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(gemcitabine intravesical system)

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INLEXZO™ (gemcitabine intravesical system)

Medical Information

INLEXZO - SunRISe-4 Study

Last Updated: 10/22/2025

SUMMARY

  • SunRISe-4 (NCT04919512) is an ongoing, phase 2, randomized, open-label, multicenter study evaluating the efficacy and safety of INLEXZO in combination with systemic cetrelimab, an investigational immunoglobulin G4 (IgG4) antibody that targets the programmed cell death protein-1 (PD-1) receptor, and systemic cetrelimab alone as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) who are scheduled for radical cystectomy (RC) and refuse or are ineligible for platinum-based neoadjuvant chemotherapy. The primary endpoint is pathologic complete response (pCR).1-5
  • Necchi et al (2025)2 reported the primary efficacy and safety results for patients with MIBC who were randomized to receive INLEXZO + cetrelimab therapy (cohort 1, n=101) vs cetrelimab monotherapy (cohort 2, n=58). Exploratory biomarker analyses of urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) minimal residual disease (MRD) are reported in association with efficacy measures.
    • Of the population treated with the combination of INLEXZO + cetrelimab (n=88), the pCR and pathologic overall response (pOR) rates were 38% (95% confidence interval [CI], 28-49) and 44% (95% CI, 43-64), respectively. One-year recurrence-free survival rate was 77% (n=35 at risk; 95% CI, 67-85).
    • Of the population treated with cetrelimab monotherapy (n=46), the pCR and pOR rates were 23% (95% CI, 10-41) and 35% (95% CI, 19-55), respectively. One-year recurrence-free survival rate was 64% (n=20 at risk; 95% CI, 47-77).
    • One or more treatment-related adverse events (TRAEs; any grade) were reported in 81.2% (82/101) and 51.7% (30/58) of patients who received INLEXZO + cetrelimab and cetrelimab monotherapy, respectively.
    • Observed TRAEs (any grade) in patients who received INLEXZO + cetrelimab included dysuria (30.7%), pollakiuria (30.7%), micturition urgency (17.8%), fatigue (12.9%), hematuria (12.9%), hypothyroidism (10.9%), hyperthyroidism (10.9%), urinary tract infection (10.9%), and pruritius (5.0%).
    • The rate of discontinuation due to TRAEs was 20.8% (21/101) with INLEXZO + cetrelimab.
  • Necchi et al (2025)4 reported the interim efficacy and safety results for patients with MIBC who were randomized to receive either INLEXZO + cetrelimab therapy (cohort 1, n=79) or cetrelimab monotherapy (cohort 2, n=41).
    • Of the efficacy-evaluable population treated with the combination of INLEXZO + cetrelimab (n=53), the pCR and pOR rates were 42% (95% CI, 28-56) and 60% (95% CI, 46-74), respectively.
    • Of the efficacy-evaluable population treated with cetrelimab monotherapy (n=31), pCR and pOR rates were 23% (95% CI, 10-41) and 35% (95% CI, 19-55), respectively.
    • One or more TRAEs (any grade) were reported in 72.2% (57/79) and 43.9% (18/41) of patients who underwent INLEXZO + cetrelimab and cetrelimab monotherapy, respectively.
    • The most frequent TRAEs with INLEXZO + cetrelimab were grade 1-2 urinary events.
    • The rate of discontinuation due to TRAEs was 12.7% (10/79) with INLEXZO + cetrelimab.
  • Psutka et al (2025)6 presented preliminary perioperative outcomes (surgical, laboratory, and safety) for patients with MIBC who received INLEXZO + cetrelimab therapy (cohort 1, n=79) or cetrelimab monotherapy (cohort 2, n=41).
    • In the RC-evaluable set (n=76; cohort 1, n=50; cohort 2, n=26):
      • Median time from neoadjuvant treatment initiation to RC was 13.5 weeks (range, 4.1-19.4); 84% (64/76) of patients underwent RC within the protocol-specified window (11-15 weeks).
      • The 30- and 90-day post-RC morbidity and mortality profiles in both cohorts were consistent with historical data.

Product labeling

BACKGROUND

  • INLEXZO (gemcitabine intravesical system) is an intravesical drug releasing system (iDRS), referred to as TAR-200 in literature. INLEXZO is designed to provide local release of gemcitabine in the bladder. INLEXZO contains gemcitabine and urea minitablets within a dual-lumen silicone tube for gradual release of gemcitabine by an osmotic delivery mechanism through the prescribed indwelling period.4,5,7-12
  • INLEXZO is inserted intravesically via urinary placement catheter, after which it self-coils into a bi-oval shape (see Figure: INLEXZO iDRS). Removal of INLEXZO can be achieved using grasping forceps and cystoscopy.10,13

INLEXZO iDRS7,8,11,14

A graphic design of a train track AI-generated content may be incorrect.

