SUMMARY

• SunRISe-1 (NCT04640623) is an ongoing, phase 2b, randomized, open-label, multicenter study evaluating the efficacy and safety of intravesical TAR-200 plus systemic cetrelimab, an investigational immunoglobulin G4 (IgG4) antibody that targets the programmed cell death protein-1 (PD-1) receptor, TAR-200 alone, or cetrelimab alone in patients with high‑risk, non-muscle-invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette–Guérin (BCG) who are ineligible for or decline radical cystectomy (RC). The primary endpoint is overall complete response (CR) rate. Enrollment is planned for approximately 200 patients in 122 global study locations.^1,2
• Daneshmand et al (2023)³ reported first results for 47 patients with high-risk NMIBC who received treatment with TAR-200 alone (cohort 2) or cetrelimab alone (cohort 3) have been reported.
  • Of the 22 evaluable patients who received TAR-200 alone, 16 patients (72.7%; 95% confidence interval [CI], 49.8-89.3) achieved CR. After a median follow-up of 10.6 months with TAR-200, 15 of 16 responses are ongoing. Median duration of response (DOR) was not reached.
  • Among patients receiving TAR-200 alone, 1 patient had serious treatment-related adverse events (TRAEs) and 2 patients had grade ≥3 TRAEs. Most treatment-emergent adverse events reported were grade ≤2.
• Jacob et al (2024)⁴ reported updated results for 85 patients with high-risk NMIBC who received treatment with TAR-200 alone (cohort 2).
  • Of the 58 centrally-assessed and 58 investigator-assessed patients who received TAR-200 alone, 48 patients (82.8%; 95% CI, 70.6-91.4) and 50 patients (86.2%; 95% CI, 74.6-93.9), respectively, achieved CR. After a median follow-up of 29.9 weeks with TAR200 alone, CR was ongoing in 41 of 48 (85%) patients. The 18-month DOR was 74.6% (95% CI, 49.8-88.4). Four of five patients (80%) who completed 2 years of treatment continue to respond at the time of this analysis. One of 48 complete responders has undergone RC.
  • Of all patients (n=85), 4 patients (4.7%) had ≥1 adverse events (AEs) leading to TAR200 discontinuation, 4 patients (4.7%) had ≥1 serious TRAEs, and 7 patients (8.2%) had grade ≥3 TRAEs. Most AEs reported were grade ≤2. No treatment-related deaths were reported.
• van der Heijden et al (2024)⁵ reported results from TAR-200 + cetrelimab (cohort 1), TAR-200 alone (cohort 2), and cetrelimab alone (cohort 3).
  • The overall centrally-assessed CR rate in patients who received TAR-200 + cetrelimab (n=53) at any time was found to be 67.9% (95% CI, 53.7-80.1).
  • The overall centrally-assessed CR rate in patients who received TAR-200 alone (n=85) at any time was found to be 83.5% (95% CI, 73.9-90.7).
  • The overall centrally-assessed CR rate in patients who received cetrelimab alone (n=28) at any time was found to be 46.4% (95% CI, 27.5-66.1).
  • Overall, most AEs were grade 1 or 2 at the time of this analysis.
  • Higher rates of grade ≥3 TRAEs were observed with TAR-200 + cetrelimab regimen (35.8%) than with TAR-200 (9.4%) or cetrelimab (7.1%) alone.
  • Daneshmand et al (2024)⁶ reported additional tolerability and safety in the TAR-200 alone group (cohort 2), including insertion success rate (98.8%) and indwelling duration (median, 22 days; range 5-26 days).
• Xylinas et al (2024)⁷ reported the results from an exploratory analysis, in which the association of the response of TAR-200 alone (cohort 2) was evaluated with PD-L1 expression, tumor mutational burden, and microsatellite instability.

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 through the prescribed indwelling period.^1,8-10
• 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.⁹

CLINICAL DATA

SunRISe-1 Study

SunRISe-1 is in ongoing study designed to assess the efficacy and safety of intravesical TAR-200 plus cetrelimab (cohort 1), TAR-200 alone (cohort 2 and 4), or cetrelimab alone (cohort 3) in patients with high‑risk NMIBC unresponsive to BCG who are ineligible for or decline RC.^1,2

Study Design/Methods

• Phase 2b, ongoing, randomized, open-label, multicenter study.
• The study design is shown in Figure: SunRISe-1 Study Design.
• Primary endpoint: Overall CR rate as determined by cystoscopy, central cytology, and central pathology at weeks 24 and 48; imaging was performed at weeks 24 and 48.³
• Key secondary endpoints: DOR, overall survival (OS), pharmacokinetics (PK), health-related quality of life (HRQoL), and safety and tolerability.³

Results

Patient Characteristics

• At a clinical cutoff date of April 4, 2023, the characteristics of 23 patients from the TAR-200 alone group were reported as described in Table: Patient Characteristics in TAR-200 Alone Group.
• Baseline characteristics were well-balanced between groups.

