135O - A multi-center phase Ib/II study of RC48-ADC combined with tislelizumab as neoadjuvant treatment in patients with HER2 positive locally advanced MIBC

Background

Bladder cancer with HER2 high expression is related to pathological malignancy and poor prognosis. The standard care for muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy. For HER2 positive MIBC, the efficacy of cisplatin- based NAC are unsatisfied. This study aims to evaluate the safety and efficacy of RC48-ADC, an anti-HER2 antibody conjugation, and tislelizumab as a novel neoadjuvant treatment in this population.

Methods

The enrollment of this Ib/II, multi-center,study are 51 patients with cT2-4bN0-3M0-1a pathological and imaging diagnosed HER2 positive (Immunohistochemistry status 3+ or 2+ or 1+) MIBC. Of them, 6 patients are enrolled in the dose-escalation phase, and 45 patients enter into phase II study (the expected phase II dose for RC48-ADC is 2.0mg/kg). RC48-ADC is given every 2 weeks with a maximum dose of 120mg, and tislelizumab is given every three weeks at the dose of 200mg. Treatment efficacy will be performed by computed imaging and transurethral resection of tumors 4 months later. Patients will receive radical cystectomy or bladder-sparing therapies as their will after neoadjuvant treatment. The primary endpoints are clinical complete remission rate (cCR, T0/Ta/Tis), pathological complete remission rate (PCR) and safety.

Results

Until now, 6 patients are included, and the enrollment is currently ongoing. The median age is 62 years old. Of them, 5 patients are HER2(2+), and 1 patient is HER2(1+). The clinical stages are T3-4aN0-3M0. Four patients have the primary efficacy evaluation by now. Three patients are T0, and 1 patient is Tis. Hence the cCR rate is 100%. One patient suffered from immune-related adverse event, namely, Grade 2 myositis and Grade 1 elevated transaminase, which led to treatment interruption. And 3 patients experienced RC48-ADC related toxicities, including Grade 1 elevated transaminase, Grade 1 erythra and Grade 1 paresthesia. No treatment related dose reduction happened.

Conclusions

Neoadjuvant RC48-ADC combined with tislelizumab in patients with HER2 positive locally advanced MIBC initially shows satisfied efficacy and manageable toxicities, which will be verified by the final analysis.

Clinical trial identification

West China Hospital, Sichuan University (2022(546)) and Release Date (May 9th, 2022).

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.