CLINICAL DATA

SunRISe-4 Study

Necchi et al (2025)2 reported the primary efficacy and safety results of INLEXZO + cetrelimab therapy vs cetrelimab monotherapy in patients with MIBC who were ineligible for or decline neoadjuvant cisplatin-based chemotherapy. Exploratory biomarker analyses of utDNA and ctDNA MRD were also included.

Study Design/Methods

  • Ongoing, phase 2, randomized, open-label, multicenter study1,2,4,5
  • The study design is shown in Figure: SunRISe-4 Study Design.
  • RC could be performed at week 12. The protocol-specific window for RC was 11-15 weeks.4,6
    • RC could not be performed before week 11 unless at the investigator’s discretion. It could not be performed later than 3 weeks from the week 12 visit.4 
  • utDNA MRD was assessed by UROAmp assay (Convergent Genomics, USA), and ctDNA MRD was assessed by Natera Signatera Assay (Natera, Inc., USA).2

SunRISe-4 Study Design1,2,4-6,13 

Abbreviations: CT, computed tomography; CTCAE, Common Terminology Criteria for Adverse Events; cTNM, clinical stage-primary tumor [T], lymph node [N], distant metastasis [M]; ECOG PS, Eastern Cooperative Oncology Group performance status; EOS, end of study; FACT-Bl, Functional Assessment of Cancer Therapy-Bladder; IV, intravenously; MIBC, muscle-invasive bladder cancer; MRI, magnetic resonance imaging; pCR, pathologic complete response; pOR, pathologic overall response; Q12W, every 12 weeks; Q3W, every 3 weeks; Q4W, every 4 weeks; R, randomization; RC, radical cystectomy; RECIST, Response Evaluation Criteria in Solid Tumors; RFS, recurrence-free survival; TURBT, transurethral resection of bladder tumor.
aPer RECIST v1.1 or histologic evidence.
bPatients with variant histologic subtypes (except small-cell or neuroendocrine variants) were allowed if tumors demonstrated urothelial predominance.
cINLEXZO was placed intravesically via a transurethral placement catheter and then removed cystoscopically. Upon removal, a new gemcitabine intravesical system could be placed immediately.
dProtocol specified window of weeks 11-15.
eClinical follow-up visits and laboratory tests, including urine culture at all visits. Cross-sectional imaging (CT/MRI of chest, abdomen, and pelvis) was performed at week 6 during treatment and week 12 after RC.
fThe pCR rate was defined as the proportion of patients with pCR (no residual disease = ypT0N0) on analysis of RC bladder specimen by central pathology review.
gRFS was defined as the time from the first dose of any study treatment to the first evidence of radiographic progression (per RECIST v1.1) precluding RC, radiographic evidence of nodal or metastatic disease after RC, death due to any cause, or the last study disease assessment.
hSafety assessed as frequency and grade of adverse events (CTCAE v.5) and laboratory abnormalities.

Results

Patient Characteristics

Primary Analysis: Patient Characteristics in the INLEXZO + Cetrelimab (Cohort 1) and Cetrelimab Monotherapy (Cohort 2) Groups2 
Characteristic
Cohort 1:
INLEXZO + Cetrelimab
(n=101)
Cohort 2:
Cetrelimab Monotherapy
(n=58)
Age, median (IQR), years
74 (69-77)
69 (64-74)
Sex, male, n (%)
86 (85.1)
46 (79.3)
Race, n (%)
   White
72 (71.3)
43 (74.1)
   Asian
18 (17.8)
11 (19.0)
   Other
11 (10.9)
4 (6.9)
Geographic region, n (%)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, n (%)
   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 PS, n (%)
   0
83 (82.2)
45 (77.6)
   1
18 (17.8)
13 (22.4)
Tumor stage at initial diagnosis, n (%)
   T2
79 (78.2)
49 (84.5)
   T3
19 (18.8)
8 (13.8)
   T4a
3 (3.0)
1 (1.7)
Prior intravesical therapy, n (%)
12 (11.9)
9 (15.5)
Residual disease (visibly incomplete TURBT), n (%)
19 (18.8)
8 (13.8)
PD-L1 status, n (%)b
   Low
33 (50.8)
23 (74.2)
   High
32 (49.2)
8 (25.8)
Urothelial carcinoma with variant histology, n (%)
22 (21.8)
16 (27.6)
Reason for not receiving neoadjuvant cisplatin-based chemotherapy, n (%)
   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 PS, Eastern Cooperative Oncology Group performance status; IQR, interquartile range; PD-L1, programmed death-ligand 1; TURBT, transurethral resection of bladder tumor. aAmerica includes the United States; Asia includes Israel and South Korea; Western Europe includes Belgium, France, Germany, Italy, Netherlands, Poland, Spain, and the United Kingdom.bPercentages are based on number of patients with available PD-L1 status data. Cohort 1 and cohort 2 included 65 and 31 patients with available data, respectively.
Efficacy

