TAR-200 yields high CR rate in BCG-unresponsive NMIBC

Results from the ongoing SunRISe-1 study (NCT04640623) indicate a complete response (CR) rate of 84% for treatment with TAR-200 in patients with BCG-unresponsive, high-risk non–muscle-invasive bladder cancer (NMIBC) carcinoma in situ (CIS).¹

Michiel van der Heijden, MD, PhD, medical oncologist at the Netherlands Cancer Institute in Amsterdam, presented the results at the 2024 European Society for Medical Oncology Congress in Barcelona, Spain.

In discussing the background for the study, van der Heijden pointed out that several agents have been approved in recent years for the treatment of high-risk NMIBC CIS, including pembrolizumab (Keytruda), nadofaragene firadenovec (Adstiladrin), and nogapendekin alfa inbakicept (Anktiva). He further noted that 12-month complete response rates with these agents are 19%,² 23%,³ and 45%,⁴ respectively.

Michiel van der Heijden, MD, PhD

“TAR-200 is a novel gemcitabine intravesical releasing system designed for sustained, local delivery of chemotherapy in the bladder, and can be placed in an office procedure.^5-7 Cetrelimab is an anti-PD1 agent with an efficacy and safety profile that is consistent with other checkpoint inhibitors,”^8,9 said van der Heijden.

SunRISe-1 is an open-label phase 2b study evaluating TAR-200 plus cetrelimab (cohort 1), TAR-200 monotherapy (cohort 2), and cetrelimab monotherapy (cohort 3), along with a TAR-200 monotherapy cohort consisting only of patients with papillary disease (cohort 4). Patients in cohorts 1-3 were at least 18 years of age with histologically confirmed high-risk NMIBC CIS (with or without papillary disease), ECOG performance status of 0 to 2, persistent or recurrent disease within 12 months of completion of BCG, were unresponsive to BCG and not undergoing radical cystectomy.

The primary end point for cohorts 1-3 was overall CR rate at any time; key secondary end points included duration of response, overall survival, safety, and tolerability. Cohort 4’s primary end point was disease-free survival rate at 12 months.

“As of June 2023, the protocol was amended to close cohorts 1 and 3 and continue enrollment in the TAR-200 monotherapy arm,” van der Heijden said.

Van der Heijden reported that baseline characteristics were similar across cohorts 1-3. 73.6%, 67.1%, and 66.7% of patients in cohorts 1-3, respectively had CIS only, whereas 26.4%, 32.9%, and 33.3% of patients in cohorts 1-3 had CIS plus papillary disease. Regarding cystectomy, 96.2%, 96.5%, and 100% of patients in cohorts 1-3 declined surgery.

Van der Heijden reported centrally assessed CR rates of 67.9% (95% CI, 53.7-80.1), 84% (95% CI, 73.9-90.7), and 46.4% (95% CI, 27.5-66.1) in cohorts 1-3, respectively. In addition, estimated 12-month CR rates were 56.7% (95% CI, 41.2-69.6), 57.4% (40.6-71.0), and 22.8% (8.6-41.1), respectively.

TAR-200 was found to be well tolerated; most adverse events (AEs) were grade 1 or 2. The rate of serious treatment-related AEs was 13.2%, 5.9%, and 3.6% in cohorts 1-3, respectively. Rate of discontinuation due to treatment-related AEs was 5.9% in cohort. In addition, there were no treatment-related deaths reported.

In his concluding remarks, van der Heijden said the results “support the prioritized development of TAR-200 monotherapy in patients with BCG-unresponsive high-risk non–muscle-invasive bladder cancer."

REFERENCES

1. van der Heijden MS, Simone G, Boegemann M, et al. TAR-200 +/- cetrelimab (CET) and CET alone in patients (pts) with bacillus Calmette-Guérin-unresponsive (BCG UR) high-risk non-muscle-invasive bladder cancer (HR NMIBC): Updated results from SunRISe-1 (SR-1). Presented at: 2024 European Society for Medical Oncology Annual Congress. September 13-17, 2024. Barcelona, Spain. Abstract LBA85. https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/session/calendar?q=LBA85

2. Balar AV, Kamat AM, Kulkarni GS, et al. Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol. 2021;22(7):919-930. doi:10.1016/S1470-2045(21)00147-9

3. Adstiladrin prescribing information. Accessed September 15, 2024. https://ferringusa.com/wp-content/uploads/sites/12/2024/08/ADSTILADRIN-USPI-08.2024-CLEAN.pdf

4. Chamie K, Chang SS, Kramolowsky E, et al. IL-15 superagonist NAI in BCG-unresponsive non-muscle-invasive bladder cancer. NEJM Evid. 2023;2(1):EVIDoa2200167. doi:10.1056/EVIDoa2200167

5. 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. doi:10.1016/j.urolonc.2022.02.009

6. Tyson MD, Morris D, Palou J, et al. Safety, tolerability, and preliminary efficacy of TAR-200 in patients with muscle-invasive bladder cancer who refused or were unfit for curative-intent therapy: a phase 1 study. J Urol. 2023;209(5):890-900. doi:10.1097/JU.0000000000003195

7. van Valenburg FJP, van der Heijden AG, Cutie CJ, et al. The Safety, tolerability, and preliminary efficacy of a gemcitabine-releasing intravesical system (TAR-200) in American Urological Association-defined intermediate-risk non-muscle-invasive bladder cancer patients: a phase 1b study. Eur Urol Open Sci. 2024;62:8-15. doi:10.1016/j.euros.2024.01.013

8. DeAngelis N, Ferrante C, Powers G, et al. Discovery and pharmacological characterization of cetrelimab (JNJ-63723283), an anti-programmed cell death protein-1 (PD-1) antibody, in human cancer models. Cancer Chemother Pharmacol. 2022;89(4):515-527. doi:10.1007/s00280-022-04415-5

9. Felip E, Moreno V, Morgensztern D, et al. First-in-human, open-label, phase 1/2 study of the monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor cetrelimab (JNJ-63723283) in patients with advanced cancers. Cancer Chemother Pharmacol. 2022;89(4):499-514. doi:10.1007/s00280-022-04414-6