Background: Standard treatment for muscle invasive bladder cancer (MIBC) is radical cystectomy (RC) and administration of NAC in patients who are eligible to receive cisplatin. Approximately 50% of patients are ineligible to receive cisplatin as a result of pre-existing contraindications, and some refuse to receive any chemotherapy due to concerns of toxicities. Immune checkpoint inhibitors (ICIs) have been shown to be highly active in metastatic urothelial cancer. APL-1202 (nitroxoline) is a reversible and orally available MetAP2 inhibitor with anti-angiogenic and anti-tumor activities. Synergistic effects of APL-1202 and ICIs have been shown in model systems of bladder cancer. It is hypothesized that APL-1202 in combination with tislelizumab, a humanized IgG4 anti-PD-1 MAb, may be an effective neoadjuvant therapy in MIBC. This trial will evaluate the safety, efficacy, and pharmacodynamic effects of APL-1202 in combination with tislelizumab as neoadjuvant therapy for patients with MIBC who are cisplatin ineligible or refuse cisplatin-based chemotherapy. Methods: ANTICIPATE is an open-label, multi-center clinical trial enrolling 79 patients in two phases: Phase Ⅰ and Phase Ⅱ. Phase I is a dose escalation study to determine MTD (maximum tolerated dose) and/or RP2D. Phase II is an expanded proof-of-concept study to evaluate the safety and efficacy of APL-1202 in combination with tislelizumab compared to tislelizumab alone as neoadjuvant therapy for MIBC as measured by pathological complete response (pCR). Phase Ⅰ and Phase Ⅱ both are divided into 3 periods: screening period of 4 weeks, neoadjuvant therapy comprising 3 cycles (each 21 days) prior to radical cystectomy; and a follow-up period of up to 90 days after surgery. The phase Ⅰ will determine the RP2D of APL-1202 in combination with tislelizumab as neoadjuvant therapy for MIBC. Eligible patients have newly diagnosed MIBC and are cisplatin ineligible or refuse cisplatin-based NAC and are planned for RC. In phase Ⅰ, a standard 3+3 dose-escalation design will be used. On day 1 of each cycle, a single dose of 200 mg tislelizumab will be administered intravenously. The daily dose APL-1202 will be escalated in successive cohorts (375 mg à 750 mg à 1,125 mg). The DLT observation window for any dose level will be treatment cycle 1. There will be no intra-patient dose escalation. In phase II patients will be randomly assigned to group 1 (APL-1202 + tislelizumab) or group 2 (tislelizumab only), stratified by PD-L1 expression. The IND has been approved by FDA and NMPA, and the study execution is under preparation both in US and China. Clinical trial information: NCT04813107.