Primary Analysis: Efficacy Endpoints in the INLEXZO + Cetrelimab (Cohort 1) and INLEXZO Monotherapy (Cohort 2) Groups2
Endpoint, % (95% CI)
Cohort 1:
INLEXZO + Cetrelimab
Cohort 2:
Cetrelimab Monotherapy
n=88
n=46
pCR by central reviewa
38 (28-49)
28 (16-44)
pOR
53 (43-64)
44 (29-59)
n=35
n=20
12-month RFSb
77 (67-85)
64 (47-77)
Abbreviations: CI, confidence interval; pCR, pathologic complete response (defined as ypT0N0); pOR, pathologic overall response (defined as ≤ypT1N0); RC, radical cystectomy; RFS, recurrence-free rate.
aData are shown for the efficacy-evaluable set (n=134) defined as patients who underwent cystectomy and had available centrally review histopathology.
bRFS 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. Data are shown for each timepoint with ≥5 patients in either cohort.
  • Higher pCR was observed in cohort 1 across stratification factors.3
Safety

Primary Analysis: TRAEs in the INLEXZO + Cetrelimab (Cohort 1) and INLEXZO Monotherapy (Cohort 2) Groups2
Patients With ≥1 Event, n (%)
Cohort 1:
INLEXZO + Cetrelimab
(n=101)
Cohort 2:
Cetrelimab Monotherapy
(n=58)
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
   Pruritus
5 (5.0)
0
7 (12.1)
0
Immune-related TRAE
48 (47.5)
8 (7.9)
29 (50.0)
5 (8.6)
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 TAR-200 discontinuationf
18 (17.8)
-
-
-
   TRAE leading to cetrelimab discontinuationg
11 (10.9)
-
0
-
Abbreviations: AE, adverse event; TRAE, treatment-related adverse event. aAE was 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. bTRAEs by preferred term are listed if events of any grade were reported in ≥10% of patients in either cohort. Most frequent grade ≥3 TRAEs in cohort 1 were urinary tract infection (n=3 [3.0%]), fatigue (n=2 [2.0%]), and hematuria (n=2 [2.0%]). Most frequent grade ≥3 TRAEs in cohort 2 were hyponatremia (n=2 [3.4%]) and acute kidney injury (n=2 [3.4%]).cThe 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). dCase of hyperglycemic hyperosmolar nonketotic syndrome. eTRAE leading to discontinuation of TAR-200, cetrelimab, or both. fThe 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.
gAll TRAEs leading to cetrelimab discontinuation occurred in 1 patient each.
Exploratory Biomarker Analyses

Exploratory utDNA MRD Analysis in SunRISe-4 (Cohort 1 + Cohort 2)2,3
Cohort 1
Cohort 2
Cohort 1 + Cohort 2
MRD+, %
MRD+, %
MRD+, %
MRD-, %
Baseline
77.8 (n=45a)
90.9 (n=22a)
82.1 (n/N=55/67)
17.9 (n/N=12/67)
Week 12
50 (n=38a)
55.6 (n=27a)
52.3 (n/N=34/65)
47.7 (n/N=31/65)
Abbreviations: MRD, minimal residual disease; MRD-, minimal residual disease negativity; MRD+, minimal residual disease positivity; utDNA, urinary tumor DNA.
aPatients with available utDNA results.
  • Across both cohorts, there were 55 patients who had available utDNA and visibly complete TURBT and at baseline there were 81.8% who were utDNA+.
  • Across both cohorts, there were 12 patients who had available utDNA and visibly incomplete TURBT and at baseline there were 83.3% who were utDNA+.
  • Week 12 MRD- status and MRD clearance (defined as matching patients with baseline MRD+ and week 12 MRD- statuses) association with pathologic response are presented in Table: MRD Association With pCR.
    • Of the 30 patients who were utDNA+ at baseline and had matched week 12 utDNA results, 14 (46.7%) had utDNA clearance at week 12 (n=7 each in cohort 1 and cohort 2).

