The combination of APL-1202, a reversible and orally available METAP2 inhibitor, with tislelizumab showed promising activity and safety in the neoadjuvant setting among patients with muscle-invasive bladder cancer, according to the phase 1/2 ANTICIPATE study.

These results were first presented by Matt Galsky, MD, Tisch Cancer Institute at Icahn School of Medicine, New York, New York, at the 2024 ASCO GU Cancers Symposium in San Francisco, California.

Dr Galsky and coauthors wrote, “APL-1202 (nitroxoline) is a reversible and orally available MetAP2 inhibitor with anti-angiogenic and anti-tumor activities … APL-1202 and PD-1 antibody combination therapy demonstrates synergistic effects in several model systems of cancer, including bladder cancer.”

In this phase 2 trial, 42 patients with newly diagnosed muscle-invasive bladder cancer intended for radical cystectomy who were cisplatin-ineligible or refused cisplatin-based neoadjuvant chemotherapy (evaluable patients, n = 32) were randomized to receive either APL-1202 plus tislelizumab (n = 18), or tislelizumab alone (n = 14). The primary end point of this study was pathological complete response (pCR). The planned interim analyses would take place after 18 evaluable patients in the combination group and 14 evaluable patients in the tislelizumab group.

Of the evaluable patients, 18/18 underwent radical cystectomy in the combination group and 13/14 in the tislelizumab group. One patient could not undergo radical cystectomy due to disease progression and 10 refused. The pCR was 39% in the combination group and 21% in the tislelizumab alone group. The pCR rates seen in both the combination and the tislelizumab alone group exceeded the necessary thresholds for expansion to stage 2 of the 2-stage design.

The most common grade ≥3 treatment-emergent adverse events were anemia (22.2%) and lymphocyte count decrease (16.7%) in the combination group; and intestinal obstruction (21.4%) in the tislelizumab group. Adverse events led to drug discontinuation in 16.7% of patients in the combination group and 14.3% in the tislelizumab group. There were no treatment-related deaths reported.

Dr Galsky et al concluded, “The activity and safety of neoadjuvant APL-1202 plus tislelizumab support further evaluation of this novel regimen.”

Source:

Galsky MD, Sfakianos JP, Ye D, et al. Oral APL-1202 in combination with tislelizumab as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC): Interim analysis of ANTICIPATE phase II trial. Presented at the 2024 ASCO GU Cancers Symposium; January 25-27, 2024; San Francisco, California. Abstract 534