A phase II prospective, open-label, multi-center, single-arm study of sasanlimab plus sacituzumab govitecan in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) pts: SSANTROP (APRO07-2022).

4596 Background: Radical cystectomy (RC)is the standard treatment forBCG unresponsive high-risk (HR) NMIBC patients (pts). Pembrolizumab (Pem) was approved by the FDA based on Keynote-057 (41% complete response rate (CRR)) and offers a non-surgical option for pts who decline or are ineligible for RC. Nadofaregene firadenovec and Nogapendekin alfa inbakicept have been recently approved in this setting. Sacituzumab govitecan (SG) demonstrated encouraging efficacy and safety in metastatic urothelial cancer (mUC) in the TROPHY-U-01 trial. Combining ADCs with immunotherapy showed promising results in mUC. We hypothesized if the combination of sasanlimab (Sa), a subcutaneous (SC) anti-PD1 agent, and SG would improve the CRR of Pem in BCG-unresponsive NMIBC pts who refuse or are ineligible for RC. Methods: SSANTROP is a phase II study conducted across 18 sites in Spain to assess the CRR at 3 months (mo) of the combination of Sa (5 cy of Sa 300 mg SC on day 1 every 28 days) plus SG (7 cy of SG 10 mg/kg IV on days 1 and every 21 days) in BCG unresponsive HR NMIBC. Pts achieving CR at 3 mo received maintenance therapy: Sa 300 mg SC every 28-day for up to 2 years. Primary endpoint was CRR at 3 mo with plan for percentage of response assessment maintained at 12 and 15 mo. Key eligibility criteria: ECOG PS 0-1, histologically confirmed BCG-unresponsive HR NMIBC, refusal or ineligibility for RC, urothelial carcinoma histology, and no prior anti-PD1/L1 or anti-CTLA-4 therapy. The sample size of 116 pts was calculated to demonstrate a 53% CRR for the combination, based on a Pem historical control of 41% (one-sided alpha 0.05, power 82%). Design was modified to finally include 40 pts based on a change in the treatment landscape of UC. Results: As of January 21, 2025, 59 pts were screened, and 41 initiated treatment and were included in the safety analysis. Among them, 32 (78%) male, median age of 70.6 years (SD 7.8). Types of BCG-unresponsive disease included: persistent/recurrent CIS alone or with recurrent HG Ta/T1 within 12 mo post-BCG (22 pts, 53.7%), recurrent HG Ta/T1 within 6 mo post-BCG (16 pts, 39%), and T1 HG disease at first evaluation post-induction BCG (3 pts, 7.3%). The most common adverse events (AEs) were diarrhea (58.5%), asthenia/fatigue (58.5%), alopecia (41.5%), neutropenia (36.6%), anemia (24.4%) and stomatitis (22%). Most common grade ≥ 3 AEs included neutropenia (9 pts, 22%), febrile neutropenia (5 pts, 12.2%). G-CSF prophylaxis was implemented as of 09/2024. As of 12/2024 and based on 25 evaluable pts, CRR at 3 mo was 68% (17/25). Conclusions: This trial is the first to evaluate the combination of Sa and SG in BCG-unresponsive HR-NMIBC. With preliminary 3 mo CRR of 68%, the safety analysis identified no unexpected concerns, with severe AEs mainly involving neutropenia and febrile neutropenia. No treatment related toxic deaths occurred. Clinical trial information: 2022-002998-28 .