MRD Association With pCR2,3

pCR,
% (n/N)
Non-pCR,a
% (n/N)
P-Valueb
Week 12 MRD-
utDNA
81.5 (22/27)
21.2 (7/33)
<10-5
ctDNA
93 (13/14)
68 (19/28)
0.12
MRD clearance (baseline MRD+ and week 12 MRD-)
utDNAc
80.0 (12/15)
13.3 (2/15)
<10-3
ctDNA
83 (5/6)
43 (6/14)
0.15
Abbreviations: ctDNA, circulating tumor DNA; MRD, minimal residual disease; MRD-, minimal residual disease negativity; MRD+, minimal residual disease positivity; pCR, pathologic complete response; pOR, pathologic overall response (defined as ≤ypT1N0); pPR, pathologic partial response; utDNA, urinary tumor DNA.
aNon-pCR includes pPR and pOR.
bFisher’s test.
cutDNA clearance was shown in 7 patients each in cohorts 1 and 2.

ctDNA MRD Association With RFS2,3
Median RFS,
Months (95% CI)
Hazard Ratio (95% CI)
P-Valuea
Baseline ctDNA (n=44)
MRD-
NR
4.42 (0.91-21.3)
0.04
MRD+
17.8 (14.5-NR)
Week 12 ctDNA (n=44)
MRD-
NR
4.66 (1.24-17.4)
0.01
MRD+
14.5 (6.4-NR)
Abbreviations: CI, confidence interval; ctDNA, circulating tumor DNA; MRD, minimal residual disease; MRD-, minimal residual disease negativity; MRD+, minimal residual disease positivity; NR, not reached; RFS, recurrence-free survival.
aLog-rank test.

Necchi et al (2025)4 summarized the interim efficacy and safety results of INLEXZO + cetrelimab therapy vs cetrelimab monotherapy in patients with MIBC who were ineligible for or decline neoadjuvant cisplatin-based chemotherapy.

Results

Patient Characteristics

Patient Characteristics in the INLEXZO + Cetrelimab (Cohort 1) and Cetrelimab Monotherapy (Cohort 2) Groups4 
Characteristic
INLEXZO + Cetrelimab
Cohort 1
(n=79)
Cetrelimab Monotherapy
Cohort 2
(n=41)
Age, median (SD), years
73 (6.7)
67 (8.5)
Sex, male, n (%)
68 (86)
34 (83)
Race, n (%)
    White
52 (66)
29 (71)
    Asian
18 (23)
10 (24)
    Other
9 (11)
2 (5)
Region, n (%)
   USA
29 (37)
12 (29)
   Asia
19 (24)
11 (27)
   Western Europe
31 (39)
18 (44)
Nicotine use history, n (%)
   Current
20 (25)
11 (27)
   Former
39 (49)
22 (54)
   Never
20 (25)
8 (20)
ECOG PS, n (%)
   0
65 (82)
31 (76)
   1
14 (18)
10 (24)
Reasons for not receiving NAC, n (%)
   Ineligible
31 (39)
15 (37)
      GFR <60 mL/min
19 (24)
10 (24)
      Audiometric hearing loss (CTCAE grade ≥2)
8 (10)
2 (5)
      Peripheral neuropathy (CTCAE grade ≥2)
3 (4)
3 (7)
      Other
1 (1)
0
   Declined
48 (61)
26 (63)
      Quality of life
29 (37)
24 (59)
      Age
9 (11)
1 (2)
      Patient comorbidity
3 (4)
1 (2)
      Patient decision
3 (4)
0
      Other
4 (5)
0
Residual disease (visibly incomplete TURBT), n (%)
16 (20)
6 (15)
Tumor stage, n (%)
   cT2
62 (78)
35 (85)
   cT3-4a
17 (22)
6 (15)
Urothelial carcinoma with variant histology, n (%)
16 (20)
11 (27)
Prior intravesical therapy, n (%)
10 (13)
8 (20)
Abbreviations: CTCAE, Common Terminology Criteria for Adverse Events; cTNM, clinical stage-primary tumor [T], lymph node [N], distant metastasis [M]; ECOG PS, Eastern Cooperative Oncology Group performance status; GFR, Glomerular filtration rate; NAC, neoadjuvant cisplatin-based chemotherapy; SD, standard deviation; TURBT, transurethral resection of bladder tumor.
Efficacy
  • The efficacy-evaluable population was comprised of patients who had adequate RC results or who had progression or death before undergoing RC (INLEXZO + cetrelimab, 67%, 53/79; cetrelimab monotherapy, 76%, 31/41). 
    • Overall, 14 patients had not received RC at the clinical cutoff, due to progressive disease (INLEXZO + cetrelimab cohort, n=1; cetrelimab monotherapy, n=4), withdrawing consent (INLEXZO + cetrelimab cohort, n=3; cetrelimab monotherapy, n=1), death (INLEXZO + cetrelimab cohort, n=2; cetrelimab monotherapy, n=1), receiving RC after the clinical cutoff (INLEXZO + cetrelimab, n=1), or was under pathological review at the time of the clinical cutoff (INLEXZO + cetrelimab, n=1).
  • At a clinical cutoff date of May 31, 2024, and a median follow-up of 23.5 weeks (interquartile range [IQR], 8.6-42.0 weeks), the pCR and pOR rates of the efficacy-evaluable population were reported as summarized in Table: pCR and pOR in the INLEXZO + Cetrelimab (Cohort 1) and Cetrelimab Monotherapy (Cohort 2) Groups.

