(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 30th and June 3rd, 2025, was host to a kidney and bladder cancers poster session. Dr. Yuke Chen presented the results of a phase I/II trial of the IL-15RαFc superagonist SHR-1501 +/- BCG for high-risk non-muscle invasive bladder cancer (NMIBC).
Adjuvant intravesical BCG remains the standard of care therapy for select patients with intermediate- and high-risk NMIBC following TURBT. IL-15 agonists can enhance the immune response induced by BCG via stimulating the proliferation and activation of natural killer (NK) cells and CD8+ cytotoxic T cells, without inducing the proliferation of regulatory T cells. SHR-1501 is an IL-15 agonist fusion protein, composed of a humanized antibody Fc region fused with IL-15 and the IL-15Rα sushi domain. In this study, Dr. Chen and colleagues evaluated SHR-1501 in high-risk NMIBC patients.
This phase I/II study included phase 1a and 1b dose escalation components evaluating SHR-1501 alone (at increasing doses from 200 to 600 µg) or in combination with BCG in high-risk NMIBC patients, followed by a phase 2 part of SHR-1501 plus BCG in multiple cohorts:
- Cohort A: BCG-naïve NMIBC
- Cohort B: BCG-unresponsive NMIBC (CIS +/- papillary disease)
- Cohort C: BCG-unresponsive papillary disease (no CIS)
All study patients received the intravesical treatments weekly for 6 weeks during the induction period. During the maintenance period, instillations occurred weekly for the first 3 weeks at 3, 6, 12, 18, and 24 months after the initial induction instillation.
The primary endpoints were as follows:
- Phase 1a and 1b: Dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and recommended phase 2 dose
- Phase 2: Complete response (CR) rate for Cohort B; 12 months disease-free survival rate for Cohorts A and C
As of February 28, 2025, 99 patients were enrolled (Phase 1a, n=8; Phase 1b, n=6, Phase 2, n=30, 25, and 30 in Cohorts A, B, and C, respectively). The baseline characteristics are summarized below:
With regards to safety and tolerability – in the phase 1a, evaluating increasing doses of SHR-1501 alone (200, 400, and 600 µg), and phase 1b part of SHR-1501 + BCG, no DLTs were observed, and the MTD was not reached. Thus, the recommended phase 2 dose was 600 µg of SHR-1501 + 120 mg of BCG.
Grade 3 or worse treatment-related adverse events (TRAEs) were reported in 1 patient (12.5%) receiving SHR-1501 alone (urinary tract infection) and in 13 (14.3%) patients receiving SHR-1501 + BCG.
No serious TRAEs were reported in patients treated with SHR-1501 alone. Two (2.2%) patients with SHR-1501 + BCG had serious TRAEs (urinary tract infection and hematuria). There were no treatment-related deaths.
The 3- and 6-months CR rates in the efficacy-evaluable patients in Cohort B were 84% (16/19) and 83% (10/12), respectively. Of the 16 patients who achieved a CR, a maintained CR was observed at 6 and 9 months in 82% and 72% of patients, respectively.
Among the 35 BCG-naïve NMIBC patients, the 12 months DFS rate was 93%. Conversely, among the 31 patients with BCG-unresponsive Ta/T1 NMIBC without CIS, the 9 months DFS rate was 68%.
Dr. Chen concluded that SHR-1501 monotherapy or in combination with BCG was well-tolerated and demonstrated favorable efficacy in both BCG-naive and BCG-unresponsive, high-risk NMIBC patients, supporting further investigations of this agent.
Presented by: Yuke Chen, Department of Urology, Peking University First Hospital, Beijing, China.
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.