According to results from a phase 1 dose-escalation study, the optimal dose of SM-1, an oral small-molecule procaspase-3 agonist, is 800 mg for adult patients with recurrent high-grade glioma.

These findings were presented by Mo Li, MD, Sichuan University, Chengdu, China, at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.

Researchers enrolled 27 patients to receive either 450 mg (n = 3), 600 mg (n = 10), or 800 mg (n = 14) of once daily SM-1 plus temozolomide administered on 5 days of every 28-day cycle. Following 6 cycles of combination therapy, patients then received SM-1 monotherapy until disease progression or unacceptable toxicity. Primary end points included safety, objective response rate (ORR), disease control rate, overall survival (OS), and recommended phase 2 dose. 

At safety analysis, no dose-limiting toxicities were reported across treatment dosages. The most common adverse events included lymphopenia (48.1%), leukopenia (33.3%), and thrombocytopenia. No treatment-related deaths occurred. At efficacy analysis, there was 1 complete response and 6 partial responses. The ORR was 29.2% and disease control rate was 50%. Median OS was 19.4 months. The recommended phase 2 dose was 800 mg. 

Updated phase 2 results of 19 evaluable patients who received 800 mg reported 1 complete response, 5 partial responses, and 9 incidences of stable disease. The ORR was 31.6% and the duration of response was 78.9%. SM-1 reached C_max at 3 to 4 hours post-administration and elimination half-life was 17.5 hours. 

As Dr Li concluded, “SM-1 shows favorable safety and tolerability in [recurrent high-grade glioma] patients, demonstrating synergistic efficacy with [temozolomide] alongside promising antitumor activity and survival benefits.”

Source:

Li M, Kang Z, Li W, et al. SM-1 (procaspase-3 agonist) combined with temozolomide for recurrent high-grade glioma: First-in-class trial. Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA27