssen Oncology, Ipsen, Combat Medical, Nucleix, Recordati, Pfizer, SALVAT, Italfarmaco, Fidia Farmaceutici S. p. A
Bernardo Herrera-Imbroda
Consulting or Advisory Role: Astellas Pharma, Johnson & Johnson/Janssen, Bayer, AstraZeneca, Bristol Myers Squibb/Medarex, Recordati
Speakers' Bureau: Johnson & Johnson/Janssen, Astellas Pharma
Research Funding: Johnson & Johnson/Janssen (Inst)
Rohan Garje
Honoraria: Novartis
Research Funding: Exelixis (Inst), Janssen Oncology (Inst)
Bernadett Szabados
Honoraria: Johnson & Johnson, Merck Serono, MSD, Pfizer, Astellas Pharma, Photocure
Research Funding: Roche/Genentech (Inst)
Travel, Accommodations, Expenses: Johnson & Johnson/Janssen
Charles C. Peyton
Consulting or Advisory Role: UroGen Pharma, Janssen Biotech
Expert Testimony: Bradley Law firm
Benjamin Pradere
Honoraria: Johnson & Johnson/Janssen, Ipsen, Astellas Pharma, Pierre Fabre
Consulting or Advisory Role: Johnson & Johnson/Janssen, Pfizer, AstraZeneca, MSD Oncology
Travel, Accommodations, Expenses: Ipsen, Pierre Fabre
Neal Shore
Stock and Other Ownership Interests: Photocure
Consulting or Advisory Role: Bayer, Johnson & Johnson/Janssen, Dendreon, Tolmar, Ferring, Medivation/Astellas, Amgen, Pfizer, AstraZeneca, Astellas Pharma, Merck, Bristol Myers Squibb/Sanofi, Exact Imaging, InVitae, MDxHealth, Myriad Genetics, Sanofi, UroGen Pharma, Speciality Networks, Clarity Pharmaceuticals, Lantheus Medical Imaging, Lilly, Photocure, Telix Pharmaceuticals, Asieris Pharmaceuticals, Minomic, Novartis, PlatformQ Health, Promaxo, Protara Therapeutics, Fize Medical, Accord Research, Antev, Aura Biosciences, Bioprotect, Sumitomo Pharma Oncology, Siemens, Alessa Therapeutics, CG Oncology, Glytherix, Tutelix, ImmunityBio, Nusano
Research Funding: AbbVie, Amgen, Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, Boston Scientific, Clovis Oncology, Dendreon, Exact Imaging, Ferring, Foundation Medicine, InVitae, Johnson & Johnson/Janssen, MDxHealth, Merck, Myovant Sciences, Myriad Genetics, Nymox, Pfizer, Sanofi, Sesen Bio, Tolmar, CG Oncology, DisperSol, FORMA Therapeutics, Guardant Health, Jiangsu Yahong Meditech, Novartis, Pacific Edge, POINT Biopharma, Propella Therapeutics, SeaGen, MT Group, Theralase, Veru, Zenflow, Advantagene, Aragon Pharmaceuticals, Endocyte, Exelixis, FKD Therapies, Genentech, Istari Oncology, Medivation, OncoCellMDx, ORIC Pharmaceuticals, Palette Life Sciences, Plexxikon, RhoVac, Steba Biotech, UroGen Pharma, Urotronic, US Biotest, Vaxiion
Martin Bögemann
Employment: Johnson & Johnson/Janssen
Honoraria: Janssen-Cilag, Astellas Pharma, Bayer/Vital, Sanofi/Aventis, MSD, Bristol Myers Squibb, Pfizer, Novartis, Ipsen, EUSA Pharma, Merck, Eisai, Amgen, AstraZeneca, Roche, Advanced Accelerator Applications
Consulting or Advisory Role: Bayer, Janssen-Cilag, Astellas Pharma, AstraZeneca, MSD, Bristol Myers Squibb, Ipsen, Roche, Novartis, Merck, Sanofi, Eisai, Gilead Sciences
Research Funding: Janssen-Cilag, IPSEN (Inst)
Travel, Accommodations, Expenses: Janssen-Cilag, Bayer, Amgen, BMS GmbH & Co. KG
Mark A. Preston
Consulting or Advisory Role: Bayer, Johnson & Johnson/Janssen, Pfizer
Research Funding: Merck
Patents, Royalties, Other Intellectual Property: Chapter author on prostate cancer screening for UpToDate
Travel, Accommodations, Expenses: Koelis, da Vinci Surgery
Evanguelos Xylinas
Employment: W.L. Gore & Associates (I)
Consulting or Advisory Role: Pfizer, Ferring, Boston Scientific
Research Funding: Ferring
Cristina Sanchez de Llano
Employment: Johnson & Johnson/Janssen
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Travel, Accommodations, Expenses: Johnson & Johnson/Janssen
Cinty Gong
Employment: Johnson & Johnson/Janssen
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Mohamad Hasan
Employment: Johnson & Johnson/Janssen
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Karen Urtishak
Employment: Johnson & Johnson/Janssen
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Patents, Royalties, Other Intellectual Property: Patents
Sebastiano Battaglia
Employment: Johnson and Johnson
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Hind Stitou
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Travel, Accommodations, Expenses: Johnson & Johnson
Sumeet Bhanvadia
Employment: Advantage Healthcare Services (I), Johnson & Johnson/Janssen
Research Funding: Johnson & Johnson/Janssen
Travel, Accommodations, Expenses: Intuitive Surgical, Photocure
Hussein Sweiti
Employment: Johnson & Johnson/Janssen
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Patents, Royalties, Other Intellectual Property: FGFR Tyrosine Kinase Inhibitors for the Treatment of Advanced Solid Tumors
Sarah P. Psutka
Honoraria: AstraZeneca
Consulting or Advisory Role: Merck, Johnson & Johnson/Janssen, ImmunityBio, CG Oncology, Ferring
Research Funding: Steba Biotech, Johnson & Johnson/Janssen
Travel, Accommodations, Expenses: Medtronic
No other potential conflicts of interest were reported.
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