pCR and pOR in the INLEXZO + Cetrelimab (Cohort 1) and Cetrelimab Monotherapy (Cohort 2) Groups4 

INLEXZO + Cetrelimab
Cohort 1
Cetrelimab Monotherapy
Cohort 2
Efficacy-evaluable population (cT2-cT4a)
53
31
   pCR, % (95% CI)
42 (28-56)
23 (10-41)
   pOR, % (95% CI)
60 (46-74)
35 (19-55)
Abbreviations: CI, confidence interval; cTNM, clinical stage-primary tumor [T], lymph node [N], distant metastasis [M]; pCR, pathologic complete response; pOR, pathologic overall response.
Note: pCR is defined as ypT0N0; pOR is defined as ≤ypT1N0.

Efficacy in the INLEXZO + Cetrelimab (Cohort 1) and Cetrelimab Monotherapy (Cohort 2) Subgroups4 
INLEXZO + Cetrelimab
Cohort 1
Cetrelimab Monotherapy
Cohort 2
Subgroup based on tumor stage
   cT2 subgroup, n
40
26
      pCR, % (95% CI)
48 (32-64)
23 (9-44)
      pOR, % (95% CI)
68 (51-81)
31 (14-52)
   cT3-cT4a subgroup, n
13
5
      pCR, % (95% CI)
23 (5-57)
20 (1-72)
      pOR, % (95% CI)
38 (14-68)
60 (15-95)
Subgroup based on completeness of TURBT
   Visibly incomplete resection (≤3 cm) at TURBT, n
9
4
      pCR, % (95% CI)
56 (21-86)
0 (0-60)
      pOR, % (95% CI)
67 (30-93)
0 (0-60)
   Visibly complete resection at TURBT, n
44
27
      pCR, % (95% CI)
39 (24-55)
26 (11-46)
      pOR, % (95% CI)
59 (43-74)
41 (22-61)
Subgroups based on number of INLEXZO dosesa
   Received 1 or 2 doses of INLEXZO + cetrelimab
11
NA
      pCR, % (95% CI)
27 (6-61)
NA
      pOR, % (95% CI)
46 (17-77)
NA
   Received 3 doses of INLEXZO + cetrelimab
10
NA
      pCR, % (95% CI)
30 (7-65)
NA
      pOR, % (95% CI)
50 (19-81)
NA
   Received 4 doses of INLEXZO + cetrelimab
32
NA
      pCR, % (95% CI)
50 (32-68)
NA
      pOR, % (95% CI)
69 (50-84)
NA
Abbreviations: CI, confidence interval; cTNM, clinical stage-primary tumor [T], lymph node [N], distant metastasis [M]; NA, not applicable; pCR, pathologic complete response; pOR, pathologic overall response; TRAEs, treatment-related adverse events; TURBT, transurethral resection of bladder tumor.
Note: pCR is defined as ypT0N0; pOR is defined as ≤ypT1N0.
aThe subgroup analysis for the number of INLEXZO doses was performed post-hoc.
Safety
  • The safety population was comprised of patients who received at least one dose of any study treatment (n=120; INLEXZO + cetrelimab, n=79; cetrelimab monotherapy, n=41). 
    • Overall, 25% (20/79) of patients in the INLEXZO + cetrelimab cohort and 22% (9/41) of patients in the cetrelimab monotherapy cohort remained on treatment and had not reached the RC window.
  • The median follow-up (post-RC) in both cohorts was 10.2 weeks (IQR, 1.1-36.9). 
  • At the clinical cutoff date of May 31, 2024, the overall safety profiles of INLEXZO + cetrelimab (cohort 1) and cetrelimab monotherapy (cohort 2) were reported as summarized in Table: Overall Safety Profile of the INLEXZO + Cetrelimab (Cohort 1) and Cetrelimab Monotherapy (Cohort 2) Groups.
  • No treatment-emergent or treatment-related deaths occurred in the INLEXZO + cetrelimab cohort. 

