TAR-200
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TAR-200
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TAR-200 - SunRISe-4 Study
Last Updated: 02/03/2025
SUMMARY
- SunRISe-4 (NCT04919512) is an ongoing, phase 2, randomized, open-label, multicenter study evaluating the efficacy and safety of TAR-200 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.1
, 2 - Necchi et al (2024)
3 reported the interim results for patients with MIBC who were randomized to receive either TAR-200 + cetrelimab therapy (cohort 1, n=79) or cetrelimab monotherapy (cohort 2, n=41). - Of the efficacy-evaluable population treated with the combination of TAR-200 + cetrelimab (n=53), the pathologic complete response (pCR) and pathologic overall response (pOR) rates were 42% (95% confidence interval [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 36% (95% CI, 19-55), respectively.
- Patients experiencing ≥1 treatment-related adverse event (TRAE; any grade) were reported in 72.2% (57/79) and 43.9% (18/41) in TAR-200 + cetrelimab and cetrelimab monotherapy, respectively.
- The most frequent TRAEs with TAR-200 + cetrelimab were grade 1-2 urinary events.
- The rate of discontinuation due to TRAEs was 12.7% (10/79) with TAR-200 + cetrelimab.
BACKGROUND
- TAR-200 (JNJ-17000139) is an investigational intravesical system that is designed to provide local release of gemcitabine in the bladder. TAR-200 contains gemcitabine and urea mini tablets within a dual-lumen silicone tube for gradual release of gemcitabine by an osmotic delivery mechanism throughout the prescribed indwelling period.1,4
- 7 - TAR-200 is inserted intravesically via urinary placement catheter, after which it self-coils into a bi-oval shape (see Figure: TAR-200 Intravesical System). Removal of TAR-200 can be achieved using grasping forceps and flexible cystoscopy.5
,7
CLINICAL DATA
SunRISe-4 Study
Study Design/Methods
- Ongoing, phase 2, randomized, open-label, multicenter study designed to assess the efficacy and safety of TAR-200 in combination with systemic cetrelimab, an investigational IgG4 antibody that targets the PD-1 receptor, and systemic cetrelimab alone as neoadjuvant therapy in patients with MIBC who are scheduled for RC and refuse or are ineligible for platinum-based neoadjuvant chemotherapy1,2
- The study design is shown in Figure: SunRISe-4 Study Design.
Abbreviations: CT, computed tomography; 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; ORR, overall response rate; pCR, pathologic complete response; pOR, pathologic overall response; Q12W, every 12 weeks; R, randomization; RC, radical cystectomy; RECIST, Response Evaluation Criteria in Solid Tumors; RFS, recurrence-free survival; TURBT, transurethral resection of bladder tumor.
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Results
Patient Characteristics
- At a clinical cutoff date of May 31, 2024, the patient characteristics of both
cohorts are described in Table: Patient Characteristics in TAR-200 + Cetrelimab (Cohort 1) and Cetrelimab Monotherapy (Cohort 2).
| Characteristics | TAR-200 + Cetrelimab Cohort 1 (n=79) | Cetrelimab Monotherapy Cohort 2 (n=41) |
|---|---|---|
| Age, years, median (range) | 74.0 (54-85) | 68.0 (48-80) |
| Sex, male, n (%) | 68 (86.1) | 34 (82.9) |
| Race, n (%) | ||
| White | 52 (65.8) | 29 (70.7) |
| Asian | 18 (22.8) | 10 (24.4) |
| Other | 9 (11.4) | 2 (4.9) |
| Region, n (%) | ||
| America | 29 (36.7) | 12 (29.3) |
| Asia | 19 (24.1) | 11 (26.8) |
| Western Europe | 31 (39.2) | 18 (43.9) |
| Nicotine use history, n (%) | ||
| Current | 20 (25.3) | 11 (26.8) |
| Former | 39 (49.3) | 22 (53.7) |
| Never | 20 (25.3) | 8 (19.5) |
| ECOG PS 1, n (%) | 14 (17.7) | 10 (24.4) |
| NAC, n (%) | ||
| Ineligible | 31 (39.2) | 15 (36.6) |
| Refusing | 48 (60.8) | 26 (63.4) |
| Residual disease (visibly incomplete TURBT), n (%) | 16 (20.3) | 6 (14.6) |
| Tumor stage, n (%) | ||
| cT2 | 62 (78.5) | 35 (85.4) |
| cT3-4a | 17 (21.5) | 6 (14.6) |
| Urothelial carcinoma with variant histology, n (%) | 16 (20.3) | 11 (26.8) |
| Prior intravesical therapy, n (%) | 10 (12.7) | 8 (19.5) |
| Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; NAC, neoadjuvant cisplatin-based chemotherapy; TURBT, transurethral resection of bladder tumor. | ||
Efficacy
- The efficacy analysis was performed on all treated patients who were RC evaluable or died prior to RC or had disease progression.
