Perioperative Sacituzumab Govitecan Plus Pembrolizumab Is Safe, Active in MIBC

Muscle-Invasive Bladder Cancer
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Perioperative treatment with the combination of sacituzumab govitecan-hziy (Trodelvy) and pembrolizumab (Keytruda) produced complete responses (CRs) with a manageable safety profile in patients with muscle-invasive bladder cancer (MIBC), according to interim findings from the phase 2 SURE-02 trial (NCT05535218) presented at the 2025 ASCO Annual Meeting.

“We have increasing concerns from patients when they achieve a clinical CR response to treatment, with regards to the need to undergo radical cystectomy,” Andrea Necchi, MD, explained during the presentation. “SURE-02 was designed, or redesigned, to keep the momentum of saving the bladder depending on the response to treatment in these patients.”

For the study, patients underwent 4 cycles of 200 mg pembrolizumab on day 1 and 7.5 mg/kg of sacituzumab govitecan on day 1 and 8 Q3W, followed by post-surgical pembrolizumab for 13 cycles, Q3W. Patients achieving a clinical CR (cCR) were allowed to undergo re-TURBT instead of radical cystectomy, followed by pembrolizumab for 13 cycles, due to a protocol amendment to the trial.

Overall, data showed a cCR rate of 44.4% (95% CI, 27.9% to 61.9%) in the intent-to-treat population (n = 36). The total downstaging rate, including radical cystectomy, was 55.6% at the time of last follow-up.

Further, the 12-month event-free survival (EFS) and metastasis-free survival were 71.3% (95% CI, 55.7% to 91/2%) and 84.2% (95% CI, 72% to 96.5%), respectively. The 12-month bladder intact (BI) EFS in patients who achieved a cCR (n = 16) was 100%. The 12-month BI-EFS in patients who underwent a repeat TURBT (n = 23) was 74% (95% CI, 54.8% to 99%).

In terms of safety, 97.9% (n = 48) of patients experienced a treatment-related adverse event (TRAE), and 46.9% (n = 23) of patients experienced an immune-related AE (irAE). Grade 3-4 TRAEs and irAEs occurred in 18.4% of patients (n = 9) and 4.1% of patients (n = 2), respectively.

Serious treatment-related adverse events occurred in 8.2% (n = 4) of patients.

TRAEs led to treatment discontinuation prior to 4 cycles in 3 patients (6.1%). Dose omissions occurred in 3 patients (6.1%), and dose delays were reported in 4 patients (8.2%). There were no instances of dose reduction.

In total, the study included 49 patients, of whom 36 were included in the efficacy analysis. At the time of data report, treatment was ongoing in 10 patients, and 3 patients did not have radical cystectomy/TURBT data available. The median age of participants was 64 years.

The primary end point for the study was cCR, defined as a negative MRI and no residual viable tumor at reTURBT (ypT0). Secondary end points included EFS, MFS, BI-EFS, overall survival, and safety. The trial also included exploratory end points of biomarkers of response, changes in biomarker expression, and microbiome data.

Additional data from SURE-02

In an assessment of cCR based on genomic alterations in baseline TURBT samples, data showed that ERBB2 alterations were more abundant in complete responders; overall, 40% of those with a cCR (n = 15) had an ERBB2 alteration vs 11% on non-complete responders (n = 18).

Necchi also noted, “Conversely, [non]-cCR patients were enriched in MTAP losses and CDKN2A and B losses as compared to the clinical complete response population.”

Transcriptomic data also showed higher cCR rates for patients with Luminal subtypes. Additionally, there was a correlation between EFS and higher TROP2 mRNA expression and mismatch repair signature.

“To make the story consistent, we know, and we had the evidence here, that the TROP2 expression, mismatch repair signature, and ERBB2 expression are all enriched in the Luminal subtype tumor according to Veracyte Decipher classification,” Necchi added.

Overall, the authors noted that the interim results from SURE-02 support further investigation into the sacituzumab govitecan/pembrolizumab combination in MIBC.

Necchi concluded, "Perioperative SGP resulted in 44% cCR, allowing bladder preservation not just including these cCR patients, but in the rest of the patients undergoing reTURBT."

Reference

Necchi A, Jong JD, Proudfoot J, et al. First results of SURE-02: A phase 2 study of neoadjuvant sacituzumab govitecan (SG) plus pembrolizumab (Pembro), followed by response-adapted bladder sparing and adjuvant pembro, in patients with muscle-invasive bladder cancer (MIBC). J Clin Oncol. 2025;43(suppl 16):abstract 4518. doi:10.1200/JCO.2025.43.16_suppl.4518