Overall Safety Profile of the INLEXZO + Cetrelimab (Cohort 1) and Cetrelimab Monotherapy (Cohort 2) Groups13
Patients With ≥1 Event, n (%)
INLEXZO + Cetrelimab
Cohort 1
(n=79)
Cetrelimab Monotherapy
Cohort 2
(n=41)
AE (any cause)
69 (87.3)
38 (92.7)
   TRAEs
57 (72.2)
18 (43.9)
SAEs
36 (45.6)
13 (31.7)
   Treatment-related SAEs
9 (11.4)
1 (2.4)
Grade ≥3 AEs
38 (48.1)
15 (36.6)
   Grade ≥3 TRAEs
9 (11.4)
2 (4.9)
AEs (any cause) leading to treatment discontinuation
14 (17.7)
0
   TRAEs leading to treatment discontinuationa
10 (12.7)
0
      INLEXZO discontinuation
7 (8.9)
-
      Cetrelimab discontinuation
6 (7.6)
0
AEs (any cause) leading to death
4 (5.1)
2 (4.9)
   TRAEs leading to death
0
1 (2.4)b
Immune-related AEs
29 (36.7)
18 (43.9)
   Grade ≥3 immune-related AEs
5 (6.3)
2 (4.9)
Abbreviations: AE, adverse event; CTCAE, Common Terminology Criteria for Adverse Events; RC, radical cystectomy; SAE, serious adverse events; TRAE, treatment-related adverse event.
aMost frequent TRAE leading to INLEXZO discontinuation was pollakiuria (n=2).
bTRAE leading to death was reported as hyperglycemic hyperosmolar nonketotic syndrome (n=1).
  • A summary of TRAEs are reported in Table: Select TRAEs in INLEXZO + Cetrelimab (Cohort 1) and Cetrelimab Monotherapy (Cohort 2) Groups.
  • Grade 1 or 2 TRAEs were reported in 48/79 (61%) of patients in the INLEXZO + cetrelimab cohort. 
  • The most frequent TRAEs with INLEXZO + cetrelimab were grade 1-2 urinary events.
  • Grade 3 TRAEs occurring in the INLEXZO + cetrelimab cohort included (n=1 each): urinary bladder hemorrhage, blood creatine phosphokinase increased, aphthous ulcer, and urethritis.
  • Grade 4 TRAEs occurring in the INLEXZO + cetrelimab cohort included (n=1 each): diabetic ketoacidosis, immune-mediated arthritis, and neutropenia. No grade 5 TRAEs occurred in the INLEXZO + cetrelimab cohort.
  • One patient treated with cetrelimab monotherapy had an acute kidney injury (grade 4) and died from hyperglycemic hyperosmolar nonketotic syndrome (grade 5). The patient was counted only once under the worst toxicity grade.

Select TRAEs in INLEXZO + Cetrelimab (Cohort 1) and Cetrelimab Monotherapy (Cohort 2) Groups4 
TRAEsa, n (%)
INLEXZO + Cetrelimab
Cohort 1
(n=79)
Cetrelimab Monotherapy
Cohort 2
(n=41)
Overall
(n=120)
Grade 1-2b
Grade 3
Grade 1-2b
Grade 3
Dysuria
22 (28)
0
0
0
22 (28)
Pollakiuria
21 (27)
1 (1)
0
0
22 (18)
Micturition urgency
12 (15)
0
0
0
12 (10)
Hematuria
9 (11)
2 (3)
0
0
11 (9)
Urethral pain
5 (6)
0
0
0
5 (4)
Bladder pain
4 (5)
0
0
0
4 (3)
Bladder spasm
4 (5)
0
0
0
4 (3)
Lipase increased
4 (5)
0
0
1 (2)
5 (4)
Fatigue
6 (8)
1 (1)
3 (7)
0
10 (8)
Asthenia
4 (5)
0
0
0
4 (3)
Diarrhea
2 (3)
0
3 (7)
0
5 (4)
Hyperamylasemia
5 (6)
0
1 (2)
1 (2)
7 (6)
Pruritus
1 (1)
0
4 (10)
0
5 (4)
Urinary tract infection
7 (9)
0
0
0
7 (6)
Hyperthyroidism
6 (8)
0
1 (2)
0
7 (6)
Hypothyroidism
4 (5)
1 (1)
1 (2)
0
6 (5)
Urinary tract pain
2 (3)
1 (1)
0
0
3 (3)
Abbreviations: TRAE, treatment-related adverse event.
aPatients were counted only once for any given event, regardless of the number of times the event occurred. The event with the worst toxicity was used.
bTotal any-grade TRAEs by preferred term occurring in ≥5% of patients in either cohort are reported.
Radical Cystectomy Outcomes
  • The median time to RC was 13.7 weeks (IQR, 12.7-14.6) with INLEXZO + cetrelimab and 12.6 weeks (IQR, 12.0-14.4) with cetrelimab monotherapy. 
  • There were 8 patients who underwent RC beyond week 15 due to scheduling delays and treatment-emergent adverse events (TEAEs), 12 patients who underwent RC at week 11, and 4 patients who underwent RC prior to week 11. 

