The first patient has been enrolled in a phase 2 trial exploring the combination of the investigational MetAP2 inhibitor APL-1202 and the PD-1 inhibitor tislelizumab as a non-chemotherapy–based neoadjuvant regimen for the treatment of patients with muscular invasive bladder cancer (MIBC).1
Asieris pharmaceuticals, the developer of the investigational oral agent APL-1202, explained in a press release that the standard of care for patients with MIBC is radical cystectomy with bilateral pelvic lymph node dissection, with cisplatin-eligible patients also receiving neoadjuvant chemotherapy.2 However, the company added that about half of these patients are cisplatin-ineligible due to pre-existing contraindications or a refusal to receive chemotherapy, creating an unmet medical need.
Previous research has established a link between APL-1202’s inhibition of MetAP2 with anti-angiogenic and anti-tumor effects. Further, using model systems, investigators have observed synergist activity between APL-1202 and tislelizumab, an immune checkpoint inhibitor manufactured by BeiGene.
This multicenter, open-label phase 2 study (NCT04813107; ANTICIPATE trial) is being conducted in the United States and China and was preceded by a phase 1 dose-escalation component of the trial that was completed in November 2022.
Matthew Galsky, MD, is a principal investigator on the trial, recruiting patients at Mount Sinai Medical Center in New York City. Galsky is a professor of Medicine and director of Genitourinary Medical Oncology at the Icahn School of Medicine, Mount Sinai. He is also the co-director of the Center of Excellence for Bladder Cancer and associate director for translational research at the Tisch Cancer Institute.
The phase 2 study is specifically enrolling patients with histopathologically confirmed transitional cell carcinoma of the bladder. Patients having mixed histologies must have a dominant (ie, more than 50%) transitional cell pattern. Patients should be recommended for radical cystectomy and be contraindicated to or refuse to receive cisplatin-based chemotherapy in the neoadjuvant setting.3
The target enrollment goal is 79 patients. Enrolled patients will be randomized to the experimental arm of APL-1202 plus tislelizumab or the control arm of tislelizumab alone. The primary efficacy end point is pathologic complete response rate and the primary safety measures are adverse events and serious adverse events.3
"APL-1202 in combination with tislelizumab has shown a promising safety profile in the phase I stage of the clinical trial," John Zhuang, Chief Operation Officer at Asieris, stated in a press release.1 "We will further explore the efficacy and safety of the combination in this phase II stage, and continue to make positive progress on the clinical development of the neoadjuvant therapy to address unmet medical needs and benefit more patients."
1. Asieris Enrolled First Patient for its Phase II Clinical Study of Oral APL-1202 in Combination with Tislelizumab, a PD-1 inhibitor, as Neoadjuvant Therapy for Muscle Invasive Bladder Cancer. Published online and accessed December 12, 2022. https://prn.to/3uKsDGk
2. Asieris to present a study protocol of APL-1202 in combination with BeiGene’s tislelizumab as neoadjuvant therapy (NAC) for muscle invasive bladder cancer (MIBC) patients at 2022 ASCO annual meeting. Published online May 27, 2022. Accessed December 12, 2022. https://bit.ly/3uHSDlN
3. ClinicalTrials.gov. A Study to Evaluate the Safety and Efficacy of Oral APL-1202 in Combination With Tislelizumab Compared to Tislelizumab Alone as Neoadjuvant Therapy in Patients With Muscle Invasive Bladder Cancer (ANTICIPATE). NCT04813107. Last updated February 22, 2022. https://clinicaltrials.gov/ct2/show/NCT04813107