HTMC0435 plus temozolomide shows preliminary activity in relapsed small-cell lung cancer

A phase Ib/II trial published in BMC Medicine evaluated the oral PARP inhibitor HTMC0435 plus temozolomide in 59 patients with relapsed extensive-stage small-cell lung cancer after one or two previous treatment lines. Primary endpoints concerned dose-limiting toxicity, maximum tolerated dose, recommended phase II dose, and adverse events. Patients received treatment until progression or intolerable toxicity.

No dose-limiting toxicity occurred during phase Ib, and the maximum tolerated dose was not determined. Fifty-five patients received the recommended HTMC0435 dose of 8 mg twice daily, with temozolomide 75 mg/m² on days 1–7 of each 21-day cycle. Grade 3–4 treatment-related adverse events occurred in 33 of 59 patients (55.9%), most commonly neutropenia (39.0%) and leukopenia (30.5%). No treatment-related deaths occurred.

Among 48 efficacy-evaluable patients, 12 responded, giving an objective response rate of 25.0% (95% CI, 13.6–39.6). Median overall survival among the 55 patients treated at the recommended dose was 11.2 months (95% CI, 8.97–13.14).

These findings suggest preliminary antitumor activity but do not establish comparative benefit. Interpretation is limited by the small population, absence of a randomized comparator, and incomplete efficacy evaluability. Randomized validation is needed. Funding included Shanghai Yidian Pharmaceutical Technology Development Co., Ltd., and the National Natural Science Foundation of China; one author was a company employee.