Perioperative Pembrolizumab/Sacituzumab Govitecan for MIBC
Here’s a summary of the key points from the provided text, focusing on the SURE-02 study:
Rationale: SURE-02 was designed to build upon previous studies (PURE study and another SURE-02 study) that evaluated pembrolizumab and sacituzumab govitecan as single agents in MIBC (muscle-invasive bladder cancer). The goal was to investigate the combination of these two drugs in a neoadjuvant setting.
Trial Design and Amendments: The study was initially designed as a perioperative trial (neoadjuvant sacituzumab govitecan + cystectomy + adjuvant pembrolizumab). Though, due to patient preference and deep responses to neoadjuvant therapy, the protocol was amended.The amendment allowed for a multidisciplinary discussion after neoadjuvant treatment, possibly leading to a re-TURBT (transurethral resection of bladder tumor) and maintenance pembrolizumab, thus preserving the bladder. The primary endpoint shifted from pathological complete response (pCR) to clinical complete response (cCR), defined as negative imaging and negative biopsy via TURBT.
Preliminary Efficacy Results: Interim findings (from 49 patients, with 13 still awaiting primary endpoint results) showed a promising cCR rate of 44.1%. Patients who kept their bladder and underwent re-TURBT were metastasis-free at the last follow-up, with only 2 intravesical relapses. The metastasis-free survival rate in complete responders was 100%.
Initial Biomarker Data:
Patients with luminal subtype tumors were more likely to respond to treatment, suggesting sacituzumab govitecan’s contribution in overcoming immunotherapy resistance typically associated with this subtype.
Higher levels of TROP-2 expression were associated with a flat event-free survival curve.
ARID1A mutations were observed.
TROP-2 expression in complete responders was enriched in the luminal subtype.
Higher tumor mutational burden was associated with higher responses.
These are the first presented biomarker data associated with a TROP-2-directed antibody-drug conjugate (ADC).