• At a clinical cutoff date of January 2, 2024, the patient characteristics of 85 patients from the TAR-200 alone group were reported as described in Table: Updated Patient Characteristics in TAR-200 Alone Group.

• At a clinical cutoff date of May 13, 2024, the patient characteristics of the TAR-200 + cetrelimab, TAR-200 monotherapy, and cetrelimab alone groups were reported as described in Table: Updated Patient Characteristics in TAR-200 + Cetrelimab (Cohort 1), TAR-200 Alone (Cohort 2), and Cetrelimab Alone (Cohort 3).

Efficacy

• The efficacy analysis was performed on all treated patients who have active disease at baseline and adequate disease assessment post-baseline, or who have progressed, died due to recurrence of HR disease or progressive disease, or have discontinued the study.
• At a clinical cutoff date of April 4, 2023³:
  • Of the 22 evaluable patients who received treatment with TAR-200 alone, 16 patients (72.7%; 95% CI, 49.8-89.3) achieved CR.
  • After median follow-up of 10.6 months with TAR-200 alone, 15 of 16 responses are ongoing (median DOR was not reached). Six complete responders maintained their response beyond 12 months. None of the complete responders have documented recurrence or progression.
• At a clinical cutoff date of January 2, 2024⁴:
  • Of the 58 centrally-assessed and 58 investigator-assessed patients who received TAR-200 alone, 48 patients (82.8%; 95% CI, 70.6-91.4) and 50 patients (86.2%; 95% CI, 74.6-93.9) respectively achieved CR.
  • After a median follow-up of 29.9 weeks with TAR200 alone, CR was ongoing in 41 of 48 patients. The 18-month DOR was 74.6% (95% CI, 49.8-88.4). Four of five patients (80%) who completed 2 years of treatment continue to respond at the time of this analysis. One of 48 complete responders have undergone RC.
• At a clinical cutoff date of May 13, 2024⁵:
  • The overall CR rate assessed at any time in each treatment group is summarized in Table: Overall CR Rate in TAR-200 + Cetrelimab (Cohort 1), TAR-200 Alone (Cohort 2), and Cetrelimab Alone (Cohort 3).

• The complete response rate and duration of response in each treatment group are summarized in Table: Complete Response Rate and Duration of Response in TAR-200 + Cetrelimab (Cohort 1), TAR-200 Alone (Cohort 2), and Cetrelimab Alone (Cohort 3).

Insertion and Indwelling

• The TAR-200 insertion success rate was 98.8%, and the median indwelling duration was 22 days (range, 5-26).⁶ 

Safety

• At a clinical cutoff date of April 4, 2023, the overall safety profile of the TAR-200 and cetrelimab alone groups is summarized in Table: Overall Safety Profile of the TAR-200 and Cetrelimab Alone Groups.
  • Among patients receiving TAR-200 alone, 1 patient had a serious TRAE (resolved renal impairment and urosepsis) and 2 patients had grade ≥3 TRAEs.
  • 8.7% of patients discontinued TAR-200 due to TRAEs. No deaths were observed.

• At a clinical cutoff date of January 2, 2024, the overall updated safety profile of the TAR-200 alone group is summarized in Table: Overall Updated Safety Profile of the TAR-200 Alone Group.
  • Of all patients (n=85), 4 patients (4.7%) had ≥1 AEs leading to TAR200 discontinuation, 4 patients (4.7%) had ≥1 serious TRAEs, and 7 patients (8.2%) had grade ≥3 TRAEs. No treatment-related deaths were observed.

• At a clinical cutoff date of May 13, 2024, the overall safety profile of patients in all three groups is summarized in Table: Overall Safety Profile of TAR-200 + Cetrelimab (Cohort 1), TAR-200 Alone (Cohort 2), and Cetrelimab Alone (Cohort 3).

• The proportions of patients with serious TRAEs are as follows:
  • TAR-200 + cetrelimab (cohort 1): 13.2%
  • TAR-200 (cohort 2): 5.9%
  • Cetrelimab (cohort 3): 3.6%
• Grade 3/4 TRAEs included 9.4% of patients in TAR-200 alone (cohort 2).⁶ 
• The discontinuation rates due to TRAEs:
  • TAR-200 + cetrelimab (cohort 1): TAR-200, 26.4%; cetrelimab, 22.6%
  • TAR-200 alone (cohort 2): 5.9%
  • Cetrelimab alone (cohort 3): 7.1%
• The most frequent TRAEs leading to discontinuation:
  • TAR-200 + cetrelimab (cohort 1): bladder pain (n=6); pollakiuria (n=3); and bladder irritation, bladder spasm, urinary incontinence, arthritis, pelvic pain, and pneumonitis (n=2 each)
  • TAR-200 alone (cohort 2): noninfective cystitis (n=3), dysuria (n=1), pollakiuria (n=1), and urinary retention (n=1)
  • Cetrelimab alone (cohort 3): neutropenia (n=1) and myopericarditis (n=1)
  • Note, patients who discontinued in cohort 1 and 2 may have had ≥1 TRAE.
• No treatment-related deaths were reported.

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 02 December 2024.