Cyclacel announces Phase 1 sapacitabine, seliciclib data at AACR

Cyclacel Pharmaceuticals announced Phase 1 clinical data from the company’s DNA damage response program with an oral, sequential regimen of sapacitabine and seliciclib as a treatment in patients with BRCA mutant metastatic breast cancer. Data from the study was presented at the American Association for Cancer Research, or AACR and demonstrated that the regimen was safe and led to a clinical benefit rate of 30%. All eight PARP inhibitor naive patients, half of the patients previously treated with platinum agents and one on previous PARP inhibitor responded. Progression on previous platinum or PARP inhibitors was associated with lack of benefit. Both sapacitabine and PARP inhibitors are more effective in cancer cells with BRCA mutations or other homologous recombination repair deficiencies. Based on these data, the investigators are enrolling a Phase 1b/2 study of sapacitabine in combination with a PARP inhibitor in PARP inhibitor-naive patients with BRCA mutant breast cancer. The study evaluated an oral, sequential regimen of sapacitabine, a nucleoside analog prodrug, and seliciclib, a first generation CDK2/9 inhibitor, in patients with metastatic breast cancer harboring BRCA1/2 mutations. Patients received seven days of sapacitabine followed by three days of seliciclib. Of 20 patients treated, six progressed on prior platinum therapy and seven on prior PARP inhibitor. Two patients achieved confirmed progressed response, or PR, and four SD of at least 6 months duration for an overall clinical benefit rate of 30%. Of the two patients achieving PR, one progressed previously on platinum treatment and one had received no prior platinum or PARP inhibitor. Responses occurred in 12 patients. The most frequent grade 3 adverse events were neutropenia, AST/ALT elevation and rash. The only grade 4 adverse events were neutropenia in two patients. Progression on previous platinum agents or PARP inhibitors was associated with lack of benefit, putatively associated in some cases with BRCA reversion alterations.

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