- At a clinical cutoff date of May 31, 2024, TAR-200 + cetrelimab therapy showed higher pCR and pOR rates than cetrelimab monotherapy.3
- The pCR and pOR rates of the efficacy-evaluable population for TAR-200 + cetrelimab (cohort 1) and cetrelimab (cohort 2) were reported in Table: pCR and pOR in TAR-200 + Cetrelimab (Cohort 1) and Cetrelimab (Cohort 2).
| TAR-200 + 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) | 36 (19-55) |
| Abbreviations: CI, confidence interval;NA, not applicable; pCR, pathologic complete response; pOR, pathologic overall response; TURBT, transurethral resection of bladder tumorNote: pCR is defined as ypT0N0; pOR is defined as ≤ypT1N0. | ||
- Subgroup efficacy analyses of the efficacy-evaluable population for TAR-200 + cetrelimab (cohort 1) and cetrelimab (cohort 2) were reported in Table: Efficacy in Subgroups of TAR-200 + Cetrelimab (Cohort 1) and Cetrelimab (Cohort 2).
| TAR-200 + 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 (5-54) | 20 (1-72) |
| pOR, % (95% CI) | 39 (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 TAR-200 dose exposure | ||
| Received 1-2 doses of TAR-200 + cetrelimaba | 11 | NA |
| pCR, % (95% CI) | 27 (6-61) | NA |
| pOR, % (95% CI) | 46 (17-77) | NA |
| Received 3 doses of TAR-200 + cetrelimaba | 10 | NA |
| pCR, % (95% CI) | 30 (7-65) | NA |
| pOR, % (95% CI) | 50 (19-81) | NA |
| Received 4 doses of TAR-200 + cetrelimab | 32 | NA |
| pCR, % (95% CI) | 50 (32-68) | NA |
| pOR, % (95% CI) | 69 (50-84) | NA |
| Abbreviations: CI, confidence interval;NA, not applicable; pCR, pathologic complete response; pOR, pathologic overall response; TURBT, transurethral resection of bladder tumor Note: pCR is defined as ypT0N0; pOR is defined as ≤ypT1N0.aPatients with ≤3 doses of TAR-200 may have missed or skipped a dose without discontinuing treatment or may have discontinued treatment due to TRAEs or for any other reason. | ||
Safety
At the clinical cutoff date of May 31, 2024, the overall safety profiles of TAR-200 + cetrelimab (cohort 1) and cetrelimab monotherapy (cohort 2) were summarized in Table: Overall Safety Profile of TAR-200 + Cetrelimab (Cohort 1) and Cetrelimab Monotherapy (Cohort 2).
| Patients With ≥1 Event, n (%)a | TAR-200 + Cetrelimab Cohort 1 (n=79) | Cetrelimab Monotherapy Cohort 2 (n=41) |
|---|---|---|
| ≥1 TRAE (any grade)b | 57 (72.2) | 18 (43.9) |
| Dysuria | 22 (27.8) | 22 (18.3) |
| Pollakiuria | 22 (27.8) | 22 (18.3) |
| Micturition urgency | 12 (15.2) | 12 (10.0) |
| Hematuria | 11 (13.9) | 11 (9.2) |
| Serious TRAEs | 9 (11.4) | 1 (2.4) |
| TRAEs grade ≥3 | 9 (11.4) | 2 (4.9) |
| TRAEs leading to discontinuation | 10 (12.7) | 0 |
| TRAEs leading to TAR-200 discontinuationc | 7 (8.9) | NA |
| TRAEs leading to cetrelimab discontinuationd | 6 (7.6) | 0 |
| TRAEs leading to death | 0 | 1 (2.4)e |
| Abbreviations: AE, adverse event; CTCAE, Common Terminology Criteria for Adverse Events; NA, not applicable; RC, radical cystectomy; TRAE, treatment-related adverse event. aMedian follow-up (post-RC) was 10.2 weeks. AEs were reported using CTCAE v5.0. bTRAEs occurring in ≥10% of patients in either treatment group are listed. cMost frequent TRAE leading to TAR-200 discontinuation was pollakiuria (n=2). dNo TRAE led to cetrelimab discontinuation in ≥2 patients.eTRAE leading to death was reported as hyperglycemic, hyperosmolar nonketotic syndrome (n=1). | ||
- Most frequent TRAEs with TAR-200 + cetrelimab were grade 1-2 urinary events.
- Grade ≥3 immune-related AEs were observed with TAR-200 + cetrelimab (cohort 1; 6.3%) and cetrelimab monotherapy (cohort 2; 4.9%).
- The median time to RC for the TAR-200 + cetrelimab (cohort 1) and cetrelimab monotherapy (cohort 2) was 13.7 weeks and 12.6 weeks, respectively.
Literature SearcH
A literature search of MEDLINE®
References
| 1 | 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. |
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