Neoadjuvant Futibatinib plus Durvalumab in Muscle Invasive Bladder Cancer

Summary:

Bladder cancer is the 6th most common cancer in the US with about 81,000 new cases annually. Approximately 30% of patients present with muscle-invasive bladder cancer (MIBC) and these patients have an increased risk of nodal and distant metastasis. ​The standard of care is cisplatin-based chemotherapy followed by cystectomy (surgery). However, up to 50% of patients are not cisplatin candidates due to comorbidities. For those ineligible for cisplatin, the standard of care is upfront radical cystectomy, but their 5-year survival rate is less than 50%. Therefore, there is an unmet need to develop perioperative treatments for patients with MIBC who are unfit for cisplatin.​ Durvalumab, an immune checkpoint inhibitor (ICI), had a pathological complete response (pCR) rate of 31% but is limited by ICI resistance. ​Thus, there is a great interest to overcome ICI resistance.​ The resistance of bladder cancer to ICIs is mediated through the FGFR protein. Preclinical studies suggest that targeting FGFR can modulate the tumor microenvironment, preventing the inhibition of immune cells. FGFR targeting agents have found success as single agents in select bladder cancer patients.​ This phase II study will assess the pCR rate of neoadjuvant (perioperative) futibatinib (a next generation FGFR targeting drug) in combination with durvalumab (an ICI) in MIBC patients with high amounts of the FGFR protein who are cisplatin ineligible. Futibatinib has been found to be associated with less drug resistance than previous FGFR targeting agents. The trial will be the first study utilizing a FGFR targeting drug plus an ICI in the perioperative setting in patients with MIBC overexpressing FGFR.​

Trial Registration: ClinicalTrials.gov Identifier: NCT06263153