Psutka et al (2025)6 presented preliminary perioperative outcomes (surgical, laboratory, and safety) for patients with MIBC who received INLEXZO + cetrelimab therapy (cohort 1, n=79) or cetrelimab monotherapy (cohort 2, n=41).

Surgical Outcomes

Perioperative Surgical Outcomes in the INLEXZO + Cetrelimab (Cohort 1) and Cetrelimab Monotherapy (Cohort 2) Groups6
Patients, n (%)
INLEXZO + Cetrelimab
Cohort 1
(n=50)
Cetrelimab Monotherapy
Cohort 2
(n=26)
Method of RC
   Robotic
32 (64.0)
8 (30.8)
   Open
14 (28.0)
15 (57.7)
   Laparoscopic
4 (8.0)
3 (11.5)
Type of urinary diversion
   Incontinent diversions
      Ileal conduit
40 (80.0)
19 (73.1)
      Ureterocutaneostomy
1 (2.0)
0
   Continent diversions
      Neobladder
6 (12.0)
7 (26.9)
      Continent pouch
3 (6.0)
0
Abbreviation: RC, radical cystectomy.

Time to RC in the INLEXZO + Cetrelimab (Cohort 1) and Cetrelimab Monotherapy (Cohort 2) Groups6
Patients, n (%)
INLEXZO + Cetrelimab
Cohort 1
(n=50)
Cetrelimab Monotherapy
Cohort 2
(n=26)
Within protocol-specified window, n (%)
41 (82)
23 (88.5)
   Median time to RC, weeks (range)
13.6 (11.6-15.9)
12.4 (11.1-15.1)
Before protocol-specified window, n (%)
4 (8)
0
   Median time to RC, weeks (range)
8.4 (4.1-10.7)
NA
      PI decision, n (%)
2 (4)
0
      Other, n (%)
1 (2)
0
      Symptomatic progression, n (%)
1 (2)
0
After protocol-specified window, n (%)
5 (10)
3 (11.5)
   Median time to RC, weeks (range)
18.4 (16.0-19.4)
16.1 (12.4-18.0)
      PI decision, n (%)
1 (2)
1 (3.8)
      Other, n (%)
2 (4)
1 (3.8)
      Patient decision, n (%)
2 (4)
0
      Hematuria, n (%)
0
1 (3.8)
Abbreviations: NA, not applicable; PI, principal investigator; RC, radical cystectomy.
  • In INLEXZO + cetrelimab (cohort 1) and cetrelimab monotherapy (cohort 2) groups, there was no ECOG PS worsening in 90.4% (47/52) and 84.6% (22/26) of patients, respectively, when compared at week 6 to baseline.
Safety Outcomes
Post-RC Morbidity and Mortality

Post-RC Morbidity and Mortality (30 and 90 Days) in the INLEXZO + Cetrelimab (Cohort 1) and Cetrelimab Monotherapy (Cohort 2) Groups6
Patients With ≥1 Event, n (%)a
Within 30 Days Post-RC
Within 90 Days Post-RC
Overall
(n=60)
INLEXZO + Cetrelimab
Cohort 1
(n=38)
Cetrelimab Monotherapy
Cohort 2
(n=22)
Overall
(n=38)
INLEXZO + Cetrelimab
Cohort 1
(n=23)
Cetrelimab Monotherapy
Cohort 2
(n=15)
Post-RC Morbidity
   ≥1 TEAE
   any
   grade
48 (80.0)
29 (76.3)
19 (86.4)
31 (81.6)
18 (78.3)
13 (86.7)
   Serious
   TEAE
24 (40.0)
17 (44.7)
7 (31.8)
15 (39.5)
11 (47.8)
4 (26.7)
   Grade
   ≥3 TEAE
25 (41.7)
16 (42.1)
9 (40.9)
15 (39.5)
10 (43.5)
5 (33.3)
Post-RC Mortalityb
   Any
   cause
1 (1.7)
0
1 (4.5)c
2 (5.3)
1 (4.3)d
1 (6.7)c
Abbreviations: RC, radical cystectomy; TEAE, treatment-emergent adverse event.
aPatients who reached 30 or 90 days post-RC.
bNo deaths related to neoadjuvant treatment with INLEXZO or cetrelimab.
cThe cause of mortality was renal failure.
dThe cause of mortality was cardiorespiratory arrest.

