Oral APL-1202 shows promise for MIBC in phase 2 trial

An interim analysis of the phase 2 ANTICIPATE trial (NCT04813107) showed positive results with oral APL-1202 in combination with the PD-1 inhibitor tislelizumab compared with tislelizumab alone in patients with muscle-invasive bladder cancer (MIBC), announced Asieris Pharmaceuticals in a news release.¹

Detailed results from the ANTICIPATE trial are expected to be presented at an upcoming academic meeting.

Asieris Pharmaceuticals, the developer of the investigational oral agent APL-1202, explained in a previous news 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.

The multicenter, open-label phase 1/2 ANTICIPATE trial³ planned to enroll 79 patients newly diagnosed with MIBC who are planning to receive radical cystectomy and are cisplatin ineligible or refuse to receive cisplatin-based neoadjuvant chemotherapy. The study 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. Investigators observed no dose-limiting toxicities in phase 1 of the trial, and they established a recommended dosage level of 1125 mg daily for phase 2.

In phase 2, patients were randomly assigned to receive APL-1202 at the recommended phase 2 dose level (1125 mg) in combination with 200 mg tislelizumab (n = 18) or to 200 mg tislelizumab alone (n = 14) in 3 cycles occurring every 3 weeks. The primary end point for phase 2 of the trial is the pathological complete response rate, which was defined as no microscopic evidence of residual tumor lesions in the bladder determined through histopathological evaluation following surgery.

Asieris explained in the news release that phase 2 of the trial is being conducted in 2 stages based on Simon’s two-stage optimal design. To move out of the first stage, at least 5 of 18 patients in the combination arm and 3 of 14 patients in the monotherapy arm must achieve pathological complete response. Both groups have now met the efficacy criteria in the first stage and will proceed to stage 2.

"This [is a] promising outcome demonstrating the potential of APL-1202 in combination with tislelizumab as neoadjuvant therapy for MIBC. We look forward to the potential of this combination therapy for MIBC patients,” said Linda Wu, PhD, the Chief Development Officer of Asieris, in the news release.¹

APL-1202 is continuing to be explored in the ongoing phase 2/3 clinical trials of combination APL-1202 with intravesical chemotherapy for intermediate- and high-risk patients with NMIBC who relapsed with chemotherapy and APL-1202 as a monotherapy for naïve intermediate-risk patients with NMIBC.

Detailed results from the ANTICIPATE trial are expected to be presented at an upcoming academic meeting.

References

1. Asieris announces positive interim analysis results in phase II clinical trial of oral APL-1202 in combination with tislelizumab, a PD-1 inhibitor, as neoadjuvant therapy for muscle invasive bladder cancer. News release. Asieris Pharmaceuticals. September 13, 2023. Accessed September 14, 2023. https://www.prnewswire.com/news-releases/asieris-announces-positive-interim-analysis-results-in-phase-ii-clinical-trial-of-oral-apl-1202-in-combination-with-tislelizumab-a-pd-1-inhibitor-as-neoadjuvant-therapy-for-muscle-invasive-bladder-cancer-301926149.html

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. News release. Asieris Pharmaceuticals. Published online May 27, 2022. Accessed September 14, 2023. https://asieris.com/asieris-to-present-a-study-protocol-of-apl-1202-in-combination-with-beigenes-tislelizumab-as-neoadjuvant-therapynacfor-muscle-invasive-bladder-cancer-mibc-patients-at-2022/

3. National Institutes of Health US National Library of Medicine 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). Last updated February 22, 2022. Accessed September 14, 2023. https://clinicaltrials.gov/study/NCT04813107