2009P - PUNCH02: Primary results from a phase II study of tislelizumab combined with disitamab vedotin as a bladder preservation therapy for urine tumor DNA (utDNA)-defined clinical complete response (cCR) MIBC patients

Background

Disitamab vedotin (RC48) was a novel antibody drug conjugate that targets the Her2 protein. The phase II study was conducted to evaluate the efficacy and safety of tislelizumab combined with RC48 as a bladder preservation therapy for utDNA-defined cCR MIBC patients (pts).

Methods

The study enrolled pts with cT2-4aN0M0 were diagnosed Her2-positive (IHC 2+ or 3+). Firstly, pts received maximal TURBT, then received tislelizumab (200 mg, Q3W, 4 cycles) and RC48 (2.0 mg/kg, Q2W, 4 cycles). Pts who achieved cCR considered bladder preservation and non-cCR pts underwent cystectomy. cCR was defined as normal urine cytology and MRI imaging, bladder biopsies≤cTa. Secondly, the cCR pts further received utDNA testing. cCR pts who were negative for utDNA proceeded bladder preservation, who were positive for utDNA proceeded bladder preservation or cystectomy according to pt's will. Finally, all pts received tislelizumab combined with RC48 for one year followed by surveillance. The primary endpoint was utDNA-defined cCR rate (defined as cCR and negative for utDNA). Secondary endpoints were bladder-preservation rate and safety.

Results

By Mar. 2024, 10 pts were enrolled and analyzed (male 70%; median age 66.6 (39-75)). cT2=80%, cT3=20%, Her2（2+）=30%, Her2（3+）=70%, Single tumor=30%. 100% pts received maximal TURBT. The median number of tislelizumab and RC48 cycles were 4 (4-4) and 4 (4-4), respectively. Median follow up was 5.7 months (3.2-12.7). The utDNA-defined cCR rate was 70.0% (95% CI, 21.7%-80.7%). One cCR pt was positive for utDNA and opted for bladder preservation. The utDNA-defined cCR rate was 100.0% (95% CI, 100%-100%) for Her2（3+）pts. The utDNA-defined cCR rate was 100.0% (95% CI, 100%-100%) for single tumor pts. During follow-up, the bladder-preservation rate for utDNA-defined cCR pts was 100% (95%CI, 100%-100%). The treatment-related adverse events included a poor appetite (n=1, G1), mouth ulcer (n=1, G2), rash (n=1, G1), alopecia (n=1, G1), numbness in hands and feet (n=2, G2).

Conclusions

Tislelizumab combined with RC48 demonstrated the efficacy and safety in utDNA-defined cCR pts for precise bladder preservation treatment.

Clinical trial identification

ChiCTR2400080073.

Editorial acknowledgement

Legal entity responsible for the study

The First Affiliated Hospital, Sun Yat-sen University, The Urology Department.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.