Management of Adverse Events Related to INLEXZO in the SunRISe-4 Study

  • Early removal of INLEXZO, dose delays, and dose interruptions of INLEXZO were permitted per protocol to manage adverse events.13  
  • Patients must have received at least one dose of periprocedural prophylactic antibiotics for any INLEXZO insertion and/or removal procedures to mitigate risk of urinary tract infection.13 
  • Anticholinergics, non-steroidal anti-inflammatory drugs, bladder analgesics, and short-course corticosteroids were permitted to treat urinary tract symptoms.13 

Literature SearcH

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 15 October 2025.

 

References

Show
1 Janssen Research & Development, LLC. A phase 2, open-label, multi-center, randomized study of TAR-200 in combination with cetrelimab and cetrelimab alone in participants with muscle-invasive urothelial carcinoma of the bladder who are scheduled for radical cystectomy and are ineligible for or refusing platinum-based neoadjuvant chemotherapy. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 October 15]. Available from: https://clinicaltrials.gov/study/NCT04919512 NLM Identifier: NCT04919512.  
2 Necchi A, Guerrero-Ramos F, Crispen PL, et al. Neoadjuvant gemcitabine intravesical system (TAR-200) + cetrelimab or cetrelimab alone in patients with muscle-invasive bladder cancer: SunRISe-4 primary analysis and biomarker results. Oral Presentation presented at: European Society for Medical Oncology (ESMO) Congress; October 17-21, 2025; Berlin, Germany.  
3 Necchi A, Guerrero-Ramos F, Crispen PL, et al. Neoadjuvant gemcitabine intravesical system (TAR-200) + cetrelimab (CET) or CET alone in patients (pts) with muscle-invasive bladder cancer (MIBC): SunRISe-4 (SR-4) primary analysis and biomarker results. Abstract presented at: European Society for Medical Oncology (ESMO) Congress; October 17-21, 2025; Berlin, Germany.  
4 Necchi A, Guerrero-Ramos F, Crispen PL, et al. TAR-200 plus cetrelimab versus cetrelimab monotherapy as neoadjuvant therapy in patients with muscle-invasive bladder cancer who are ineligible for or decline neoadjuvant cisplatin-based chemotherapy (SunRISe-4): interim analysis of a randomised, open-label phase 2 trial. [published online ahead of print August 27, 2025]. Lancet Oncol. 2025:1-11. doi:10.1016/s1470-2045(25)00358-4.  
5 Psutka SP, Cutie CJ, Bhanvadia SK, et al. SunRISe-4: TAR-200 plus cetrelimab or cetrelimab alone as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or refuse neoadjuvant platinum-based chemotherapy. Poster presented at: American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU); February 16-18, 2023; San Francisco, CA and Virtual.  
6 Psutka S, Herrera-Imbroda B, Crispen P, et al. Perioperative outcomes of neoadjuvant TAR-200 plus cetrelimab or cetrelimab alone in patients with muscle-invasive bladder cancer ineligible for or refusing neoadjuvant cisplatin-based chemotherapy. Oral Presentation presented at: European Association of Urology (EAU) Congress; March 21-24, 2025; Madrid, Spain.  
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10 Daneshmand S, Kamat AM, Shore ND, et al. Development of TAR-200: a novel targeted releasing system designed to provide sustained delivery of gemcitabine for patients with bladder cancer. Urol Oncol. 2025;43(5):286-296.  
11 Daneshmand S, Brummelhuis ISG, Pohar KS, et al. The safety, tolerability, and efficacy of a neoadjuvant gemcitabine intravesical drug delivery system (TAR-200) in muscle-invasive bladder cancer patients: a phase I trial. Urol Oncol. 2022;40(7):344.e1-344.e9.  
12 Daneshmand S, Van der Heijden MS, Jacob JM, et al. TAR-200 for Bacillus Calmette-Guérin-unresponsive high-risk non-muscle-invasive bladder cancer: results from the phase IIb SunRISe-1 study. [published online ahead of print July 30, 2025]. J Clin Oncol. doi:10.1200/jco-25-01651.  
13 Necchi A, Guerrero-Ramos F, Crispen PL, et al. Supplement to: TAR-200 plus cetrelimab versus cetrelimab monotherapy as neoadjuvant therapy in patients with muscle-invasive bladder cancer who are ineligible for or decline neoadjuvant cisplatin-based chemotherapy (SunRISe-4): interim analysis of a randomised, open-label phase 2 trial. [published online ahead of print August 27, 2025]. Lancet Oncol. 2025. doi:10.1016/s1470-2045(25)00358-4.  
14 Grimberg DC, Shah A, Inman BA. Overview of Taris GemRIS, a Novel Drug Delivery System for Bladder Cancer. Eur Urol Focus. 2020;6(4):620-622.